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 streptozocin-diabetic female swine was examined for changes in 1) the in vivo pulsatile secretion of luteinizing hormone (LH), 2) the preovulatory-like gonadotropin patterns after exogenous estradiol, and 3) the in vitro LH secretion by cultured pituitary cells. In Experiment 1, ovariectomized diabetic pigs (n = 4) were maintained with insulin therapy until 4 d before estradiol benzoate (EB; 7 μg/kg body weight; subcutaneous) was administered. Four normal ovariectomized pigs, matched for age and weight, served as controls. The diabetic state was confirmed by the measurement of glucose and insulin concentrations during a glucose tolerance test. Pulsatile LH secretion was not influenced by experimental 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-stimulating hormone in serum were not affected by diabetes mellitus. Estradiol concentrations in serum after EB were influenced by diabetes mellitus (treatment by time interaction; P < 0.001). In individual estradiol profiles, 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 influenced by diabetes mellitus. In Experiment 2, LH secretion by cultured cells and residual cellular LH content were greater in the pituitaries of normal than diabetic pigs (P < 0.05), and only cells from normal pigs responded to gonadotropinreleasing hormone (GnRH), with increased production of LH (P < 0.05). In conclusion, diabetes mellitus did not affect pulsatile LH secretion but did lower the ability of exogenous 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 generator.