Endocrine Abstracts

Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2...

Progesterone (P4) treatment has been shown to have a clear modulating effect on murine Leydig tumor cell (mLTC-1) function, including downregulation of luteinizing hormone receptor. We hypothesized that P4 would stimulate, whereas an antiprogestine mifepristone (MF) block tumor progression in vivo in a transgenic (TG) murine Leydig cell tumor model (inhibin-α promoter-driven SV40 T-antigen (inhα/Tag)) and act similarly on cell proliferation in vitro...

Background: Data examining HLA associations in Addison’s disease (AD) from South Africa (SA) are limited. We wished to determine the HLA in South African AD patients either positive or negative for 21 hydroxylase autoantibodies (21 OH-AA) and matched healthy controls, hypothesising that certain HLA alleles could predominate, but there may be differences from Western countries.Methods: SA patients (n=73) were enrolled as part of a nationwide...

Antiprogestine mifepristone (MF) has been shown to inhibit ovarian epithelial cancer (OEC) cell growth in vitro and in vivo. Recent clinical trials with MF for human OEC were unsuccessful, for unknown reasons. Progesterone (P4) is believed to have preventive measures towards breast, endometrial or hOEC cancers. Hereby we analyzed the effects of P4 and MF on ovarian granulosa cell tumorigenesis (GCT) in vitro and in vivo...

The overproduction of ACTH, in conditions such as Congenital Adrenal Hyperplasia (CAH) leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment that would directly block ACTH action. Such a therapy, especially one that can be orally administered, would be of great clinical value allowing a ‘block and replace’ tre...

Bile acids (BAs) are synthesized by converting cholesterol in hepatocytes and recycling it via enterohepatic circulation. Most BAs are reabsorbed into hepatocytes, where they inhibit their own synthesis by activating FXR pathway. NTCP is a major transporter of BAs via absorption from portal blood into hepatocytes. Hepalatide is a 47aa synthetic peptide that specifically binds NTCP resulting in BA spillover of hepatocytes into the systemic circulation. In this way, BA synthesis...

Objective: To report a rare cause of ectopic adrenocorticotropic hormone (ACTH) secretion leading to Cushing syndrome.Methods: We describe the clinical presentation and management of a case of Cushing syndrome attributable to ectopic ACTH secretion from small cell cancer of the prostate.Results: In a 74-year-old man developed hypocalemia and heart failure. He was found to have severe hypokalemia (serum potassium, 2.37 mEq/l). Hormo...

Introduction: The effect of BMI on mortality amongst the elderly may be different from younger adults. Thus, this study aims to determine the relationship between BMI and its 5-year changes on all-cause and cause-specific mortality in the elderly.Methods: During 1992–1994, the Blue Mountains Eye Study recruited 3654 residents aged ≥49 years in Sydney, Australia. Of these, 75% of survivors returned for follow-up at 5 years. We initially examine...

Objective: To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was worthwhile to do in type 1 diabetes adolescents with diabetic ketoacidosis at diagnosis.Research Design and Methods: We enrolled 28 type 1 diabetes patients aged 14–30 years in a prospective AHSCT phase II clinical trial. Hematopoietic stem cells were harvested from the peripheral blood following a pretreatment consisting of a combination of cy...

We have earlier shown a reciprocal feed-forward amplification link between expression of transcription factor GATA-4 and luteinizing hormone receptor (LHR) during adrenocortical tumorigenesis, and also that chronically elevated LH levels may induce LHR in mice, but not GATA-4. Hereby, our goal was to analyze the consequences of ectopically expressed GATA-4 on murine adrenal cortex in the presence and absence of gonadectomy (GDX) induced elevated LH levels. For this purpose, we...