Pub Date : 2003-06-01DOI: 10.1097/00060793-200306000-00007
B. Bausch, Robin D. Munk, J. Schipper, S. Hoegerle, D. Berger, N. Böhm, H. Neumann
&NA; The succinyldehydrogenase subunit D gene (SDHD gene) is a newly recognized susceptibility gene for adrenal pheochromocytoma, extra‐adrenal abdominal and thoracic paraganglioma, and skull basis and neck paraganglioma, known as the paraganglioma syndrome type 1 (PGL1). The SDHD gene is located on chromosome 11q22.3–2.3 and consists of 4 exons. The mutations are spread randomly over all exons and include single amino acid changes and truncations of the gene product by stop codons, deletions, insertions or splice site alterations. Inheritance follows an autosomal‐dominant pattern, but tumors occur only in descendents of fathers carrying the mutation which is consistent with maternal imprinting of the SDHD gene. Patients become symptomatic in the 2nd to 6th decade of life. Major tumor sites are the adrenal medulla and the carotid body. Malignancy is very rare. Treatment of PGL1 is a great challenge and requires abdominal, ENT and thoracic surgery, which should be performed in an atraumatic and whenever possible endoscopic and adrenal‐sparing fashion.
{"title":"SDHD mutations in carotid body tumors and pheochromocytomas: paraganglioma syndrome type 1","authors":"B. Bausch, Robin D. Munk, J. Schipper, S. Hoegerle, D. Berger, N. Böhm, H. Neumann","doi":"10.1097/00060793-200306000-00007","DOIUrl":"https://doi.org/10.1097/00060793-200306000-00007","url":null,"abstract":"&NA; The succinyldehydrogenase subunit D gene (SDHD gene) is a newly recognized susceptibility gene for adrenal pheochromocytoma, extra‐adrenal abdominal and thoracic paraganglioma, and skull basis and neck paraganglioma, known as the paraganglioma syndrome type 1 (PGL1). The SDHD gene is located on chromosome 11q22.3–2.3 and consists of 4 exons. The mutations are spread randomly over all exons and include single amino acid changes and truncations of the gene product by stop codons, deletions, insertions or splice site alterations. Inheritance follows an autosomal‐dominant pattern, but tumors occur only in descendents of fathers carrying the mutation which is consistent with maternal imprinting of the SDHD gene. Patients become symptomatic in the 2nd to 6th decade of life. Major tumor sites are the adrenal medulla and the carotid body. Malignancy is very rare. Treatment of PGL1 is a great challenge and requires abdominal, ENT and thoracic surgery, which should be performed in an atraumatic and whenever possible endoscopic and adrenal‐sparing fashion.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"10 1","pages":"197–204"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-200306000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1097/01.med.0000224811.39318.73
W. Arlt, B. Allolio
Purpose of reviewThe option of dehydroepiandrosterone (DHEA) replacement has attracted considerable attention from rather different perspectives over recent years. This review summarizes recent findings from randomized controlled trials. Recent findingsThe clinical impact of DHEA replacement was defined in patients with adrenal insufficiency, the pathophysiological model population for complete DHEA deficiency, and recent studies have confirmed beneficial effects of health-related quality of life and mood. The neurosteroidal properties of DHEA suggest anti-depressant action and several studies in patients with neuropsychiatric disorders have confirmed this. Important advances have been made regarding the use of DHEA in patients with chronic autoimmune disease, DHEA treatment in systemic lupus erythematosus in phase II and III trials has resulted in reduced disease activity, reduction in glucocorticoid dosage and maintenance of bone mineral density. SummaryDHEA is a useful tool for female androgen replacement, in particular in women with adrenal insufficiency. Its neurosteroidal properties merit further studies in depressive disorders and anorexia nervosa. Studies in systemic lupus erythematosus have begun to define the usefulness of DHEA as a therapeutic, immune modulatory drug. Caution is required, however, regarding the use of DHEA in healthy elderly persons as current evidence does not justify the use of DHEA in this context.
{"title":"Dehydroepiandrosterone replacement therapy","authors":"W. Arlt, B. Allolio","doi":"10.1097/01.med.0000224811.39318.73","DOIUrl":"https://doi.org/10.1097/01.med.0000224811.39318.73","url":null,"abstract":"Purpose of reviewThe option of dehydroepiandrosterone (DHEA) replacement has attracted considerable attention from rather different perspectives over recent years. This review summarizes recent findings from randomized controlled trials. Recent findingsThe clinical impact of DHEA replacement was defined in patients with adrenal insufficiency, the pathophysiological model population for complete DHEA deficiency, and recent studies have confirmed beneficial effects of health-related quality of life and mood. The neurosteroidal properties of DHEA suggest anti-depressant action and several studies in patients with neuropsychiatric disorders have confirmed this. Important advances have been made regarding the use of DHEA in patients with chronic autoimmune disease, DHEA treatment in systemic lupus erythematosus in phase II and III trials has resulted in reduced disease activity, reduction in glucocorticoid dosage and maintenance of bone mineral density. SummaryDHEA is a useful tool for female androgen replacement, in particular in women with adrenal insufficiency. Its neurosteroidal properties merit further studies in depressive disorders and anorexia nervosa. Studies in systemic lupus erythematosus have begun to define the usefulness of DHEA as a therapeutic, immune modulatory drug. Caution is required, however, regarding the use of DHEA in healthy elderly persons as current evidence does not justify the use of DHEA in this context.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"13 1","pages":"291–305"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/01.med.0000224811.39318.73","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61655827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00005
W. Rainey, P. White
Aldosterone is an important regulator of fluid and electrolyte balance. The capacity of the adrenal gland to produce aldosterone is controlled by circulating levels of angiotensin II and potassium, which regulate the expression of aldosterone synthase (CYP11B2). This enzyme catalyzes the final steps of aldosterone synthesis and is expressed only in the zona glomerulosa of the adrenal cortex. The development of new systems for in vitro studies of expression has helped to define the molecular mechanisms that regulate this enzyme and thus the capacity of the adrenal gland to produce aldosterone. Both potassium and angiotensin II increase intracellular calcium levels, which regulate expression of CYP11B2 through transcription factors that interact with defined sites in the 5-flanking region of the gene.
{"title":"Functional adrenal zonation and regulation of aldosterone biosynthesis","authors":"W. Rainey, P. White","doi":"10.1097/00060793-199806000-00005","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00005","url":null,"abstract":"Aldosterone is an important regulator of fluid and electrolyte balance. The capacity of the adrenal gland to produce aldosterone is controlled by circulating levels of angiotensin II and potassium, which regulate the expression of aldosterone synthase (CYP11B2). This enzyme catalyzes the final steps of aldosterone synthesis and is expressed only in the zona glomerulosa of the adrenal cortex. The development of new systems for in vitro studies of expression has helped to define the molecular mechanisms that regulate this enzyme and thus the capacity of the adrenal gland to produce aldosterone. Both potassium and angiotensin II increase intracellular calcium levels, which regulate expression of CYP11B2 through transcription factors that interact with defined sites in the 5-flanking region of the gene.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"175–182"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00002
W. Miller
Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe of the CAH syndromes, eliminating virtually all adrenal and gonadal steroid hormone synthesis. Previously regarded as a rare, esoteric condition, lipoid CAH has recently received considerable attention since the discovery that lipoid CAH was caused by mutations in the gene for the steroidogenic acute regulatory protein (StAR), and the demonstration that the disease is fairly common in Japan. Clinical studies of lipoid CAH substantially illuminated the biology of the StAR protein, as lipoid CAH constitutes a StAR gene knockout experiment of nature. Studies of lipoid CAH showed that steroidogenic cells employ both StAR-dependent and StAR-independent modes of steroidogenesis. This in turn indicated that the lipoid CAH phenotype was due to two events: first, a loss of StAR-dependent steroidogenesis led to diminished steroidogenesis and to cellular accumulation of cholesterol esters; second, cellular damage caused by this accumulation eliminated StAR-independent steroidogenesis. This two-hit model of lipoid CAH explains the variable onset of salt loss and the presence of apparently normal pubertal feminization in affected 46,XX females. However, the mechanism of StAR's action to promote the flow of cholesterol into mitochondria remains unknown.
{"title":"Lessons from congenital lipoid adrenal hyperplasia","authors":"W. Miller","doi":"10.1097/00060793-199806000-00002","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00002","url":null,"abstract":"Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe of the CAH syndromes, eliminating virtually all adrenal and gonadal steroid hormone synthesis. Previously regarded as a rare, esoteric condition, lipoid CAH has recently received considerable attention since the discovery that lipoid CAH was caused by mutations in the gene for the steroidogenic acute regulatory protein (StAR), and the demonstration that the disease is fairly common in Japan. Clinical studies of lipoid CAH substantially illuminated the biology of the StAR protein, as lipoid CAH constitutes a StAR gene knockout experiment of nature. Studies of lipoid CAH showed that steroidogenic cells employ both StAR-dependent and StAR-independent modes of steroidogenesis. This in turn indicated that the lipoid CAH phenotype was due to two events: first, a loss of StAR-dependent steroidogenesis led to diminished steroidogenesis and to cellular accumulation of cholesterol esters; second, cellular damage caused by this accumulation eliminated StAR-independent steroidogenesis. This two-hit model of lipoid CAH explains the variable onset of salt loss and the presence of apparently normal pubertal feminization in affected 46,XX females. However, the mechanism of StAR's action to promote the flow of cholesterol into mitochondria remains unknown.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"155–161"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00004
B. Walker
In clinical practice we measure cortisol in plasma and urine and treat disorders of cortisol secretion. In research, extensive studies have dissected the factors that influence the hypothalamic-pituitary-adrenal axis and modulate cortisol secretion. In recent years, however, the research focus has turned toward factors influencing tissue sensitivity to cortisol, both in sites responsible for negative feedback and in peripheral tissues. Key observations include the cloning of glucocorticoid and mineralocorticoid receptors, dissection of their signaling pathways, and recognition of the importance of cortisol metabolism in modulating tissue sensitivity. This article reviews recent data that illustrate the extent to which these research findings are now being applied in clinical practice, addresses the question of whether intrinsic sensitivity to glucocorticoids varies between individuals, and emphasizes the important impact on health and on responsiveness to glucocorticoid therapy.
{"title":"Glucocorticoid sensitivity in humans","authors":"B. Walker","doi":"10.1097/00060793-199806000-00004","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00004","url":null,"abstract":"In clinical practice we measure cortisol in plasma and urine and treat disorders of cortisol secretion. In research, extensive studies have dissected the factors that influence the hypothalamic-pituitary-adrenal axis and modulate cortisol secretion. In recent years, however, the research focus has turned toward factors influencing tissue sensitivity to cortisol, both in sites responsible for negative feedback and in peripheral tissues. Key observations include the cloning of glucocorticoid and mineralocorticoid receptors, dissection of their signaling pathways, and recognition of the importance of cortisol metabolism in modulating tissue sensitivity. This article reviews recent data that illustrate the extent to which these research findings are now being applied in clinical practice, addresses the question of whether intrinsic sensitivity to glucocorticoids varies between individuals, and emphasizes the important impact on health and on responsiveness to glucocorticoid therapy.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"168–174"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00006
M. Zennaro, M. Lombès
Since the first cloning of members of the nuclear receptor superfamily, it has become evident that different isoforms are generated from single genes by various mechanisms such as utilization of alternative promoters, alternative splicing, and use of different translation initiation or polyadenylation sites. Different mineralocorticoid receptor mRNA isoforms have been identified in human and rat, which are submitted to tissue-specific expression and regulation. Recent studies indicate the existence of receptor variants with putative different functional properties, which could account for differences in target cell responsiveness to hormones. We review molecular mechanisms involved in generation of mRNA or protein isoforms and discuss the potential physiopathologic implications of mineralocorticoid receptor variants.
{"title":"Mineralocorticoid receptor isoforms","authors":"M. Zennaro, M. Lombès","doi":"10.1097/00060793-199806000-00006","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00006","url":null,"abstract":"Since the first cloning of members of the nuclear receptor superfamily, it has become evident that different isoforms are generated from single genes by various mechanisms such as utilization of alternative promoters, alternative splicing, and use of different translation initiation or polyadenylation sites. Different mineralocorticoid receptor mRNA isoforms have been identified in human and rat, which are submitted to tissue-specific expression and regulation. Recent studies indicate the existence of receptor variants with putative different functional properties, which could account for differences in target cell responsiveness to hormones. We review molecular mechanisms involved in generation of mRNA or protein isoforms and discuss the potential physiopathologic implications of mineralocorticoid receptor variants.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"183–188"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00003
J. Honour
There is little direct evidence from viral culture for HIV infection in the adrenal glands, but infiltration of endocrine tissues by opportunistic infection or malignancy is common. Loss of adrenocortical function can be difficult to assess, particularly when medications used in the treatment of opportunistic infections result in hormonal or metabolic disturbances. In most cases basal cortisol levels indicate that adrenal function is normal for desperately ill patients. Standard provocative tests, however, may reveal subtle abnormalities of adrenal and pituitary hormone production. Changes in adrenal steroidogenesis do occur, with the result that cortisol production is favored over adrenal androgen and miner-alocorticoid production. Adrenal reserve can be limited. An acquired glucocorticoid resistance may explain high cortisol levels in some cases. Complex interactions between the endocrine and immune systems may influence the progression of HIV infection to AIDS. Further research is necessary to clarify these interactions.
{"title":"HIV and adrenal function","authors":"J. Honour","doi":"10.1097/00060793-199806000-00003","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00003","url":null,"abstract":"There is little direct evidence from viral culture for HIV infection in the adrenal glands, but infiltration of endocrine tissues by opportunistic infection or malignancy is common. Loss of adrenocortical function can be difficult to assess, particularly when medications used in the treatment of opportunistic infections result in hormonal or metabolic disturbances. In most cases basal cortisol levels indicate that adrenal function is normal for desperately ill patients. Standard provocative tests, however, may reveal subtle abnormalities of adrenal and pituitary hormone production. Changes in adrenal steroidogenesis do occur, with the result that cortisol production is favored over adrenal androgen and miner-alocorticoid production. Adrenal reserve can be limited. An acquired glucocorticoid resistance may explain high cortisol levels in some cases. Complex interactions between the endocrine and immune systems may influence the progression of HIV infection to AIDS. Further research is necessary to clarify these interactions.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"162–167"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00007
C. Gicquel, Y. Bouc, J. Luton, X. Bertagna
Therapy for adrenocortical carcinoma remains frustratingly problematic, and the prognosis for affected patients is dismal. Recent attempts to better understand the biology of these tumors have unraveled a number of abnormalities. Some features appear merely to reflect the growth potential of these tumors and loss of differentiated functions, whereas others may play a pathogenetic role. Particularly interesting is the frequent genetic turmoil at the 11 p15 locus, resulting in loss of the maternal allele and duplication of the paternal allele. This chromosomal region bears imprinted genes that are probably involved in the fine tuning of adrenocortical cell proliferation: antioncogenes (eg, p57K/P2 and H19) and growth factors (eg, insulinlike growth factor-ll). These studies have revealed new molecular markers of the malignant phenotype that markedly improve the diagnosis of and prognosis for adrenocortical carcinoma. Genotyping of adrenocortical tumors will probably become more widely used and even obligatory for selecting patients for participation in trials of adjuvant chemotherapy after apparent curative surgery.
{"title":"Pathogenesis and treatment of adrenocortical carcinoma","authors":"C. Gicquel, Y. Bouc, J. Luton, X. Bertagna","doi":"10.1097/00060793-199806000-00007","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00007","url":null,"abstract":"Therapy for adrenocortical carcinoma remains frustratingly problematic, and the prognosis for affected patients is dismal. Recent attempts to better understand the biology of these tumors have unraveled a number of abnormalities. Some features appear merely to reflect the growth potential of these tumors and loss of differentiated functions, whereas others may play a pathogenetic role. Particularly interesting is the frequent genetic turmoil at the 11 p15 locus, resulting in loss of the maternal allele and duplication of the paternal allele. This chromosomal region bears imprinted genes that are probably involved in the fine tuning of adrenocortical cell proliferation: antioncogenes (eg, p57K/P2 and H19) and growth factors (eg, insulinlike growth factor-ll). These studies have revealed new molecular markers of the malignant phenotype that markedly improve the diagnosis of and prognosis for adrenocortical carcinoma. Genotyping of adrenocortical tumors will probably become more widely used and even obligatory for selecting patients for participation in trials of adjuvant chemotherapy after apparent curative surgery.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"189–196"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1097/00060793-199806000-00001
Z. Krozowski
Cortisol has a number of surprising abilities. Perhaps the most interesting of these is its ability to bind to the mineralocorticoid receptor with an affinity equivalent to that of aldosterone. In sodium-transporting epithelia, 11β-hydroxysteroid dehydrogenase type 2(11βHSD2) converts cortisol to the receptor-inactive cortisone, allowing aldosterone to bind to its receptor in the setting of much higher circulating levels of glucocorticoid. Mutations in 11βHSD2 account for the congenital syndrome of apparent mineralocorticoid excess (AME), a low-renin, life-threatening form of hypertension resulting from overstimulation of the mineralocorticoid receptor by cortisol in the distal tubule of the kidney. The receptor and enzyme also colocalize in the gut, the sweat glands, and the lung. There is increasing evidence that the actions of 11βHSD2 also play an important role in other physiologic processes, notably reproduction. In the placenta, 11βHSD2 protects the fetus from high levels of maternal glucocorticoids; in other tissues, high localized levels of the enzyme lower the intracellular levels of glucocorticoids in specialized cells such as the nonluteinized granulosa cells of the human ovary and the epithelial cells of the endometrium, suggesting that fertility may also be affected in patients with AME. The extent to which these tissues are affected will be determined, inter alia, by the presence of other yet undiscovered oxidative isoforms of 11β-hydroxysteroid dehydrogenase.
{"title":"Cardiovascular and other effects of 11β-hydroxysteroid dehydrogenase type 2 and the syndrome of apparent mineralocorticoid excess","authors":"Z. Krozowski","doi":"10.1097/00060793-199806000-00001","DOIUrl":"https://doi.org/10.1097/00060793-199806000-00001","url":null,"abstract":"Cortisol has a number of surprising abilities. Perhaps the most interesting of these is its ability to bind to the mineralocorticoid receptor with an affinity equivalent to that of aldosterone. In sodium-transporting epithelia, 11β-hydroxysteroid dehydrogenase type 2(11βHSD2) converts cortisol to the receptor-inactive cortisone, allowing aldosterone to bind to its receptor in the setting of much higher circulating levels of glucocorticoid. Mutations in 11βHSD2 account for the congenital syndrome of apparent mineralocorticoid excess (AME), a low-renin, life-threatening form of hypertension resulting from overstimulation of the mineralocorticoid receptor by cortisol in the distal tubule of the kidney. The receptor and enzyme also colocalize in the gut, the sweat glands, and the lung. There is increasing evidence that the actions of 11βHSD2 also play an important role in other physiologic processes, notably reproduction. In the placenta, 11βHSD2 protects the fetus from high levels of maternal glucocorticoids; in other tissues, high localized levels of the enzyme lower the intracellular levels of glucocorticoids in specialized cells such as the nonluteinized granulosa cells of the human ovary and the epithelial cells of the endometrium, suggesting that fertility may also be affected in patients with AME. The extent to which these tissues are affected will be determined, inter alia, by the presence of other yet undiscovered oxidative isoforms of 11β-hydroxysteroid dehydrogenase.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"5 1","pages":"149–154"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199806000-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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