Pub Date : 2024-02-01DOI: 10.1016/j.steroids.2024.109378
Yan Song , Juan Zhao , Dan Liu , Jie Zhang
Background
24-h urinary free cortisol (UFF) is recommended for screening of Cushing's syndrome (CS), a rare disease characterized by apparent cortisol and cortisone excess. We aimed to validate a simple LC-MS/MS method for accurate measurement of UFF and urinary free cortisone (UFE), establishment of reference ranges, and evaluation of performance for CS diagnosis.
Methods
Urine samples were processed using solid-phase extraction cartridges, followed by elution with methanol and acetonitrile. Analysis was performed via tandem mass spectrometry, utilizing multiple reaction monitoring and electrospray ionization source in positive ion mode.
Results
The assay displayed excellent linearity (r > 0.99) in the range of 0.05–100 ng/mL for cortisol and 0.25–500 ng/mL for cortisone, with lower limits of quantification (LLOQ) at 0.05 ng/mL for cortisol and 0.25 ng/mL for cortisone. The obtained results for intra-day and inter-day imprecision for both analytes were within the acceptable range of less than 10 %. The trueness values for both compounds were also within the acceptable limit of 15 %. No significant matrix effects or carry over observed in our method. The reference intervals of UFF, UFE and UFF:UFE ratio were 7.01–45.66 µg/24-h, 27.97–139.21 µg/24-h and 0.17–0.56, respectively. UFF > 56.75 µg/24-h showed 100 % specificity and 100 % sensitivity for CS diagnosis, which was superior to UFF:UFE ratio.
Conclusions
We developed and validated a sensitive LC-MS/MS method to detect UFF and UFE. Our data indicate that UFF measured by the current LC-MS/MS assay exhibited high diagnostic performance for CS.
{"title":"Validation of a LC-MS/MS method for establishing reference intervals and assessing diagnostic performance of urinary free cortisol and cortisone","authors":"Yan Song , Juan Zhao , Dan Liu , Jie Zhang","doi":"10.1016/j.steroids.2024.109378","DOIUrl":"10.1016/j.steroids.2024.109378","url":null,"abstract":"<div><h3>Background</h3><p>24-h urinary free cortisol (UFF) is recommended for screening of Cushing's syndrome (CS), a rare disease characterized by apparent cortisol and cortisone excess. We aimed to validate a simple LC-MS/MS method for accurate measurement of UFF and urinary free cortisone (UFE), establishment of reference ranges, and evaluation of performance for CS diagnosis.</p></div><div><h3>Methods</h3><p>Urine samples were processed using solid-phase extraction cartridges, followed by elution with methanol and acetonitrile. Analysis was performed via tandem mass spectrometry, utilizing multiple reaction monitoring and electrospray ionization source in positive ion mode.</p></div><div><h3>Results</h3><p>The assay displayed excellent linearity (r > 0.99) in the range of 0.05–100 ng/mL for cortisol and 0.25–500 ng/mL for cortisone, with lower limits of quantification (LLOQ) at 0.05 ng/mL for cortisol and 0.25 ng/mL for cortisone. The obtained results for intra-day and inter-day imprecision for both analytes were within the acceptable range of less than 10 %. The trueness values for both compounds were also within the acceptable limit of 15 %. No significant matrix effects or carry over observed in our method. The reference intervals of UFF, UFE and UFF:UFE ratio were 7.01–45.66 µg/24-h, 27.97–139.21 µg/24-h and 0.17–0.56, respectively. UFF > 56.75 µg/24-h showed 100 % specificity and 100 % sensitivity for CS diagnosis, which was superior to UFF:UFE ratio.</p></div><div><h3>Conclusions</h3><p>We developed and validated a sensitive LC-MS/MS method to detect UFF and UFE. Our data indicate that UFF measured by the current LC-MS/MS assay exhibited high diagnostic performance for CS.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681583","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}
Pub Date : 2024-01-28DOI: 10.1016/j.steroids.2024.109379
Liana Zakirova, Irina Baikova, Alexander Lobov, Olga Kukovinets, Oxana Кazakova
A series of 2E-furfurylidene-23-nor- and 24-nor-allobetulins has been synthesized by the Claisen-Schmidt condensation and conditions of their formation were studied in detail. It was found that among an expected 2E-furfurylidene-3-oxo-24-nor-allobetulin 4 two byproducts holding 3-oxo-4α-hydroxy- 5 and 3β,4α-dihydroxy- 6 substituents were formed, which could become the main products under the change of reaction time and amount of the base solution. Moreover, a conversion of individual 2E-furfurylidene-23-nor-3-oxo-4α-hydroxy- 5 into 2E-furfurylidene-23-nor-3β,4α-dihydroxy-derivative 6 under the treatment with the base solution was observed. An inversion of the configuration at C4 from 24-nor- to 23-nor-allobetulins for compounds 5 – 7 was proved by the NMR spectra. The probable explanation of compound 5 formation includes oxidation by atmospheric oxygen to 4-hydroperoxide, which was further transformed into 4-hydroxy-group. In the presence of the base the reduction C3(=O)-function of compound 5 occurs like Meerwein– Ponndorf–Verley reaction to give compound 6. As a result, a difference in the reactivity of native allobetulin scaffold and 24-nor-allobetulin in the Claisen-Schmidt condensation was observed and a first case of conversion 24-nor- to 23-nor-allobetulin derivatives was described.
{"title":"An unexpected conversion of 2E-furfurylidene-3-oxo-24-nor-allobetulin to 23-nor-allobetulins","authors":"Liana Zakirova, Irina Baikova, Alexander Lobov, Olga Kukovinets, Oxana Кazakova","doi":"10.1016/j.steroids.2024.109379","DOIUrl":"10.1016/j.steroids.2024.109379","url":null,"abstract":"<div><p>A series of 2<em>E</em>-furfurylidene-23-nor- and 24-nor-allobetulins has been synthesized by the Claisen-Schmidt condensation and conditions of their formation were studied in detail. It was found that among an expected 2<em>E</em>-furfurylidene-3-oxo-24-nor-allobetulin <strong>4</strong> two byproducts holding 3-oxo-4<em>α</em>-hydroxy- <strong>5</strong> and 3<em>β</em>,4<em>α</em>-dihydroxy- <strong>6</strong> substituents were formed, which could become the main products under the change of reaction time and amount of the base solution. Moreover, a conversion of individual 2<em>E</em>-furfurylidene-23-nor-3-oxo-4<em>α</em>-hydroxy- <strong>5</strong> into 2<em>E</em>-furfurylidene-23-nor-3<em>β</em>,4<em>α</em>-dihydroxy-derivative <strong>6</strong> under the treatment with the base solution was observed. An inversion of the configuration at C4 from 24-nor- to 23-nor-allobetulins for compounds <strong>5</strong> – <strong>7</strong> was proved by the NMR spectra. The probable explanation of compound <strong>5</strong><span> formation includes oxidation by atmospheric oxygen to 4-hydroperoxide, which was further transformed into 4-hydroxy-group. In the presence of the base the reduction C3(=O)-function of compound </span><strong>5</strong> occurs like Meerwein– Ponndorf–Verley reaction to give compound <strong>6</strong>. As a result, a difference in the reactivity of native allobetulin scaffold and 24-nor-allobetulin in the Claisen-Schmidt condensation was observed and a first case of conversion 24-nor- to 23-nor-allobetulin derivatives was described.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575488","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}
Pub Date : 2024-01-24DOI: 10.1016/j.steroids.2024.109368
Soledad Henríquez , Maria Jose Valdivia , Monica Mainigi , Claudio Villarroel , Luis Velasquez , Jerome F. Strauss III , Luigi Devoto
Estrogens produced by the ovary play diverse roles in controlling physiological changes in the function of the female reproductive system. Although estradiol acts through classical nuclear receptors, its metabolites (EMs) act by alternative pathways. It has been postulated that EMs act through paracrine-autocrine pathways to regulate key processes involved in normal follicular growth, corpus luteum (CL) development, function, and regression. The present review describes recent advances in understanding the role of EMs in human ovarian physiology during the menstrual cycle, including their role in anovulatory disorders and their action in other target tissues.
{"title":"The role of estrogen metabolites in human ovarian function","authors":"Soledad Henríquez , Maria Jose Valdivia , Monica Mainigi , Claudio Villarroel , Luis Velasquez , Jerome F. Strauss III , Luigi Devoto","doi":"10.1016/j.steroids.2024.109368","DOIUrl":"10.1016/j.steroids.2024.109368","url":null,"abstract":"<div><p>Estrogens produced by the ovary play diverse roles in controlling physiological changes in the function of the female reproductive system. Although estradiol acts through classical nuclear receptors, its metabolites (EMs) act by alternative pathways. It has been postulated that EMs act through paracrine-autocrine pathways to regulate key processes involved in normal follicular growth, corpus luteum (CL) development, function, and regression. The present review describes recent advances in understanding the role of EMs in human ovarian physiology during the menstrual cycle, including their role in anovulatory disorders and their action in other target tissues.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567527","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}
Pub Date : 2024-01-24DOI: 10.1016/j.steroids.2023.109362
Paul B. Reese
Research published between 2001 and 2022 on the functionalization of remote positions of steroids, as well as the use of this technique in the generation of biologically active compounds has been reviewed. In the first section of the analysis established and novel methods for activation of sites deemed to be remote were reported. A series of manganese- (mainly), rhodium-, ruthenium- and osmium-centered porphyrins as catalysts in the presence of PIDA as oxidant have effected hydroxylation at C-1, -5, -6, -7, -11, -14, -15, -16, -17, -20, -24 and -25. Dioxiranes have been utilized in inserting hydroxyl groups at the 5, 12, 14, 15, 16, 17, 20, 24 and 25 positions (tertiary centers for the most part). Alcohols at C-12 and -16 were oxidized further to ketones. The Schönecker oxidation, discovered and developed during the period, has revolutionized the selective functionalization at C-12 of steroids possessing a 17-keto group. In the presence of iron-centered PDP- and MCP-based catalysts, hydrogen peroxide and acetic acid, substrates tended to be hydroxylated at C-6 and -12, with further oxidation to ketones often accompanying this reaction. The hypohalite reaction, utilizing the more modern Suarez conditions (irradiation in the presence of iodine and PIDA), was reported to facilitate the insertion of a hydroxyl moiety five atoms away from an existing alcohol oxygen. Steroidal-3β-diazoacetates tend to decompose on heating with di-rhodium-centered catalysts while activating carbons four or five atoms away. Chromium- and iron-based acetates were observed to functionalize C-5 and -25. Other reactions involving ring cleavage and halogenation, ketone irradiation and α-hydroxylation of ethers were also covered.
The syntheses of compounds with marked biological activity from readily available steroids is described in the second section of the study. Cyclopamine, cephalostatin-1, ritterazine B and three polyhydroxypregnanaes (pergularin, utendin and tomentogenin) were generated in sequences in which a key step required hydroxylation at C-12 using the Schönecker reaction. A crucial stage in the preparation of cortistatin A, the saundersioside core, eurysterol A, 5,6-dihydroglaucogenin C, as well as clinostatins A and B involved the functionalization of C-18 or -19 utilizing hypohalite chemistry. The synthetic route to xestobergsterol A, pavonin-4-aglycone and ouagabagenin included a transformation where ketone irradiation played a part in either producing a Δ14 or a C-19 activated steroid. The radical relay reaction, where a 17α-chloro-steroid was formed, was central in the generation of pythocholic acid. The lead tetraacetate reaction was pivotal in the functionalization of C-19 during the synthesis of cyclocitrinol.
{"title":"Remote functionalization reactions in steroids: discovery and application","authors":"Paul B. Reese","doi":"10.1016/j.steroids.2023.109362","DOIUrl":"10.1016/j.steroids.2023.109362","url":null,"abstract":"<div><p>Research published between 2001 and 2022 on the functionalization of remote positions of steroids, as well as the use of this technique in the generation of biologically active compounds has been reviewed. In the first section of the analysis established and novel methods for activation of sites deemed to be remote were reported. A series of manganese- (mainly), rhodium-, ruthenium- and osmium-centered porphyrins as catalysts in the presence of PIDA as oxidant have effected hydroxylation at C-1, -5, -6, -7, -11, -14, -15, -16, -17, -20, -24 and -25. Dioxiranes have been utilized in inserting hydroxyl groups at the 5, 12, 14, 15, 16, 17, 20, 24 and 25 positions (tertiary centers for the most part). Alcohols at C-12 and -16 were oxidized further to ketones. The Schönecker oxidation, discovered and developed during the period, has revolutionized the selective functionalization at C-12 of steroids possessing a 17-keto group. In the presence of iron-centered PDP- and MCP-based catalysts, hydrogen peroxide and acetic acid, substrates tended to be hydroxylated at C-6 and -12, with further oxidation to ketones often accompanying this reaction. The hypohalite reaction, utilizing the more modern Suarez conditions (irradiation in the presence of iodine and PIDA), was reported to facilitate the insertion of a hydroxyl moiety five atoms away from an existing alcohol oxygen. Steroidal-3β-diazoacetates tend to decompose on heating with di-rhodium-centered catalysts while activating carbons four or five atoms away. Chromium- and iron-based acetates were observed to functionalize C-5 and -25. Other reactions involving ring cleavage and halogenation, ketone irradiation and α-hydroxylation of ethers were also covered.</p><p>The syntheses of compounds with marked biological activity from readily available steroids is described in the second section of the study. Cyclopamine, cephalostatin-1, ritterazine B and three polyhydroxypregnanaes (pergularin, utendin and tomentogenin) were generated in sequences in which a key step required hydroxylation at C-12 using the Schönecker reaction. A crucial stage in the preparation of cortistatin A, the saundersioside core, eurysterol A, 5,6-dihydroglaucogenin C, as well as clinostatins A and B involved the functionalization of C-18 or -19 utilizing hypohalite chemistry. The synthetic route to xestobergsterol A, pavonin-4-aglycone and ouagabagenin included a transformation where ketone irradiation played a part in either producing a Δ<sup>14</sup> or a C-19 activated steroid. The radical relay reaction, where a 17α-chloro-steroid was formed, was central in the generation of pythocholic acid. The lead tetraacetate reaction was pivotal in the functionalization of C-19 during the synthesis of cyclocitrinol.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567524","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}
While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.
虽然孕酮对绝经前体重和食欲的影响已得到充分阐明,但其对绝经后体重和食欲的影响尚未明确。相反,雌激素对绝经后体重和食欲的影响已得到充分证实。本研究评估了黄体酮治疗对卵巢切除大鼠体重、食欲和脂肪量的影响。此外,还检测了催产素(OT)、瘦素及其受体(这些都是有效的厌食因子)的中枢和/或外周水平。雌性大鼠卵巢切除后分为对照组、黄体酮处理组和雌激素处理组。黄体酮组和雌激素组的体重、进食量和皮下脂肪量均低于对照组。雌激素组的血清 OT 水平高于对照组,而黄体酮组和对照组的 OT 水平没有差异。黄体酮组和雌激素组的血清瘦素水平均低于对照组。对下丘脑和脂肪组织中的 OT、瘦素及其受体进行基因表达分析后发现,各组之间几乎没有显著差异。黄体酮组和雌激素组参与食欲调节的下丘脑神经肽Y(NPY)和前泌乳素皮质素(POMC)mRNA水平略有变化。这些研究结果表明,黄体酮治疗可能会对绝经后的体重、食欲和脂肪量调节产生有利影响,而且黄体酮产生这些影响的机制与雌激素产生这些影响的机制不同。
{"title":"Progesterone treatment reduces food intake and body weight in ovariectomized female rats","authors":"Maimi Uchishiba , Shota Yamamoto , Asuka Takeda , Ryosuke Arakaki , Moeka Arata , Hiroki Noguchi , Hidenori Aoki , Kou Tamura , Takaaki Maeda , Saki Minato , Mari Nii , Hiroaki Inui , Shuhei Kamada , Riyo Kinouchi , Yuri Yamamoto , Kanako Yoshida , Shigetaka Yagi , Takeshi Kato , Takashi Kaji , Masato Nishimura , Takeshi Iwasa","doi":"10.1016/j.steroids.2024.109367","DOIUrl":"10.1016/j.steroids.2024.109367","url":null,"abstract":"<div><p>While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547144","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}
Pub Date : 2024-01-18DOI: 10.1016/j.steroids.2024.109366
Mariele Ilario Zucão , Vitor Grigio , Luiz Henrique Alves Guerra , Julia Quilles Antoniassi , Nayara Fernanda da Costa Castro , Sebastião Roberto Taboga , Patricia Simone Leite Vilamaior
The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate’s adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging.
{"title":"Aging effects in adrenal cortex of male Mongolian gerbil: A model for endocrine studies","authors":"Mariele Ilario Zucão , Vitor Grigio , Luiz Henrique Alves Guerra , Julia Quilles Antoniassi , Nayara Fernanda da Costa Castro , Sebastião Roberto Taboga , Patricia Simone Leite Vilamaior","doi":"10.1016/j.steroids.2024.109366","DOIUrl":"10.1016/j.steroids.2024.109366","url":null,"abstract":"<div><p>The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate’s adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males <em>Meriones unguiculatus</em>, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502192","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}
Pub Date : 2024-01-04DOI: 10.1016/j.steroids.2024.109363
Alejandra Monserrat Retis-Resendiz , Yesenia Cid-Cruz , Dora María Velázquez-Hernández , Jessica Romero-Reyes , Moisés León-Juárez , Elizabeth García-Gómez , Ignacio Camacho-Arroyo , Edgar Ricardo Vázquez-Martínez
Decidualization, a crucial process for successful pregnancy establishment and maintenance, involves endometrial stromal cell differentiation. This process is orchestrated by estradiol (E2), progesterone, and other stimuli that increase intracellular cyclic adenosine monophosphate (cAMP) levels. The intracellular progesterone receptor (PR), encoded by the PGR gene, has a key role in decidualization.
This study aimed to understand the role of sex steroids and cAMP in regulating PGR expression during the in vitro decidualization of the human immortalized endometrial stromal cell line, T-HESC. We subjected the cells to individual and combined treatments of E2, medroxyprogesterone (MPA), and cAMP. Additionally, we treated cells with PR and estrogen receptor antagonists and a protein kinase A (PKA) inhibitor. We evaluated the expression of PGR isoforms and decidualization-associated genes by RT-qPCR.
Our findings revealed that cAMP induced PGR-B and PGR-AB expression by activating the PKA signaling pathway, while MPA downregulated their expression through the PR. Furthermore, downstream genes involved in decidualization, such as those coding for prolactin (PRL), insulin-like growth factor-binding protein-1 (IGFBP1), and Dickkopf-1 (DKK1), exhibited positive regulation via the cAMP-PKA pathway. Remarkably, MPA-activated PR signaling induced the expression of IGFBP1 and DKK1 but inhibited that of PRL.
In conclusion, we have demonstrated that the PKA signaling pathway induces PGR gene expression during in vitro decidualization of the T-HESC human endometrial stromal cell line. This study has unraveled some of the intricate regulatory mechanisms governing PGR expression during this fundamental process for implantation and pregnancy maintenance.
{"title":"cAMP regulates the progesterone receptor gene expression through the protein kinase A pathway during decidualization in human immortalized endometrial stromal cells","authors":"Alejandra Monserrat Retis-Resendiz , Yesenia Cid-Cruz , Dora María Velázquez-Hernández , Jessica Romero-Reyes , Moisés León-Juárez , Elizabeth García-Gómez , Ignacio Camacho-Arroyo , Edgar Ricardo Vázquez-Martínez","doi":"10.1016/j.steroids.2024.109363","DOIUrl":"10.1016/j.steroids.2024.109363","url":null,"abstract":"<div><p>Decidualization, a crucial process for successful pregnancy establishment and maintenance, involves endometrial stromal cell differentiation. This process is orchestrated by estradiol (E2), progesterone, and other stimuli that increase intracellular cyclic adenosine monophosphate (cAMP) levels. The intracellular progesterone receptor (PR), encoded by the <em>PGR</em> gene, has a key role in decidualization.</p><p>This study aimed to understand the role of sex steroids and cAMP in regulating <em>PGR</em> expression during the <em>in vitro</em> decidualization of the human immortalized endometrial stromal cell line, <em>T</em>-HESC. We subjected the cells to individual and combined treatments of E2, medroxyprogesterone (MPA), and cAMP. Additionally, we treated cells with PR and estrogen receptor antagonists and a protein kinase A (PKA) inhibitor. We evaluated the expression of <em>PGR</em> isoforms and decidualization-associated genes by RT-qPCR.</p><p>Our findings revealed that cAMP induced <em>PGR-B</em> and <em>PGR-AB</em> expression by activating the PKA signaling pathway, while MPA downregulated their expression through the PR. Furthermore, downstream genes involved in decidualization, such as those coding for prolactin (<em>PRL)</em>, insulin-like growth factor-binding protein-1 (<em>IGFBP1</em>), and Dickkopf-1 (<em>DKK1</em>), exhibited positive regulation via the cAMP-PKA pathway. Remarkably, MPA-activated PR signaling induced the expression of <em>IGFBP1</em> and <em>DKK1</em> but inhibited that of <em>PRL</em>.</p><p>In conclusion, we have demonstrated that the PKA signaling pathway induces <em>PGR</em> gene expression during <em>in vitro</em> decidualization of the <em>T</em>-HESC human endometrial stromal cell line. This study has unraveled some of the intricate regulatory mechanisms governing <em>PGR</em> expression during this fundamental process for implantation and pregnancy maintenance.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106667","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}
In the wake of the Novel Coronavirus arrival, the world witnessed the fragility of healthcare systems and the resilience of healthcare workers who stood on the front lines. SARS-CoV-2, also known as COVID-19 or severe acute respiratory syndrome, first appeared in China in December 2019. The infection quickly spread across the nation and the world. All countries severely restricted social interaction to stop the virus's transmission, impacting all sporting, social, and recreational activities. Anabolic androgenic steroids (AASs) are frequently used illegally to enhance strength and physical attractiveness. However, they could hurt immune system health. Much research hasn't been done yet on the connection between Covid-19 and AASs. Synthetic testosterone analogs known as anabolic androgenic steroids (AASs) can have an immune-system-altering effect. Sportspeople and bodybuilders are vulnerable to AAS abuse. Governmental reactions to the coronavirus infection issue over the last year have drawn much attention and discussion regarding public services, the experience and lessons learned from different limitations, and strategies for dealing with potential future pandemics. Using AAS has the potential to cause a variety of adverse reactions, including cardiovascular issues (including high blood pressure, heart disease, and blood clots), liver damage, renal failure, mood swings, aggressiveness, and psychiatric disorders. Individuals already suffering from severe respiratory conditions like COVID-19 may have these risks increased. This review mainly highlights the anabolic androgen steroids use and its unseen effects on coronavirus patients and gymnastics.
{"title":"Impact of anabolic androgenic steroids on COVID-19","authors":"Khaja Moinuddin shaik, Vijay Patibandla, Sukhendu Nandi","doi":"10.1016/j.steroids.2023.109361","DOIUrl":"10.1016/j.steroids.2023.109361","url":null,"abstract":"<div><p>In the wake of the Novel Coronavirus arrival, the world witnessed the fragility of healthcare systems and the resilience of healthcare workers who stood on the front lines. SARS-CoV-2, also known as COVID-19 or severe acute respiratory syndrome, first appeared in China in December 2019. The infection quickly spread across the nation and the world. All countries severely restricted social interaction to stop the virus's transmission, impacting all sporting, social, and recreational activities. Anabolic androgenic steroids (AASs) are frequently used illegally to enhance strength and physical attractiveness. However, they could hurt immune system health. Much research hasn't been done yet on the connection between Covid-19 and AASs. Synthetic testosterone analogs known as anabolic androgenic steroids (AASs) can have an immune-system-altering effect. Sportspeople and bodybuilders are vulnerable to AAS abuse. Governmental reactions to the coronavirus infection issue over the last year have drawn much attention and discussion regarding public services, the experience and lessons learned from different limitations, and strategies for dealing with potential future pandemics. Using AAS has the potential to cause a variety of adverse reactions, including cardiovascular issues (including high blood pressure, heart disease, and blood clots), liver damage, renal failure, mood swings, aggressiveness, and psychiatric disorders. Individuals already suffering from severe respiratory conditions like COVID-19 may have these risks increased. This review mainly highlights the anabolic androgen steroids use and its unseen effects on coronavirus patients and gymnastics.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098728","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}
Pub Date : 2023-12-21DOI: 10.1016/j.steroids.2023.109353
Yves Jacquot, Patricia de Cremoux, Brian J. Harvey, Martin Wehling
{"title":"Editorial: 13th International Meeting on Rapid Responses to Steroid Hormones, Paris, 20–23 September 2022 - In Memoriam Anthony W. Norman (1938–2019)","authors":"Yves Jacquot, Patricia de Cremoux, Brian J. Harvey, Martin Wehling","doi":"10.1016/j.steroids.2023.109353","DOIUrl":"10.1016/j.steroids.2023.109353","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138886059","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}
Pub Date : 2023-12-20DOI: 10.1016/j.steroids.2023.109352
Aline da Silva Pereira , Nathieli Bianchin Bottari, Jelson Norberto Nauderer, Charles Elias Assmann, Priscila Marquezan Copetti, Karine Paula Reichert, Vitor Bastianello Mostardeiro, Marcylene Vieira da Silveira, Vera Maria Melchiors Morsch, Maria Rosa Chitolina Schetinger
Physical exercise is recognized as a non-pharmacological approach to treat and protect against several neuroinflammatory conditions and thus to prevent brain disorders. However, the interest in ergogenic resources by athletes and bodybuilding practitioners is widespread and on the rise. These substances shorten the process of performance gain and improve aesthetics, having led to the prominent use and abuse of hormones in the past years. Recent evidence has shown that the purinergic system, composed of adenine nucleotides, nucleosides, enzymes, and receptors, participates in a wide range of processes within the brain, such as neuroinflammation, neuromodulation, and cellular communication. Here, we investigated the effects of the anabolic androgenic steroid (AAS) testosterone (TES) at a dose of 70 mg/kg/week in female rats and the neuroprotective effect of resistance exercise related to the purinergic system and oxidative stress parameters. Our findings showed a decrease in ATP and ADO hydrolysis in treated and trained animals. Furthermore, there was an increase in the density of purinoceptors (P2X7 and A2A) and inflammatory markers (IBA-1, NRLP3, CASP-1, IL-1β, and IL-6) in the cerebral cortex of animals that received AAS. On the other hand, exercise reversed neuroinflammatory parameters such as IBA-1, NLRP3, CASP-1, and IL-1β and improved antioxidant response and anti-inflammatory IL-10 cytokine levels. Overall, this study shows that the use of TES without indication or prescription disrupts brain homeostasis, as demonstrated by the increase in neuroinflammation, and that the practice of exercise can protect brain health.
{"title":"Purinergic signaling influences the neuroinflammatory outcomes of a testosterone-derived synthetic in female rats: Resistance training protective effects on brain health","authors":"Aline da Silva Pereira , Nathieli Bianchin Bottari, Jelson Norberto Nauderer, Charles Elias Assmann, Priscila Marquezan Copetti, Karine Paula Reichert, Vitor Bastianello Mostardeiro, Marcylene Vieira da Silveira, Vera Maria Melchiors Morsch, Maria Rosa Chitolina Schetinger","doi":"10.1016/j.steroids.2023.109352","DOIUrl":"10.1016/j.steroids.2023.109352","url":null,"abstract":"<div><p>Physical exercise is recognized as a non-pharmacological approach to treat and protect against several neuroinflammatory conditions and thus to prevent brain disorders. However, the interest in ergogenic resources by athletes and bodybuilding practitioners is widespread and on the rise. These substances shorten the process of performance gain and improve aesthetics, having led to the prominent use and abuse of hormones in the past years. Recent evidence has shown that the purinergic system, composed of adenine nucleotides, nucleosides, enzymes, and receptors, participates in a wide range of processes within the brain, such as neuroinflammation, neuromodulation, and cellular communication. Here, we investigated the effects of the anabolic androgenic steroid (AAS) testosterone (TES) at a dose of 70 mg/kg/week in female rats and the neuroprotective effect of resistance exercise related to the purinergic system and oxidative stress parameters. Our findings showed a decrease in ATP and ADO hydrolysis in treated and trained animals. Furthermore, there was an increase in the density of purinoceptors (P2X7 and A2A) and inflammatory markers (IBA-1, NRLP3, CASP-1, IL-1β, and IL-6) in the cerebral cortex of animals that received AAS. On the other hand, exercise reversed neuroinflammatory parameters such as IBA-1, NLRP3, CASP-1, and IL-1β and improved antioxidant response and anti-inflammatory IL-10 cytokine levels. Overall, this study shows that the use of TES without indication or prescription disrupts brain homeostasis, as demonstrated by the increase in neuroinflammation, and that the practice of exercise can protect brain health.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138831563","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}