Endocrine Abstracts

During the luteal phase of the menstrual cycle aldosterone increases mainly due to the antagonistic properties of progesterone at the MR and due to estrogen-mediated stimulation of angiotensinogen. Little is known about other steroid-metabolizing enzymes that may influence steroid receptor binding, eg 11beta-HSDs, A-ring reductases. Therefore a group of ten normotensive female volunteers with regular menstrual cycles were studied on day 7 (follicular phase) and day 21 (luteal ...

It is now evident that ghrelin is more than just a growth hormone (GH) secretagogue; it plays an important role in energy homeostasis, increasing food intake and fat deposition, has cardiovascular effects, and inhibits cell proliferation.Ghrelin mRNA expression is widespread in human tissues, but little is known about the molecular mechanisms and signals that regulate gene expression at the transcriptional level. To address this we cloned and sequenced a 4kb region upstrea...

Ghrelin, the natural ligand for the GHS-R, modulates proliferation in cell lines derived from malignant breast tissue. It has been suggested that this action is independent of the GHS-R. We have previously demonstrated that MCF7 cells expressed ghrelin but not GHS-R mRNA and MDA-MB231 cells expressed GHS-R but not ghrelin mRNA. To determine whether ghrelin modulates proliferation in MCF7 and MDA-MB231 cells we performed proliferation assays treating with saline, 1 and 10nM ghr...

Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with insulin resistance in a large PCOS cohort.We compared results from 127 PCOS patients (Rotterdam criteria) with 100 BMI-matched controls. All subjects under...

GH deficiency (GHD) in adults shares several clinical features with syndromes of glucocorticoid excess. Many patients with GHD also receive glucocorticoid therapy. GH inhibits the generation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), but the confounding effect of ACTH deficiency/ cortisol replacement therapy has not been evaluated.Aims: To assess corticosteroid exposure and metabolism and body composition in...

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...

Glucocorticoid treatment in congenital adrenal hyperplasia (CAH) is a continuous challenge, with even the experienced clinician struggling to strike the right balance between glucocorticoid over- and undertreatment. There is no consensus on monitoring of glucocorticoid therapy in adults with CAH. Some recommend a serum 17-hydroxyprogesterone (17OHP) target range of 12–36 nmol/l prior to glucocorticoid morning dose. Here we investigated the value of serum and urinary stero...

Mitotane (o,p’DDD) is commonly used for the treatment of adrenocortical carcinoma (ACC), both for advanced disease and in the adjuvant setting. Mitotane induces adrenal insufficiency but specific effects on steroidogenic enzymes are unknown.We investigated 24-h urinary steroid metabolite excretion in ACC patients on adjuvant mitotane (AD) or mitotane for metastatic disease (MET). We compared samples collected before mitotane treatment (BEFORE; MET <...