Altered hypothalamic-pituitary function in the adult female rat with streptozotocin-induced diabetes

Abstract

Infertility associated with anovulation and loss of regular oestrous cyclicity is a consequence of diabetes mellitus in the rat. In an attempt to define loci of altered function, studies were undertaken to examine various aspects of hypothalamic-pituitary function in rats treated with streptozotocin. Medial basal hypothalamic fragments from adult female diabetic rats contained the same amount of gonadotrophin-releasing hormone but, with depolarization, released slightly but insignificantly (p>0.05) more than did those from control animals. Furthermore, release of luteinizing hormone from pituitaries exposed to hypothalamic gonadotrophin-releasing hormone was not altered by diabetes. Removal of the negative feedback effect of gonadal steroids upon the hypothalamic-pituitary axis produced an increase in luteinizing hormone and follicle stimulating hormone concentrations in the serum of normal rats within 6h (p<0.05), whereas 24h were required for similar increases in diabetic rats. However, the same concentrations of gonadotrophins were found in diabetic and control animals 120h after ovariectomy. The inhibitory action of oestradiol benzoate on the secretion of gonadotrophins was more pronounced in ovariectomized diabetic than in control rats. A 74% depression in serum luteinizing hormone (p<0.01) was produced by 0.5 μg oestradiol benzoate per day in diabetic rats, while 5 μg was required in control animals. Similar reductions in follicle stimulating hormone concentrations (50%, p<0.05) were obtained by injecting 5 μg of the oestrogen into diabetic or 50 μg into control rats. Increases in serum prolactin were greater in the control animals however. Although pituitary weights were consistently lower in oestrogen-treated diabetic than in control animals, the luteinizing hormone, follicle stimulating hormone and prolactin contents, on the basis of wet weight of gland, were not different (p>0.05). The positive feedback action of progesterone on release of luteinizing hormone that had been suppressed with oestradiol benzoate was delayed by 3 h and reduced by more than 50% in diabetic compared to control animals (p<0.01). Release of follicle stimulating hormone was also delayed and reduced in the diabetic rats. While several indices of hypothalamic-pituitary function were not greatly altered by streptozotocin-induced diabetes, the enhanced negative and reduced positive-feedback effects of steroids could be responsible for attenuated gonadotrophin surges and loss of cyclicity in diabetic female rats. © 1985 Springer-Verlag.