Hypoglycemia-induced inhibition of LH and stimulation of ACTH secretion in the rhesus monkey is blocked by alprazolam.

Abstract

Insulin-induced hypoglycemia inhibits luteinizing hormone (LH) secretion and has been used as a model to study stress-induced inhibition of reproductive function. Endogenous opioid peptides have been implicated in mediating the inhibitory effect of hypoglycemia on LH secretion in sheep and rat. The objective of the present study was to determine if corticotropin-releasing hormone (CRH) and endogenous opiates are involved in the LH response to hypoglycemia in the nonhuman primate. Blood samples were collected at 15-min intervals for 6 h from ovariectomized rhesus monkeys (n = 6). Hypoglycemia was induced by injecting insulin 1 h after initiating blood collection. Animals were pretreated 15 min prior to insulin with either saline (n = 6), naloxone, a nonselective opiate receptor antagonist (n = 4), or alprazolam (n = 6), a potent benzodiazepine which has been shown to inhibit CRH. The LH, glucose, adrenocorticotropin (ACTH), and cortisol responses to insulin were determined. Insulin-induced hypoglycemia significantly inhibited LH secretion and increased ACTH and cortisol concentrations. Alprazolam prevented hypoglycemia-induced inhibition of LH independent of an effect on glucose concentrations. The mean (+/- SEM) LH pulse interval in response to hypoglycemia was decreased in the alprazolam pretreated group compared to the saline pretreated group (77.4 +/- 6.0 vs. 130.0 +/- 18.4 min), while LH pulse amplitude and mean LH levels were significantly increased (56.2 +/- 7.1 vs. 28.3 +/- 5.5 ng/ml, and 105.6 +/- 14.4 vs. 60.9 +/- 12.1 ng/ml respectively). In contrast, naloxone did not prevent hypoglycemia-induced LH inhibition. The mean LH pulse interval, LH pulse amplitude, and LH concentration in the naloxone pretreated monkeys were 152.1 +/- 33.4 min, 37.1 +/- 8.9 ng/ml, and 63.7 +/- 9.1 ng/ml respectively. Alprazolam pretreatment also markedly attenuated the ACTH response to hypoglycemia whereas the cortisol response was only moderately affected. We conclude that insulin-induced hypoglycemia in the monkey inhibits LH secretion through a mechanism involving CRH but not endogenous opiates.