Endocrine Abstracts

Dehydroepiandrosterone (DHEA) is the crucial androgen precursor and hyperandrogenaemia is a major feature in Polycystic Ovary Syndrome (PCOS). DHEA sulfate (DHEAS) is generated from DHEA by DHEA sulfotransferase (SULT2A1) activity. The conversion of DHEAS to DHEA by steroid sulfatase has been reported to be of minor significance in human adults and only desulfated DHEA can be converted toward androgens. Therefore, SULT2A1 activity represents the rate-limiting step regulating t...

Mutations in the HSD11B2 gene explain the syndrome of apparent mineralocorticoid excess (AME), which is characterised by severe hypokalemic hypertension. The enzyme product of the HSD11B2 gene, 11-beta hydroxysteroid dehydrogenase type 2 (11beta HSD2), converts cortisol to its inactive form, cortisone. This reaction occurs primarily in the kidney, preventing the mineralocorticoid effects of cortisol, and in the placenta where it is believed to regulate fetal growth by protecti...

11beta-hydroxysteroid dehydrogenase regulates glucocorticoid action, by interconverting cortisone (E) to cortisol (F). The Type 1 isozyme (11betaHSD1) is an oxoreductase expressed in adipose tissue, where it may play a role in the pathogenesis of visceral obesity.We have characterised two polymorphic (CA)n microsatellite markers within intron 4 of the HSD11B1 gene, termed (CA)15 and (CA)19. In an earlier study evaluating a 'normal' population (MONICA co...

A form of congenital adrenal hyperplasia (CAH) is associated with accumulation of steroid metabolites indicating impaired 17alpha-hydroxylase and 21-hydroxylase activities. However, sequencing of CYP17 and CYP21 genes does not reveal mutations, suggesting the involvement of a co-factor interacting with both enzymes. Affected females present with ambiguous genitalia at delivery, but circulating androgens are low and virilisation does not progress, a paradox yet to be explained....

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) catalyses the interconversion of hormonally active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an NADP(H) dependent enzyme expressed in human liver and adipose that is targeted to the ER membrane with a lumenal catalytic domain. In vivo the enzyme acts predominantly as a reductase, generating F from E. The inherited condition, Apparent Cortisone Reductase Deficiency (ACRD) is a form of PCOS characterised by ACTH medi...