Insulin-Induced Hypoglycemia Decreases Luteinizing Hormone Secretion in the Castrated Male Rat: Involvement of Opiate Peptides

Abstract

Insulin-induced hypoglycemia (ΠH) has been reported to inhibit luteinizing hormone (LH) secretion in ovariectomized ewes as well as in intact or gonadectomized female rhesus monkeys. An infusion of naloxone, a specific opiate receptor antagonist, while able to prevent this inhibitory effect in ewes, was ineffective in monkeys, suggesting a difference in the mechanisms involved in the response to IIH in these two species. The present study was designed to investigate the influence of this stimulus on the dynamics of LH release and the possible activation of an opioidergic pathway in the long-term castrated male rat. Blood samples were collected every 7 min, for several hours, in freely-moving rats bearing a jugular cannula. The intravenous injection of 0.4 IU of insulin triggered an acute hypoglycemia and reduced LH release. In contrast, during a continuous intravenous naloxone infusion (0.5 mg/kg/h), insulin, while still lowering the glycemia, failed to affect the LH secretory pattern. In a control experiment, naloxone infusion alone had no significant effect on mean LH concentration and pulse intervals. These experiments indicate that, in long-term gonadectomized male rats, IIH impairs the LH secretory pattern, and that endogenous opioid peptides are involved in this response.

Effects of Estradiol on Glucoprivic Transactivation of Catecholaminergic Neurons in the Female Rat Caudal Brainstem

“…While E is reported to decrease glucoprivic feeding [11]and enhance inhibitory effects of glucose deficits on pituitary gonadotropin secretion [12, 13], the central site(s) at which this hormone acts to modulate these compensatory responses to glucopenia have not yet been identified. The present findings that E enhances glucoprivic transactivation of LC, NTS, and AP neurons suggest that one or more of these loci may serve as substrates for steroidal effects on acute motor activities elicited by glucopenia and/or adaptive cellular responses to energy deficits.…”

“…The ovarian steroid estradiol (E) influences net energy balance through regulatory effects on nutrient intake, lipolysis, thermogenesis, and basal metabolic rate [10], and modulates the magnitude of feeding and pituitary gonadotropin responses to 2DG [11, 12, 13]. E secretion fluctuates over the estrous cycle in adult female rats, with peak hormone concentrations occurring during mid-proestrus and plasma levels subsequently falling to a nadir during metestrus [14, 15].…”

Glucoreceptors Located Inside the Blood-Brain Barrier Mediate Hypoglycemia-Induced LH Inhibition in Man

“…Insulin-induced hypoglycemia is known to inhibit luteinizing hormone (LH) secretion in various animal species and in humans [1, 2, 3, 4, 5, 6, 7, 8]. Even though it has been hypothesized that during hypoglycemia insulin itself may have a neuromodulatory effect on LH secretion, recent experiments in men suggest that hypoglycemia, rather than insulin, is responsible for the inhibition of LH secretion by acting on hypothalamic glucoreceptors [8].…”

Simultaneous Observation of the GnRH Pulse Generator Activity and Plasma Concentrations of Metabolites and Insulin during Fasting and Subsequent Refeeding Periods in Shiba Goats

“…Several lines of evidence suggest that blood-borne energy substrates or metabolic hormones, such as insulin, signal the mechanism generating pulsatile GnRH and LH release to control gonadal activity [8][9][10]. Insulin-induced hypoglycemia inhibits pulsatile LH secretion in rats [11,12], sheep [13,14], a n d m o n k e y s [ 1 5 , 1 6 ] . P h a r m a c o l o g i c a l glucoprivation with the administration of 2-deoxy-D-g lucose (2DG), a competitive inhibitor of intracellular glucose oxidation, suppresses pulsatile LH secretion in rats [17,18] and sheep [19].…”