DEPRESSED LUTEINIZING-HORMONE RESPONSE TO ESTRADIOL IN-VIVO AND GONADOTROPIN-RELEASING-HORMONE IN-VITRO IN EXPERIMENTALLY DIABETIC SWINE

The influence of the acute withdrawal of insulin therapy in streptozoc in-diabetic female swine was examined for changes in 1) the in vivo pu lsatile secretion of luteinizing hormone (LH), 2) the preovulatory-lik e gonadotropin patterns after exogenous estradiol, and 3) the in vitro LH secretion by cultured pituitary cells. In Experiment 1, ovariectom ized diabetic pigs (n = 4) were maintained with insulin therapy until 4 d before estradiol benzoate (EB; 7 mu g/kg body weight; subcutaneous ) was administered. Four normal ovariectomized pigs, matched for age a nd weight, served as controls. The diabetic state was confirmed by the measurement of glucose and insulin concentrations during a glucose to lerance test. Pulsatile LH secretion was not influenced by experimenta l diabetes mellitus. However, the expected surge in LH was not induced by EB in diabetic gilts. In contrast, three of four normal gilts had a preovulatory-type surge in LH. Concentrations of follicle-stimulatin g hormone in serum were not affected by diabetes mellitus. Estradiol c oncentrations in serum after EB were influenced by diabetes mellitus ( treatment by time interaction; P < 0.001). In individual estradiol pro files, maximum concentrations were similar (104 +/- 10.4 and 91 +/- 12 .0 ng/ml for normal and diabetic pigs, respectively), but the interval to maximum concentration was delayed in diabetic pigs (27.5 vs. 9.0 h ; SE = 3.0; P < 0.05). However, the duration of standing estrus (2.2 /- .3 d) and the interval from EB to estrus (3.6 +/- 0.3 d) were not i nfluenced by diabetes mellitus. In Experiment 2, LH secretion by cultu red cells and residual cellular LH content were greater in the pituita ries of normal than diabetic pigs (P < 0.05), and only cells from norm al pigs responded to gonadotropin-releasing hormone (GnRH), with incre ased production of LH (P < 0.05). In conclusion, diabetes mellitus did not affect pulsatile LH secretion but did lower the ability of exogen ous estradiol to stimulate a surge in vivo and of GnRH to increase LH in vitro, suggesting that the pituitary response to estradiol and GnRH is more severely affected by diabetes than is the GnRH pulse generato r.