Endocrine Abstracts

It is becoming increasingly evident that pathways exist within the (ER) that can impact upon cellular redox status, glucocorticoid metabolism and glucose homeostasis.Within the ER of the liver, glucose-6-phosphatase (G6Pase) and glucose 6-phosphate (G6P) transporter (G6PT) work together to increase blood glucose concentrations by performing the terminal step in both glycogenolysis and gluconeogenesis. The G6Pase ‘shares’ G6P with hexose-6-phosp...

Harvey Cushing’s work informed us of the deleterious consequences of circulating cortisol excess – hypertension, osteoporosis and obesity that contributes to diabetes and premature mortality. Conversely, Hench, Kendall and Reichstein were Nobel Laureates in Physiology 1950 for the discovery of cortisone and demonstrating efficacy in patients with Rheumatoid Arthritis – in effect the birth of the anti-inflammatory actions of glucocorticoids.<p class="abstext"...

Murine 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses the conversion of inactive 11-dehydrocorticosterone (A) to active corticosterone (B) and plays a key role in metabolic homeostasis. The directionality of this enzyme is dependent upon the presence of NADPH, a cofactor produced by hexose-6-phosphate dehydrogenase (H6PDH). In accord with this, H6PDH KO mice have no reductase and increased dehydrogenase activity of 11βHSD1. Interestingly, H6PDH KO m...

Glucocorticoid excess results in central obesity and insulin resistance/diabetes mellitus. At a pre-receptor level, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) modulates glucocorticoid levels and has been implicated in the pathogenesis of the metabolic syndrome. 11beta-HSD1 is a bi-directional NADP(H) dependant enzyme, but keto-reductase activity predominates in-vivo. Recent studies indicate that the enzyme H6PDH ensures reductive metabolism (cortisone to c...

Little is known about the factors affecting preantral follicle growth but we have recently shown that IGF-I stimulates growth of follicles in human cortical tissue in culture (Stubbs et al, Endocrine Abstracts 2003, 6, OC7). The aim of this study was to extend the study of the effects of IGF-I on follicle recruitment and test the specificity of action by examining the ability of the type 1 IGF receptor antibody, alpha-IR3, to inhibit IGF action. Small ovarian cortical biopsies...

Little is known about the factors affecting preantral follicle growth but we have recently shown that IGF-I stimulates growth of follicles in human cortical tissue in culture (Stubbs et al, Endocrine Abstracts 2003, 6, OC7). The aim of this study was to extend the study of the effects of IGF-I on follicle recruitment and test the specificity of action by examining the ability of the type 1 IGF receptor antibody, alpha-IR3, to inhibit IGF action. Small ovarian cortical biopsies...

Little is know about the effects of IGFs on the early preantral stages of follicle development. The aim of this study was to investigate the effects of IGF-I on recruitment and survival of human preantral follicles in vitro. Small ovarian cortical biopsies were obtained at laparoscopy, with informed consent and local ethical committee approval, from 27 premenopausal women. The tissue was divided and randomly allocated to 5 conditions. The first piece was fixed immediately as a...

Early follicular development in polycystic ovaries (PCO) is abnormal; a higher proportion of follicles have entered the growing phase than in normal ovaries [1]. IGF-I stimulates the initiation of preantral follicle growth in a human tissue culture system using a growth factor-reduced extracellular matrix, Matrigel [2]. The aim of this study was to compare the effects of IGF-I on early preantral follicle development in polycystic and normal ovaries. Small ovarian cortical biop...

Mutations in the HSD11B2 gene explain the syndrome of apparent mineralocorticoid excess (AME), which is characterised by severe hypokalaemic hypertension. Cortisol acts as a mineralocorticoid through failure of its inactivation to cortisone by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Patients are diagnosed by a raised THF+allo-THF/THE ratio. To date, approximately 30 mutations have been described in HSD11B2. Recently, three apparently unrelated kindreds with A...

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...