Copulatory behavior and hypothalamic estrogen and progestin receptors in chronically insulin-deficient female rats

The effects of relatively short- or long-term diabetes on sexual receptivity and proceptivity and on hypothalamic estrogen and progestin receptors were examined in rats fed regular chow or high fat diet. Ovariectomized, streptozotocin-induced chronically insulin deficient and normal rats received sequential treatments with 2 μg estradiol benzoate (EB) and 1 mg progesterone (P) 10 days following the induction of diabetes and were tested for lordosis and soliciting behaviors. Nondiabetic rats fed either diet displayed significantly higher lordosis and solicitation behaviors than chow-fed diabetics, and fat-fed diabetic animals displayed behavior levels intermediate to those of nondiabetic and chow-fed rats. Ten days after the induction of diabetes, the levels of hypothalamic estrogen receptors of chow-fed diabetics were significantly lower than nondiabetics with the fat-fed diabetic group showing intermediate levels. However, 70 days after streptozotocin treatment diabetic rats had significantly lower estrogen receptors than nondiabetics regardless of the diet. Treatment of long-term (70 days) diabetic rats with 1–2 U of U-100 Lente insulin for 24 hr or 7 days was ineffective in restoring the hypothalamic estrogen receptor concentrations to those of nondiabetics. Three weeks following induction of diabetes, induction of cytoplasmic progestin receptors by EB treatment was significantly impaired in diabetic animals fed either chow or high fat diet. Although the reproductive dysfunctions present in short-term diabetic female rats may be due in part to chronic fuel deprivation, it appears that the long-term maintenance of cytosol estrogen receptor level is dependent on other actions of insulin. Furthermore, restoration of hypothalamic estrogen receptors in long-term diabetic rats may require either longer than 7 days of insulin therapy or another mode of treatment (e.g., sex hormones). The behavioral improvement of diabetic animals on HF diet could be accounted for by mechanisms other than enhancement of EB-induced cytoplasmic progestin receptors.