Endocrine Abstracts

Annexin 1 (ANXA1) plays an essential role in the 'early-delayed' feedback effects of glucocorticoids (GCs) on ACTH release. Evidence that ANXA1 is externalised from pituitary cells in response to GCs, together with the finding that the protein is localised mainly to the folliculo-stellate (FS) cells, has led us to propose that ANXA1 is a paracrine mediator of GC action in the anterior pituitary. To address this hypothesis we have examined ANXA1-dependent GC actions in co-cultu...

Our previous studies have shown that the acute regulatory actions of glucocorticoids (GCs) on the secretion of corticotrophin (ACTH) are dependent upon the translocation of a 37 kDa protein, annexin 1 (ANXA1 [1]) from within the cell to the outer cell surface where it is retained by a Ca2+-dependent mechanism (2). The mechanisms by which ANXA1 is exported from pituitary cells in response to a steroid challenge and acts on the endocrine cells to suppress peptide rele...

(Will also be presented as a Steroids poster)Alpha-melanocyte-stimulating-hormone (alpha-MSH) is an agonist at the melanocortin-3-receptor (MC3-R) and the MC4-R. It stimulates corticosterone release from rat adrenal glomerulosa cells. The receptor mediating this effect is unidentified since only MC2-R and MC5-R have been reported to be expressed in the adrenal and alpha-MSH is a poor agonist at these receptors. Agrp, an endogenous antagonist at the MC3-R...

Human skin is a target tissue for circulating androgens released from the adrenal glands and gonads but local steroid production may also occur in human skin. StAR is a cholesterol transporter protein that controls the rate-limiting step in steroid synthesis and is regulated by steroidogenic factor (SF-1) in the adrenal glands. We have demonstrated the expression of StAR mRNA by RT-PCR in primary dermal papilla cells and in the immortalised human keratinocyte cell line HaCaT. ...

In human granulosa-lutein (hGL) cells, cortisol (F) is inter-converted with cortisone (E) by 11BHSD. To date two isoforms of 11BHSD have been cloned. Human granulosa cells have been shown to express 11BHSD2 mRNA during the follicular phase of the ovarian cycle, switching to 11BHSD1 mRNA expression as luteinization occurs. However, it is not known whether (1) the protein expression, and (2) the 11BHSD enzyme activities reflect this pattern of mRNA expression. Hence, the aims of...

The physiological effects of the pituitary hormone, adrenocorticotropic hormone (ACTH) on the adrenal are mediated by the melanocortin 2 receptor (MC2R), a G protein coupled receptor (GPCR) that signals via adenylate cyclase to elevate intracellular cyclic AMP (cAMP) levels. Therefore the expression and function of the receptor are likely to be the major determinants of the response to ACTH. Following repeated stimulation, the cAMP signal is diminished or desensitised. Desensi...

The excess androgen levels in women with PCOS may be ovarian and/or adrenal in origin and one proposed contributing mechanism is an alteration in cortisol metabolism. Increased peripheral cortisol metabolism, either by enhanced inactivation of cortisol by 5alpha-reductase or impaired reactivation of cortisol by 11b-hydroxysteroid dehydrogenase (11bHSD type 1), results in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations...

In a double-blind study, 106 patients (44 males, 62 females, age 20-64 years) with Addison's disease, were randomised to receive either 50mg of micronised DHEA or placebo orally daily for 12 months. Psychological and biochemical parameters were measured at baseline, 3 to 6 month intervals and post-washout; bone mineral density (BMD) and body composition were assessed by DEXA at baseline and 12 months.DHEAS levels rose significantly and were maintained th...