Endocrine Abstracts

Introduction: Available clinical literature raises the possibility that stress-responsive mechanisms differ by gender, especially in older individuals; however the accompanying evidence is both limited and discrepant. We hypothesize that gender determines the degree of ACTH inhibition by and recovery after an experimental cortisol clamp in older subjects.Subjects and design: We conducted a prospectively randomized, double-blind, placebo-controlled, cross...

Purpose: Available data associate lipids concentrations in men with BMI, anabolic steroids, age, and certain cytokines. Data are less clear in women, especially across the full adult lifespan, and when segmented by pre- and postmenopausal status.Methods: Subjects: 120 healthy women in Olmsted County, MN, USA, a stable well studied clinical population. Dependent variables: measurements of 10-hr fasting high-density lipoprotein cholesterol (HDL-C), total c...

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...

A decade ago, genetic disruption of the kisspeptin signalling pathway was observed to cause hypogonadotrophic hypogonadism. Hypothalamic kisspeptin acts by stimulating secretion of endogenous GnRH. Our research has investigated the physiological effects of kisspeptin in women, with the overarching aim of determining if kisspeptin could be used to treat women with infertility.We initially observed that s.c. bolus injection of kisspeptin acutely stimulated...

Objective: To investigate the effect of pioglitazone on cortisol metabolism in PCOS.Design: Thirty insulin resistant PCOS patients were randomized to either 16 weeks of pioglitazone (30 mg/day) or placebo treatment. Before and after intervention, patients underwent 24 h 20 min.-integrated blood sampling for measurement of cortisol and 24 h excretion of cortisol, cortisone and steroid metabolites (cortisol, corticosteron, androgen, and 17-hydroxyprogester...

LH hyper-secretion, driven by increased GnRH pulsatility, underpins excess testosterone secretion – a key clinical feature of PCOS.The kisspeptin-neurokinin B (NKB)-GnRH pathway has emerged as the pivotal regulator of reproduction. We hypothesised that pharmacologic blockade of NKB may address the central pathophysiology of LH hyper-secretion and hyperandrogenism in PCOS. We undertook a randomised, double blind, placebo-controlled multi-centre Phase...

Background: Women with hypothalamic amenorrhoea (HA) have reduced LH pulsatility causing amenorrhea and infertility. Estrogen supplementation provides symptomatic relief for women with HA, but does not restore the pulsatile pattern of LH secretion which necessary for fertility. Kisspeptin-54 is a recently identified hormone, which potently stimulates GNRH secretion within the hypothalamus. The effect of exogenous kisspeptin-54 administration on LH pulsatility in women with HA ...

Background: The KISS1 gene, is a critical regulator of normal reproductive function. In humans, KISS1 deletion results in a failure to go through puberty while activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep. However chronic exposure to exogenous kisspeptin-54 leads to profound tachyphylaxis in women with hypothalamic amenorrhoea. It is not known whether exogenous kisspeptin can alter the m...

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Background: Hot flushes (HF) affect 70% of menopausal women and can be debilitating. Oestrogen administration is effective but not without risk. Neurokinin B signalling is increased in menopausal women, and is likely critical in the aetiology of their HF. We therefore hypothesised that a neurokinin 3 receptor (NK3R) antagonist could attenuate menopausal flushing.Design: This single-centre, phase 2, randomised, double-blind, placebo-controlled, crossover ...