HYPOGLYCEMIA-INDUCED INHIBITION OF LH AND STIMULATION OF ACTH-SECRETION IN THE RHESUS-MONKEY IS BLOCKED BY ALPRAZOLAM

Insulin-induced hypoglycemia inhibits luteinizing hormone (LH) secreti on 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 invo lved in the LH response to hypoglycemia in the nonhuman primate. Blood samples were collected at 15-min intervals for 6 h from ovariectomize d rhesus monkeys (n = 6). Hypoglycemia was induced by injecting insuli n 1 h after initiating blood collection. Animals were pretreated 15 mi n prior to insulin with either saline (n = 6), naloxone, a nonselectiv e opiate receptor antagonist (n = 4), or alprazolam (n = 6), a potent benzodiazepine which has been shown to inhibit CRH. The LH, glucose, a drenocorticotropin (ACTH), and cortisol responses to insulin were dete rmined. Insulin-induced hypoglycemia significantly inhibited LH secret ion and increased ACTH and cortisol concentrations. Alprazolam prevent ed hypoglycemia-induced inhibition of LH independent of an effect on g lucose concentrations. The mean (+/- SEM) LH pulse interval in respons e to hypoglycemia was decreased in the alprazolam pretreated group com pared 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 i ncreased (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 preve nt hypoglycemia-induced LH inhibition. The mean LH pulse interval, LH pulse amplitude, and LH concentration in the naloxone pretreated monke ys 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 AC TH response to hypoglycemia whereas the cortisol response was only mod erately affected. We conclude that insulin-induced hypoglycemia in the monkey inhibits LH secretion through a mechanism involving CRH but no t endogenous opiates.