Endocrine Abstracts

The central role of GnRH in gonadotropin was established over four decades ago. The development of agonist and antagonist analogs and the understanding of its interaction with the GnRH receptor has revolutionized the treatment of hormone-dependent diseases and controlled induction of ovulation for IVF.The absence of steroid and metabolic product receptors in GnRH neurons has presented a conundrum for understanding feedback and mechanisms for gonadotropin...

The discovery of GnRH involved extraordinary insight, determination and creativity as well as conflict and competition where the players inadvertently advanced each other’s endeavours. However, many of us experienced great collegiality, collaboration and sharing reagents in these halcyon years. Many colourful and ambitious characters were involved in the recognition that a portal system transferred a factor from the brain to the pituitary supported by elegant experiments ...

The development and maturation of kisspeptin neurons is critical for activating GnRH release needed to initiate puberty. However, little is known of the development and organization of kisspeptin neurons in the human hypothalamus and the anatomical architecture of kisspeptin neurons in rodents is distinct from that of primates.The aim of the present study was to examine the development of the hypothalamic neuroendocrine circuitry that sets the structural...

The mammalian Forkhead Box O (FoxO) transcription factors, FoxO1, FoxO3a and FoxO4 are emerging as an important family of proteins that modulate the expression of genes involved in cell cycle regulation, induction of apoptosis, DNA damage repair and response to oxidative stress. Their transcriptional activity is tightly regulated by the action of several regulatory co-factors, and a series of post-translational modifications controlling a shuttling system, that confines them e...

Hypothesis: Exogenous kisspeptin-10 (Kp10) enhances pulsatile LH. Research strategy: A first-in-man dosing study of kp10 was first performed. Healthy volunteers and hypogonadal patients were subsequently infused with kp10. Dose titration study Rapid increases in LH with clear dose-dependency (P<0.0001) were observed in healthy men (n=6), with the 0.3 and 1 µg/kg doses being maximally stimulatory (P<0.01). Effect of sex-steroid milieu: LH respo...

G protein-coupled receptors (GPCRs) are critical for signal transduction within neuroendocrine signalling pathways, and genetic mutations in G protein-coupled GPCRs underlie numerous diseases. Inactivating GPCR mutations can impede ligand interactions or signal transduction, or can result in misfolding of nascent receptor proteins and subsequent retention in the endoplasmic reticulum (ER) and thus failure to traffic to the cell surface. Examination of the functionality and cel...

Background: Large populations of HIV and tuberculosis occur in South Africa and, amongst these patients, Addison’s disease is probably underdiagnosed. Preliminary data in 60 HIV-positive patients with a CD4 count less than 100 cells/mm3 showed that the overall prevalence of hypoadrenalism was 6.7%, with 1 patient having primary hypoadrenalism and 3 patients having central hypoadrenalism. This report describes the prevalence of hypoadrenalism and its association...

Background: Addison’s disease is probably under-diagnosed in South Africa, given that the prevalence is considerably lower than reported in Western countries (Chabre O 2017); this is important as patients may be dying from a highly treatable condition. In addition, large populations of HIV and tuberculosis infected patients in South Africa may have some symptoms erroneously attributed to these conditions, rather than Addison’s disease. We determined the prevalence an...

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative ‘hot spot&#...