Summary. The effects of long-and short-term streptozotocininduced 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 streptozotoein-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.Key words: Streptozotocin, diabetes mellitus, fertility, luteinizing hormone, luteinizing hormone -releasing hormone, steroid feedback, body weight.It is well known that diabetic patients show an increased incidence of infertility [1], but the mechanisms by which diabetes mellitus impairs reproductive functions are poorly understood. Drug-induced diabetes mellitus in the female rat has frequently been used as an experimental model to investigate the causes of this association, since both alloxan-and streptozotocin-induced diabetes result in ovulatory failure [2,3]. A reduced sensitivity of the pituitary gonadotrophs to luteinizing hormone-releasing hormone (LHRH) has been observed in diabetic rats [4] but this could be attributed to an impairment of LHRH secretion since the releasing hormone regulates its own pituitary receptors [5]. Indeed, the available evidence strongly indicates that diabetes inhibits the hypothalamic regulation of gonadotrophin secretion, and this could involve a failure in the feedback action of gonadal steroids. However, a direct effect of diabetes on the pituitary gland or on the ovary cannot be excluded.The majority of studies have been carried out on the immature animal in which ovulation is stimulated by the administration of pregnant mare's serum gonadotrophin. This particular animal model has some disadvantages since it precludes the c...

Scatchard analysis of specific guanosine-diphosphate-([3H]GDP-) binding to rat brown-adipose-tissue mitochondria revealed two distinct binding sites with apparent dissociation constants (Kd) of approximately 0.05 and 2.0 microM. Binding to both sites was insensitive to atractyloside. Reducing the pH of the binding medium from 7.1 to 6.6 caused marked reductions in the Kd of both sites, but at pH 7.6, the dissociation constants were increased about 3-fold. Acute treatment of rats with noradrenaline, 1 h before sacrifice, increased the maximum number of binding sites (Bmax, pmol/mg mitochondrial protein) of both sites and also increased the dissociation constants. The Bmax of the lower-affinity site was elevated in rats exposed to 5 degrees C or fed a palatable cafeteria diet for 10 d, compared to control animals, with the greater changes occurring in the cold-adapted group. The high-affinity site was unaltered by cold adaptation or cafeteria feeding. These results indicate the presence of two distinct nucleotide-binding sites in brown-fat mitochondria, both of which may be involved in thermogenesis.

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