E M Oluwagbenga, M Bergman, K M Ajuwon, G S Fraley
The impact of heat stress (HS) on production is intricately linked with feed intake. We investigated the effects of HS on intestines and diencephalic genes in Pekin ducks. One hundred and sixty adult ducks were allocated to two treatment rooms. The control room was maintained at 22°C and the HS room at 35°C for the first 10 h of the day then reduced to 29.5°C. After 3 weeks, 10 hens and 5 drakes were euthanized from each room and jejunum and ileum collected for histology. Brains were collected for gene expression analysis using qRT-PCR. Intestinal morphology data were analyzed with two-way ANOVA and diencephalic gene data were analyzed with Kruskal-Wallis test. There was an increase in villi width in the ileum (p = .0136) and jejunum (p = .0019) of HS hens compared to controls. HS drakes showed a higher crypt depth (CD) in the jejunum (p = .0198) compared to controls. There was an increase in crypt goblet cells (GC) count in the ileum (p = .0169) of HS drakes compared to HS hens. There was higher villi GC count (p = .07) in the jejunum of HS drakes compared to controls. There was an increase in the crypt GC density (p = .0054) in the ileum, not jejunum, of HS drakes compared to HS hens. Further, there were no differences in the proopiomelanocortin gene expression in either sex but there was an increase in the expression of neuropeptide Y (NPY) gene in HS hens (p = .031) only and a decrease in the corticotropin releasing hormone gene in the HS drakes (p = .037) compared to controls. These data show that there are sex differences in the effect of HS on gut morphology while the upregulation in NPY gene may suggest a role in mediating response to chronic HS.
{"title":"Sex differences in intestinal morphology and increase in diencephalic neuropeptide Y gene expression in female but not male Pekin ducks exposed to chronic heat stress.","authors":"E M Oluwagbenga, M Bergman, K M Ajuwon, G S Fraley","doi":"10.1111/jne.13424","DOIUrl":"https://doi.org/10.1111/jne.13424","url":null,"abstract":"<p><p>The impact of heat stress (HS) on production is intricately linked with feed intake. We investigated the effects of HS on intestines and diencephalic genes in Pekin ducks. One hundred and sixty adult ducks were allocated to two treatment rooms. The control room was maintained at 22°C and the HS room at 35°C for the first 10 h of the day then reduced to 29.5°C. After 3 weeks, 10 hens and 5 drakes were euthanized from each room and jejunum and ileum collected for histology. Brains were collected for gene expression analysis using qRT-PCR. Intestinal morphology data were analyzed with two-way ANOVA and diencephalic gene data were analyzed with Kruskal-Wallis test. There was an increase in villi width in the ileum (p = .0136) and jejunum (p = .0019) of HS hens compared to controls. HS drakes showed a higher crypt depth (CD) in the jejunum (p = .0198) compared to controls. There was an increase in crypt goblet cells (GC) count in the ileum (p = .0169) of HS drakes compared to HS hens. There was higher villi GC count (p = .07) in the jejunum of HS drakes compared to controls. There was an increase in the crypt GC density (p = .0054) in the ileum, not jejunum, of HS drakes compared to HS hens. Further, there were no differences in the proopiomelanocortin gene expression in either sex but there was an increase in the expression of neuropeptide Y (NPY) gene in HS hens (p = .031) only and a decrease in the corticotropin releasing hormone gene in the HS drakes (p = .037) compared to controls. These data show that there are sex differences in the effect of HS on gut morphology while the upregulation in NPY gene may suggest a role in mediating response to chronic HS.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13424"},"PeriodicalIF":3.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Sorbye, G. O. Hjortland, L. W. Vestermark, A. Sundlov, J. Assmus, A. Couvelard, A. Perren, S. W. Langer
Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections were pseudonymised before centralized pathological re-evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re-classification: 30 NEC, 12 NET G3, 3 HG-NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP-NEN, all 17 large-cell NEC (100%), 11/13 (85%) small-cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP-NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP-NEN. The NETest was almost always elevated in GEP-NEC and in all large-cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy.
{"title":"NETest in advanced high-grade gastroenteropancreatic neuroendocrine neoplasms","authors":"H. Sorbye, G. O. Hjortland, L. W. Vestermark, A. Sundlov, J. Assmus, A. Couvelard, A. Perren, S. W. Langer","doi":"10.1111/jne.13428","DOIUrl":"10.1111/jne.13428","url":null,"abstract":"<p>Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections were pseudonymised before centralized pathological re-evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re-classification: 30 NEC, 12 NET G3, 3 HG-NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP-NEN, all 17 large-cell NEC (100%), 11/13 (85%) small-cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP-NEN treated with palliative chemotherapy (<i>n</i> = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP-NEN. The NETest was almost always elevated in GEP-NEC and in all large-cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raghava Kashyap, Senthil Raja, Ajay Adusumilli, Murali Mohan Reddy Gopireddy, Benjamin P T Loveday, Ramin Alipour, Grace Kong
Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included 177Lu (n = 142) and 90Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.
{"title":"Role of neoadjuvant peptide receptor radionuclide therapy in unresectable and metastatic gastro-entero-pancreatic neuroendocrine neoplasms: A scoping review.","authors":"Raghava Kashyap, Senthil Raja, Ajay Adusumilli, Murali Mohan Reddy Gopireddy, Benjamin P T Loveday, Ramin Alipour, Grace Kong","doi":"10.1111/jne.13425","DOIUrl":"https://doi.org/10.1111/jne.13425","url":null,"abstract":"<p><p>Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included <sup>177</sup>Lu (n = 142) and <sup>90</sup>Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13425"},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of this study is to conduct a bibliometric analysis of research trends in hyperprolactinemia from 2011 to 2023. This analysis aims to provide researchers with insights into the current hotspots and frontiers related to hyperprolactinemia. It is worth noting that there are currently no existing reports on bibliometric analyses of hyperprolactinemia. The Social Science Citation Index (SSCI) and Science Citation Index Expanded (SCIE) databases of the Web of Science Core Collection were systematically searched for “articles” and “review articles” related to the topic of hyperprolactinemia from 2011 to 2023. VOSviewer was employed to conduct bibliometric analysis, aiming to analyze the research trends in hyperprolactinemia over the past 13 years. A total of 1865 eligible articles were retrieved, with contributions from 9544 scholars representing 83 countries in the field of research. The United States had the highest number of publications, followed by China. The keywords were categorized into six clusters: (1) etiology of hyperprolactinemia and other related endocrine and metabolic diseases. (2) Hyperprolactinemia and mental illness. (3) Diagnosis and management of hyperprolactinemia. (4) Treatment of hyperprolactinemia and prolactinoma. (5) Detection of macroprolactin and macroprolactinemia. (6) Symptoms of male hyperprolactinemia. Over the past 13 years, there has been a consistent and slightly increasing trend in the number of research papers focusing on hyperprolactinemia. The primary areas of research focus are centered around the diagnosis and treatment of hyperprolactinemia caused by antipsychotic drugs or prolactinoma.
{"title":"The research trend of hyperprolactinemia from 2011 to 2023 was analyzed by bibliometrics","authors":"Kaiyan Liu, Jin Zhao, Han Yu, Jing Yang, Yi Ren","doi":"10.1111/jne.13422","DOIUrl":"10.1111/jne.13422","url":null,"abstract":"<p>The objective of this study is to conduct a bibliometric analysis of research trends in hyperprolactinemia from 2011 to 2023. This analysis aims to provide researchers with insights into the current hotspots and frontiers related to hyperprolactinemia. It is worth noting that there are currently no existing reports on bibliometric analyses of hyperprolactinemia. The Social Science Citation Index (SSCI) and Science Citation Index Expanded (SCIE) databases of the Web of Science Core Collection were systematically searched for “articles” and “review articles” related to the topic of hyperprolactinemia from 2011 to 2023. VOSviewer was employed to conduct bibliometric analysis, aiming to analyze the research trends in hyperprolactinemia over the past 13 years. A total of 1865 eligible articles were retrieved, with contributions from 9544 scholars representing 83 countries in the field of research. The United States had the highest number of publications, followed by China. The keywords were categorized into six clusters: (1) etiology of hyperprolactinemia and other related endocrine and metabolic diseases. (2) Hyperprolactinemia and mental illness. (3) Diagnosis and management of hyperprolactinemia. (4) Treatment of hyperprolactinemia and prolactinoma. (5) Detection of macroprolactin and macroprolactinemia. (6) Symptoms of male hyperprolactinemia. Over the past 13 years, there has been a consistent and slightly increasing trend in the number of research papers focusing on hyperprolactinemia. The primary areas of research focus are centered around the diagnosis and treatment of hyperprolactinemia caused by antipsychotic drugs or prolactinoma.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adrian David Marais, Anne Hoffman, Diane Mary Blackhurst, Zephne Margeret van der Spuy
The polycystic ovary syndrome (PCOS) imparts health risks including dyslipidaemia, diabetes and cardiovascular disease that are amenable to lifestyle adjustment and/or medication. We describe dyslipidaemia in women referred to a gynaecological endocrine clinic. Clinical data and endocrine and lipoprotein investigations comprising fasting triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and calculated low density lipoprotein cholesterol (LDLC) were studied along with electrophoresis patterns of apolipoprotein B-containing lipoproteins. The 1721 participants comprised black, mixed ancestry, white and Indian individuals (9.8%, 83.2%, 5.8% and 1.2%, respectively). The mean ± standard deviation of the age, body mass index (BMI) and waist/hip ratio were 26.0 ± 5.9 years, 32.3 ± 8.3 kg/m2 and waist/hip ratio 0.88 ± 0.11, respectively. Overweight status (BMI 26–30 kg/m2) and obesity (BMI >30 kg/m2) involved 272 (15.8%) and 1010 (58.7%) individuals, respectively. Morbid obesity (BMI >40 kg/m2) was present in 309 (17.9%) individuals. The TG, TC, HDLC and LDLC concentrations were 1.22 ± 0.86, 4.77 ± 1.02, 1.3 ± 0.36, 2.94 ± 0.94 mmol/L, respectively. LDL hypercholesterolaemia occurred in 753 (43.7%) and exceeded 5 mmol/L in 39 (2.3%) women. Low HDLC (<0.9 mmol/L) affected 122 (7%), hypertriglyceridaemia (>1.7 mmol/L) affected 265 (15.4%) and exceeded 2.5 mmol/L in 91 (5.3%) women. Mixed hyperlipidaemia (TG >1.7, TC >5.0 mmol/L) occurred in 176 (10.2%). Electrophoresis revealed small LDL particles in 79 (4.6%) and dysbetalipoproteinaemia in 13 (0.76%) of the cohort. Small LDL associated with obesity, blood pressure, TG and glucose concentration and higher androgenic state. Many women with PCOS had unfavourable lipoprotein results: mostly moderate changes in TG, HDLC and LDLC. Small LDL is not rare, may aid risk assessment and is best determined directly. Incidental monogenic disorders of lipoprotein metabolism included dysbetalipoproteinaemia, familial hypercholesterolaemia and severe hypertriglyceridaemia. Dyslipidaemia in PCOS requires more careful diagnosis, individualised management and research.
{"title":"Dyslipidaemia in women with polycystic ovary syndrome referred to a teaching hospital in Cape Town, South Africa","authors":"Adrian David Marais, Anne Hoffman, Diane Mary Blackhurst, Zephne Margeret van der Spuy","doi":"10.1111/jne.13414","DOIUrl":"10.1111/jne.13414","url":null,"abstract":"<p>The polycystic ovary syndrome (PCOS) imparts health risks including dyslipidaemia, diabetes and cardiovascular disease that are amenable to lifestyle adjustment and/or medication. We describe dyslipidaemia in women referred to a gynaecological endocrine clinic. Clinical data and endocrine and lipoprotein investigations comprising fasting triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and calculated low density lipoprotein cholesterol (LDLC) were studied along with electrophoresis patterns of apolipoprotein B-containing lipoproteins. The 1721 participants comprised black, mixed ancestry, white and Indian individuals (9.8%, 83.2%, 5.8% and 1.2%, respectively). The mean ± standard deviation of the age, body mass index (BMI) and waist/hip ratio were 26.0 ± 5.9 years, 32.3 ± 8.3 kg/m<sup>2</sup> and waist/hip ratio 0.88 ± 0.11, respectively. Overweight status (BMI 26–30 kg/m<sup>2</sup>) and obesity (BMI >30 kg/m<sup>2</sup>) involved 272 (15.8%) and 1010 (58.7%) individuals, respectively. Morbid obesity (BMI >40 kg/m<sup>2</sup>) was present in 309 (17.9%) individuals. The TG, TC, HDLC and LDLC concentrations were 1.22 ± 0.86, 4.77 ± 1.02, 1.3 ± 0.36, 2.94 ± 0.94 mmol/L, respectively. LDL hypercholesterolaemia occurred in 753 (43.7%) and exceeded 5 mmol/L in 39 (2.3%) women. Low HDLC (<0.9 mmol/L) affected 122 (7%), hypertriglyceridaemia (>1.7 mmol/L) affected 265 (15.4%) and exceeded 2.5 mmol/L in 91 (5.3%) women. Mixed hyperlipidaemia (TG >1.7, TC >5.0 mmol/L) occurred in 176 (10.2%). Electrophoresis revealed small LDL particles in 79 (4.6%) and dysbetalipoproteinaemia in 13 (0.76%) of the cohort. Small LDL associated with obesity, blood pressure, TG and glucose concentration and higher androgenic state. Many women with PCOS had unfavourable lipoprotein results: mostly moderate changes in TG, HDLC and LDLC. Small LDL is not rare, may aid risk assessment and is best determined directly. Incidental monogenic disorders of lipoprotein metabolism included dysbetalipoproteinaemia, familial hypercholesterolaemia and severe hypertriglyceridaemia. Dyslipidaemia in PCOS requires more careful diagnosis, individualised management and research.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tarryn Radomsky, Ross C. Anderson, Robert P. Millar, Claire L. Newton
G protein-coupled receptors (GPCRs) are central to the functioning of the hypothalamic–pituitary–gonadal axis (HPG axis) and include the rhodopsin-like GPCR family members, neurokinin 3 receptor, kappa-opioid receptor, kisspeptin 1 receptor, gonadotropin-releasing hormone receptor, and the gonadotropin receptors, luteinizing hormone/choriogonadotropin receptor and follicle-stimulating hormone receptor. Unsurprisingly, inactivating variants of these receptors have been implicated in a spectrum of reproductive phenotypes, including failure to undergo puberty, and infertility. Clinical induction of puberty in patients harbouring such variants is possible, but restoration of fertility is not always a realisable outcome, particularly for those patients suffering from primary hypogonadism. Thus, novel pharmaceuticals and/or a fundamental change in approach to treating these patients are required. The increasing wealth of data describing the effects of coding-region genetic variants on GPCR function has highlighted that the majority appear to be dysfunctional as a result of misfolding of the encoded receptor protein, which, in turn, results in impaired receptor trafficking through the secretory pathway to the cell surface. As such, these intracellularly retained receptors may be amenable to ‘rescue’ using a pharmacological chaperone (PC)-based approach. PCs are small, cell permeant molecules hypothesised to interact with misfolded intracellularly retained proteins, stabilising their folding and promoting their trafficking through the secretory pathway. In support of the use of this approach as a viable therapeutic option, it has been observed that many rescued variant GPCRs retain at least a degree of functionality when ‘rescued’ to the cell surface. In this review, we examine the GPCR PC research landscape, focussing on the rescue of inactivating variant GPCRs with important roles in the HPG axis, and describe what is known regarding the mechanisms by which PCs restore trafficking and function. We also discuss some of the merits and obstacles associated with taking this approach forward into a clinical setting.
G 蛋白偶联受体(GPCRs)是下丘脑-垂体-性腺轴(HPG 轴)功能的核心,包括类罗丹明 GPCR 家族成员、神经激肽 3 受体、卡帕类阿片受体、kisspeptin 1 受体、促性腺激素释放激素受体,以及促性腺激素受体、黄体生成素/绒毛促性腺激素受体和卵泡刺激素受体。毫不奇怪,这些受体的失活变体与一系列生殖表型有关,包括无法进入青春期和不育症。临床上可以诱导携带此类变异体的患者进入青春期,但恢复生育能力并非总能实现,尤其是对那些患有原发性性腺功能减退症的患者而言。因此,需要新型药物和/或从根本上改变治疗这些患者的方法。描述编码区基因变异对 GPCR 功能影响的数据越来越丰富,这些数据突出表明,大多数基因变异似乎是由于编码的受体蛋白折叠错误而导致功能障碍,这反过来又会导致受体通过分泌途径向细胞表面的转运功能受损。因此,这些滞留在细胞内的受体可能可以通过基于药理学伴侣(PC)的方法进行 "拯救"。PC 是一种具有细胞渗透性的小分子,据推测能与折叠错误的细胞内滞留蛋白相互作用,稳定它们的折叠并促进它们通过分泌途径进行运输。为了支持将这种方法作为一种可行的治疗方案,我们观察到许多被拯救的变体 GPCR 在被 "拯救 "到细胞表面时至少保留了一定程度的功能。在本综述中,我们审视了 GPCR PC 的研究现状,重点关注在 HPG 轴中发挥重要作用的失活变异 GPCR 的拯救,并介绍了 PC 恢复贩运和功能的已知机制。我们还讨论了将这种方法应用于临床的一些优点和障碍。
{"title":"Restoring function to inactivating G protein-coupled receptor variants in the hypothalamic–pituitary–gonadal axis†","authors":"Tarryn Radomsky, Ross C. Anderson, Robert P. Millar, Claire L. Newton","doi":"10.1111/jne.13418","DOIUrl":"10.1111/jne.13418","url":null,"abstract":"<p>G protein-coupled receptors (GPCRs) are central to the functioning of the hypothalamic–pituitary–gonadal axis (HPG axis) and include the rhodopsin-like GPCR family members, neurokinin 3 receptor, kappa-opioid receptor, kisspeptin 1 receptor, gonadotropin-releasing hormone receptor, and the gonadotropin receptors, luteinizing hormone/choriogonadotropin receptor and follicle-stimulating hormone receptor. Unsurprisingly, inactivating variants of these receptors have been implicated in a spectrum of reproductive phenotypes, including failure to undergo puberty, and infertility. Clinical induction of puberty in patients harbouring such variants is possible, but restoration of fertility is not always a realisable outcome, particularly for those patients suffering from primary hypogonadism. Thus, novel pharmaceuticals and/or a fundamental change in approach to treating these patients are required. The increasing wealth of data describing the effects of coding-region genetic variants on GPCR function has highlighted that the majority appear to be dysfunctional as a result of misfolding of the encoded receptor protein, which, in turn, results in impaired receptor trafficking through the secretory pathway to the cell surface. As such, these intracellularly retained receptors may be amenable to ‘rescue’ using a pharmacological chaperone (PC)-based approach. PCs are small, cell permeant molecules hypothesised to interact with misfolded intracellularly retained proteins, stabilising their folding and promoting their trafficking through the secretory pathway. In support of the use of this approach as a viable therapeutic option, it has been observed that many rescued variant GPCRs retain at least a degree of functionality when ‘rescued’ to the cell surface. In this review, we examine the GPCR PC research landscape, focussing on the rescue of inactivating variant GPCRs with important roles in the HPG axis, and describe what is known regarding the mechanisms by which PCs restore trafficking and function. We also discuss some of the merits and obstacles associated with taking this approach forward into a clinical setting.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannes Leupe, Elin Pauwels, Timon Vandamme, Bliede Van den Broeck, Willem Lybaert, Jeroen Dekervel, Filip Van Herpe, Joris Jaekers, Frederik Cleeren, Johannes Hofland, Adrienne Brouwers, Michel Koole, Guy Bormans, Eric Van Cutsem, Karen Geboes, Annouschka Laenen, Chris Verslype, Sigrid Stroobants, Christophe M. Deroose
[18F]AlF-NOTA-octreotide ([18F]AlF-OC) is a promising alternative for [68Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [18F]AlF-OC PET/CT and [68Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [18F]AlF-OC and [68Ga]Ga-DOTA-TATE or [68Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al., J Nucl Med.2023;63:632–638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [68Ga]Ga-DOTA-SSA or [18F]AlF-OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [18F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [68Ga]Ga-DOTA-SSA, the use of [18F]AlF-OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [18F]AlF-OC. The use of [18F]AlF-OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [18F]AlF-OC PET/CT as an alternative for [68Ga]Ga-DOTA-SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020–000549-15.
{"title":"Clinical impact of using [18F]AlF-NOTA-octreotide PET/CT instead of [68Ga]Ga-DOTA-SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial","authors":"Hannes Leupe, Elin Pauwels, Timon Vandamme, Bliede Van den Broeck, Willem Lybaert, Jeroen Dekervel, Filip Van Herpe, Joris Jaekers, Frederik Cleeren, Johannes Hofland, Adrienne Brouwers, Michel Koole, Guy Bormans, Eric Van Cutsem, Karen Geboes, Annouschka Laenen, Chris Verslype, Sigrid Stroobants, Christophe M. Deroose","doi":"10.1111/jne.13420","DOIUrl":"10.1111/jne.13420","url":null,"abstract":"<p>[<sup>18</sup>F]AlF-NOTA-octreotide ([<sup>18</sup>F]AlF-OC) is a promising alternative for [<sup>68</sup>Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [<sup>18</sup>F]AlF-OC PET/CT and [<sup>68</sup>Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [<sup>18</sup>F]AlF-OC and [<sup>68</sup>Ga]Ga-DOTA-TATE or [<sup>68</sup>Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al., <i>J Nucl Med</i>.2023;63:632–638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [<sup>68</sup>Ga]Ga-DOTA-SSA or [<sup>18</sup>F]AlF-OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [<sup>18</sup>F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [<sup>68</sup>Ga]Ga-DOTA-SSA, the use of [<sup>18</sup>F]AlF-OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [<sup>18</sup>F]AlF-OC. The use of [<sup>18</sup>F]AlF-OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [<sup>18</sup>F]AlF-OC PET/CT as an alternative for [<sup>68</sup>Ga]Ga-DOTA-SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020–000549-15.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Vieyra, Roberto Calderón, Rosa Linares, Gabriela Rosas, Deyra A. Ramírez, Julieta A. Espinoza, Andrea Chaparro, Carlos-Camilo Silva, Roberto Domínguez, Leticia Morales-Ledesma
Reproduction in all mammalian species depends on the growth and maturation of ovarian follicles, that is, folliculogenesis. Follicular development can culminate with the rupture of mature follicles and the consequent expulsion of their oocytes (ovulation) or in atresia, characterized by the arrest of development and eventual degeneration. These processes are regulated by different neuroendocrine signals arising at different hypothalamic nuclei, including the suprachiasmatic nucleus (SCN). In the later, the activation of muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs) by acetylcholine is essential for the regulation of the pre-ovulatory signals that stimulate the rupture of mature follicles. To evaluate the participation of the nAChRs in the SCN throughout the oestrous cycle in the regulation of the hypothalamic–pituitary–ovarian axis. For this purpose, 90-day-old adult female rats in metoestrus, dioestrus, proestrus or oestrus were microinjected into the left- or right-SCN with 0.3 μL of saline solution as vehicle or with 0.225 μg of mecamylamine (Mec), a non-selective antagonist of the nicotinic receptors, diluted in 0.3 μL of vehicle. The animals were sacrificed when they presented vaginal cornification, indicative of oestrus stage, and the effects of the unilateral pharmacological blockade of the nAChRs in the SCN on follicular development, ovulation and secretion of oestradiol and follicle-stimulating hormone (FSH) were evaluated. The microinjection of Mec decreased the serum levels of FSH, which resulted in a lower number of growing and healthy follicles and an increase in atresia. The higher percentage of atresia in pre-ovulatory follicles was related to a decrease in the number of ova shed and abnormalities in oestradiol secretion. We also detected asymmetric responses between the left and right treatments that depended on the stage of the oestrous cycle. The present results allow us to suggest that during all the stages of the oestrous cycle, cholinergic signals that act on the nAChRs in the SCN are pivotal to modulate the secretion of gonadotropins and hence the physiology of the ovaries. Further research is needed to determine if such signals are generated by the cholinergic neurons in the SCN or by cholinergic afferents to the SCN.
{"title":"Pharmacologic blockade of nicotinic receptors in the suprachiasmatic nucleus increases ovarian atresia and inhibits follicular growth","authors":"Elizabeth Vieyra, Roberto Calderón, Rosa Linares, Gabriela Rosas, Deyra A. Ramírez, Julieta A. Espinoza, Andrea Chaparro, Carlos-Camilo Silva, Roberto Domínguez, Leticia Morales-Ledesma","doi":"10.1111/jne.13421","DOIUrl":"10.1111/jne.13421","url":null,"abstract":"<p>Reproduction in all mammalian species depends on the growth and maturation of ovarian follicles, that is, folliculogenesis. Follicular development can culminate with the rupture of mature follicles and the consequent expulsion of their oocytes (ovulation) or in atresia, characterized by the arrest of development and eventual degeneration. These processes are regulated by different neuroendocrine signals arising at different hypothalamic nuclei, including the suprachiasmatic nucleus (SCN). In the later, the activation of muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs) by acetylcholine is essential for the regulation of the pre-ovulatory signals that stimulate the rupture of mature follicles. To evaluate the participation of the nAChRs in the SCN throughout the oestrous cycle in the regulation of the hypothalamic–pituitary–ovarian axis. For this purpose, 90-day-old adult female rats in metoestrus, dioestrus, proestrus or oestrus were microinjected into the left- or right-SCN with 0.3 μL of saline solution as vehicle or with 0.225 μg of mecamylamine (Mec), a non-selective antagonist of the nicotinic receptors, diluted in 0.3 μL of vehicle. The animals were sacrificed when they presented vaginal cornification, indicative of oestrus stage, and the effects of the unilateral pharmacological blockade of the nAChRs in the SCN on follicular development, ovulation and secretion of oestradiol and follicle-stimulating hormone (FSH) were evaluated. The microinjection of Mec decreased the serum levels of FSH, which resulted in a lower number of growing and healthy follicles and an increase in atresia. The higher percentage of atresia in pre-ovulatory follicles was related to a decrease in the number of ova shed and abnormalities in oestradiol secretion. We also detected asymmetric responses between the left and right treatments that depended on the stage of the oestrous cycle. The present results allow us to suggest that during all the stages of the oestrous cycle, cholinergic signals that act on the nAChRs in the SCN are pivotal to modulate the secretion of gonadotropins and hence the physiology of the ovaries. Further research is needed to determine if such signals are generated by the cholinergic neurons in the SCN or by cholinergic afferents to the SCN.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infections during pregnancy are associated with increased risk for adult neuropsychiatric disease, such as major depressive disorder, schizophrenia, and autism spectrum disorder. In mouse models of maternal immune activation (MIA), different toll-like receptors (TLRs) are stimulated to initiate inflammatory responses in mother and fetus. The goal of this study was to determine sex-dependent aspects of MIA using a TLR7/8 agonist, Resiquimod (RQ), on neurodevelopment. RQ was administered to timed-pregnant mice on embryonic day (E) 12.5. At E15, maternal/fetal plasma cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Maternal cytokines interleukin (IL)-6 and IL-10 were higher while tumor necrosis factor (TNF)-α and IL-17 were lower in pregnant dams exposed to RQ. Fetal cytokines (E15) were altered at the same timepoint with fetal plasma IL-6 and IL-17 greater after RQ compared to vehicle, while IL-10 and TNF-α were higher in male fetuses but not female. Other timed-pregnant dams were allowed to give birth. MIA with RQ did not alter the female to male ratio of offspring born per litter. Body weights were reduced significantly in both sexes at birth, and over the next 5 weeks. Offspring from RQ-injected mothers opened their eyes 5 days later than controls. Similarly, female offspring from RQ-injected mothers exhibited pubertal delay based on vaginal opening 2–3 days later than control females. On the behavioral side, juvenile and adult male and female MIA offspring exhibited less social-like behavior in a social interaction test. Anhedonia-like behavior was greater in MIA adult female mice. This study provides support for sex-dependent influences of fetal antecedents for altered brain development and behavioral outputs that could be indicative of increased susceptibility for adult disorders through immune mechanisms. Future studies are needed to determine neural cellular and molecular mechanisms for such programming effects.
{"title":"Maternal immune activation with toll-like receptor 7 agonist during mid-gestation alters juvenile and adult developmental milestones and behavior","authors":"Julietta A. Sheng, Stuart A. Tobet","doi":"10.1111/jne.13417","DOIUrl":"10.1111/jne.13417","url":null,"abstract":"<p>Infections during pregnancy are associated with increased risk for adult neuropsychiatric disease, such as major depressive disorder, schizophrenia, and autism spectrum disorder. In mouse models of maternal immune activation (MIA), different toll-like receptors (TLRs) are stimulated to initiate inflammatory responses in mother and fetus. The goal of this study was to determine sex-dependent aspects of MIA using a TLR7/8 agonist, Resiquimod (RQ), on neurodevelopment. RQ was administered to timed-pregnant mice on embryonic day (E) 12.5. At E15, maternal/fetal plasma cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Maternal cytokines interleukin (IL)-6 and IL-10 were higher while tumor necrosis factor (TNF)-α and IL-17 were lower in pregnant dams exposed to RQ. Fetal cytokines (E15) were altered at the same timepoint with fetal plasma IL-6 and IL-17 greater after RQ compared to vehicle, while IL-10 and TNF-α were higher in male fetuses but not female. Other timed-pregnant dams were allowed to give birth. MIA with RQ did not alter the female to male ratio of offspring born per litter. Body weights were reduced significantly in both sexes at birth, and over the next 5 weeks. Offspring from RQ-injected mothers opened their eyes 5 days later than controls. Similarly, female offspring from RQ-injected mothers exhibited pubertal delay based on vaginal opening 2–3 days later than control females. On the behavioral side, juvenile and adult male and female MIA offspring exhibited less social-like behavior in a social interaction test. Anhedonia-like behavior was greater in MIA adult female mice. This study provides support for sex-dependent influences of fetal antecedents for altered brain development and behavioral outputs that could be indicative of increased susceptibility for adult disorders through immune mechanisms. Future studies are needed to determine neural cellular and molecular mechanisms for such programming effects.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sebastien G. Bouret, Hubert Vaudry, Vincent Prevot
<p>Roger Guillemin was born in Dijon, Burgundy (France) on January 11, 1924. In 1942, he began studying Medicine at the University of Burgundy. After a mandatory break during World War I, he obtained his medical degree from the Faculty of Medicine of Lyon in 1949.</p><p>He began to practice as a family doctor, during which he acquired many excellent memories. However, he also quickly realized the limitations of medicine at that time. He recalled that he “could only prescribe three types of medicine, one of which being aspirin.” His scientific curiosity made him read specialized journals, which made him aware of Hans Selye's research in Montreal on the “General Adaptation Syndrome,” now known as the endocrine reaction of the organism to stress. He heard that the Canadian professor was invited to give a series of lectures at the Pitié Hospital and decided to attend his talks. Fortunately, Hans Selye presented his lectures in French, as Roger Guillemin did not speak English at that time. At the end of the third lecture, he introduced himself to Pr. Selye and asked him if he could join his lab for a year to prepare for his medical doctorate. Roger Guillemin left his native Burgundy and flew to Montreal. During his stay in Pr. Selye's laboratory, he first prepared a medical thesis, followed by a PhD in Physiology, specializing in Experimental Endocrinology, which he obtained in 1953.</p><p>Pr. Selye was the head of the Institute of Experimental Medicine and Surgery, where he established a series of lectures called “The Claude Bernard Lectures” inviting internationally renowned researchers. This is how Roger Guillemin met Geoffrey Harris, who is nowadays considered the father of Neuroendocrinology. Through various approaches of electrical stimulation, ligation or section of the pituitary stalk, and pituitary transplantation, Pr. Harris demonstrated a key role of the portal system in the relationship between the hypothalamus and the adenohypophysis.<span><sup>1</sup></span> Harris's work made it possible to understand how the “first mediators” (according to Selye's terminology), which will later be called “releasing factors,” reached the pituitary cells. The objective of Roger Guillemin was now clear: to chemically identify hypothalamic factors that govern the anterior pituitary's function, starting with the neural mediator suspected by Hans Selye controlling the hypothalamic–pituitary–adrenal axis.</p><p>Hans Selye's laboratory did not have the equipment and expertise to identify chemical factors governing the anterior pituitary function. Roger Guillemin decided to move to the Department of Physiology of Baylor College in Houston, Texas, which was headed by Hebbel Hoff. However, Roger Guillemin did not have the expertise to purify the hypothalamic factors he was looking for. Therefore, he teamed up with talented (bio)chemists, including Walter Hearn, with whom he used paper chromatography on a few dozen sheep hypothalami with the hope of isolating the
{"title":"In memoriam: Roger Guillemin, neuroendocrinologist, Nobel Prize in physiology or medicine","authors":"Sebastien G. Bouret, Hubert Vaudry, Vincent Prevot","doi":"10.1111/jne.13419","DOIUrl":"10.1111/jne.13419","url":null,"abstract":"<p>Roger Guillemin was born in Dijon, Burgundy (France) on January 11, 1924. In 1942, he began studying Medicine at the University of Burgundy. After a mandatory break during World War I, he obtained his medical degree from the Faculty of Medicine of Lyon in 1949.</p><p>He began to practice as a family doctor, during which he acquired many excellent memories. However, he also quickly realized the limitations of medicine at that time. He recalled that he “could only prescribe three types of medicine, one of which being aspirin.” His scientific curiosity made him read specialized journals, which made him aware of Hans Selye's research in Montreal on the “General Adaptation Syndrome,” now known as the endocrine reaction of the organism to stress. He heard that the Canadian professor was invited to give a series of lectures at the Pitié Hospital and decided to attend his talks. Fortunately, Hans Selye presented his lectures in French, as Roger Guillemin did not speak English at that time. At the end of the third lecture, he introduced himself to Pr. Selye and asked him if he could join his lab for a year to prepare for his medical doctorate. Roger Guillemin left his native Burgundy and flew to Montreal. During his stay in Pr. Selye's laboratory, he first prepared a medical thesis, followed by a PhD in Physiology, specializing in Experimental Endocrinology, which he obtained in 1953.</p><p>Pr. Selye was the head of the Institute of Experimental Medicine and Surgery, where he established a series of lectures called “The Claude Bernard Lectures” inviting internationally renowned researchers. This is how Roger Guillemin met Geoffrey Harris, who is nowadays considered the father of Neuroendocrinology. Through various approaches of electrical stimulation, ligation or section of the pituitary stalk, and pituitary transplantation, Pr. Harris demonstrated a key role of the portal system in the relationship between the hypothalamus and the adenohypophysis.<span><sup>1</sup></span> Harris's work made it possible to understand how the “first mediators” (according to Selye's terminology), which will later be called “releasing factors,” reached the pituitary cells. The objective of Roger Guillemin was now clear: to chemically identify hypothalamic factors that govern the anterior pituitary's function, starting with the neural mediator suspected by Hans Selye controlling the hypothalamic–pituitary–adrenal axis.</p><p>Hans Selye's laboratory did not have the equipment and expertise to identify chemical factors governing the anterior pituitary function. Roger Guillemin decided to move to the Department of Physiology of Baylor College in Houston, Texas, which was headed by Hebbel Hoff. However, Roger Guillemin did not have the expertise to purify the hypothalamic factors he was looking for. Therefore, he teamed up with talented (bio)chemists, including Walter Hearn, with whom he used paper chromatography on a few dozen sheep hypothalami with the hope of isolating the ","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}