Feedback effects of steroids and gonadotrophin control in adult rats with streptozotocin-induced diabetes mellitus.

The effects of long-and short-term streptozotocin-induced diabetes mellitus on the control of gonadotrophin secretion have been investigated in adult intact rats. A high dose of streptozotocin (80 mg/kg), administered intraperitoneally 3 days before experimentation, inhibited ovulation and reduced the pituitary luteinizing hormone response to luteinizing hormone releasing hormone in proestrous rats. A lower dose (40 mg/kg) did not inhibit ovulation but abolished the luteinizing hormone releasing hormone-priming effect on the pituitary which normally occurs on proestrus, prior to ovulation. Oestrous cyclicity was lost when diabetes was induced for 14 or 56 days, but there was no effect on pituitary responsiveness to luteinizing hormone-releasing hormone compared with control animals. Similar observations were made with rats placed on a food-restricted diet. In all experiments there was no difference between diabetic and control animals in the pituitary luteinizing hormone content, the hypothalamic content of luteinizing hormone-releasing hormone or the ovarian weights. Ovariectomized rats treated with streptozotocin (40 mg/kg) were used to investigate the effects of diabetes on steroid feedback mechanisms. There was an attenuated luteinizing hormone response to ovariectomy in diabetic compared with control animals, and an impaired positive feedback effect of progesterone in oestrogen-primed animals. The results show that streptozotocin-induced diabetes mellitus inhibits feedback action of gonadal steroids and this could account for both the loss of oestrous cyclicity and the reduced pituitary sensitivity to luteinizing hormone-releasing hormone.