Modulation of Growth Hormone-Releasing Factor Stimulated Growth Hormone Secretion by Plasma Glucose and Free Fatty Acid Concentrations in Sheep

Effects of plasma glucose and free fatty acid (FFA) concentrations on bovine growth hormone-releasing factor (bGRF)-induced release of growth hormone (GH) were examined in ovariohysterectomized sheep. In experiment 1, the effects of an infusion of insulin (0.025 U/kg BW·h⁻¹), glucose (40 mg/kg BW·h⁻¹), insulin plus glucose or saline on the subsequent effects of bGRF on plasma GH concentrations were determined. Insulin-induced hypoglycemia inhibited GRF effects on plasma GH concentrations while glucose infusion enhanced bGRF actions. Infusing a higher glucose dose (120 mg/kg BW·h⁻¹) had no effect on GRF actions. Subsequently, infusion of FFA (0.25 g/kg/·h⁻¹), nicotinic acid (50 mg/kg BW) or saline for 1 h prior to bGRF injection demonstrated that FFA inhibited GRF actions but FFA depletion by nicotinic acid infusion had no effect on GRF actions. Nicotinic acid (40 mg/kg BW·h⁻¹) infused for 2 h prior to bGRF injection significantly enhanced bGRF-stimulated GH secretion. Finally, to determine whether central nervous system glucopenia produced similar effects to insulin-induced hypoglycemia, 2-deoxyglucose (500 mg) was injected into the lateral ventricle followed in 1 h by the i.v. injection of bGRF. The central glucopenia produced by 2-DG inhibited GRF-stimulated GH release. These data demonstrate that decreased peripheral or central nervous system glucose availability and exogenous administration of FFA antagonized GRF-induced release of GH. And, pharmacologic depletion of circulating FFA for at least 2 h facilitated GRF-induced release of GH

Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function

Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1(−/−) mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r(−/−) mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence