Effect of Insulin on LHRH Release by Perifused Hypothalamic Fragments

Abstract

Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle’s, pH 7.4, gassed with 95% O₂/5% CO₂, flow rate 50 µl/min). When glucose was absent (in the presence of insulin 10 mU/1), LHRH release was reduced, peak levels being <5 pg/100 µl. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 µl (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/1) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/ 100 µl (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH release.

Effect of Centrally Administered Insulin on Gonadotropin-Releasing Hormone Neuron Activity and Luteinizing Hormone Surge in the Diabetic Female Rat

“…An alternate hypothesis to explain the lack of an LH surge in the presence of sufficient numbers of GnRH-positive staining neurons could be that the lack of insulin attenuates GnRH release into the median eminence. This idea is supported by the findings of Arias et al [22]which showed a direct effect of insulin on GnRH release. Diabetic rats are insulin-deficient and ICV insulin may restore the LH surge by playing a role in the GnRH release mechanism.…”

Insulin in the Brain: Sources, Localization and Functions

“…They have also reported that stimulatory effects of insulin are dependent on the availability of glucose, while acute elevation of glucose level does not affect LHRH release [130]. Consistently, Miller et al showed that intracerebral infusion of insulin to nondiabetic rams also stimulates the luteinizing hormone (LH) pulse frequency, and glucose infusion does not affect gonadotropin secretion [131].…”

“…It has been shown that hypoinsulinemia in diabetic models is accompanied by reduction of LH secretion [130,132], and either systemic acute or chronic insulin administration [132,133] or central insulin supplementation [134] could restore LH pulse frequency in these diabetic individuals. On the other hand, Dong et al showed that insulin loss in diabetic rats not only decreases gonadotropinreleasing hormone (GnRH) release from the hypothalamus, but also in the absence of insulin, the responsiveness of pituitary LH-releasing cells to GnRH is also decreased [132].…”

FAT SUPPLEMENTATION ON REPRODUCTION OF BEEF CATTLE / Suplementação com gordura na reprodução de vacas de corte.

“…The hypothalamus detects the borderline reduction glucose that hinders the release of GnRH (DHUYVETTER & CATON, 1996). Therefore, increasing the gluconeogenesis of the diet could stimulate the secretion of GnRH (RANDEL, 1990) since the combination of glucose and insulin stimulates the release of hypothalamic GnRH (ARIAS et al, 1992). However, insulin administration by subcutaneous injection in beef cattle as well as by intracerebroventricular infusion in ovariectomized sheep does not change the secretion of LH (DHUYVETTER & CATON, 1996).…”