INFLUENCE OF DIABETES ON THE GONADOTROPIN-RESPONSE TO THE NEGATIVE FEEDBACK EFFECT OF TESTOSTERONE AND HYPOTHALAMIC NEUROTRANSMITTER TURNOVER IN ADULT MALE-RATS

The influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone (T) and hypothalamic neurotransmitter turnover rates in adult male rats was evaluated. Adult male Sprague-Dawley rats were made diabetic by an intraperitoneal injection of streptozotocin (STZ; 5 mg/100 g body weight) in citrate buffer. Vehicle-injected rats served as controls. On day 9, all rats were bilaterally castrated and treated subcutaneously on alternate days with either peanut oil or T propionate (TP) in peanut oil (100-mu-g/rat). Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and T concentrations were measured by specific radioimmunoassays from blood samples collected on day 1 (before castration) and 2, 4, 6, and 7 days after castration. On day 7 after castration (day 15 after vehicle or STZ treatment), 1 h before autopsy, the rats were injected intraperitoneally with saline or a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (25 mg/100 g BW), for the measurements of norepinephrine (NE) and dopamine turnover in median eminence and medial basal hypothalamus (MBH). Circulating FSH, LH, PRL, and T levels were significantly lower (FSH and T: p < 0.001; LH and PRL: p < 0.05) in gonad-intact rats treated with STZ than in vehicle-injected animals. The castration-induced increase in plasma LH levels was attenuated in diabetic rats. The suppressive effect of T on LH secretion was significantly greater (p < 0.001) in STZ-treated rats relative to TP-treated nondiabetic controls. Castration in both diabetic and nondiabetic rats increased (p < 0.001) FSH secretion, but these increases were not different until day 6 after castration, when plasma FSH levels in control rats significantly increased (p < 0.01), than in diabetic animals. In STZ-treated rats, the suppressive effect of TP on plasma FSH levels was significantly increased. The NE turnover rates in median eminence and MBH were significantly lower (p < 0.001) in castrated diabetic rats than in castrated controls. The MBH NE turnover was reduced after TP treatment in both subgroups, but the relative decline was much greater (p < 0.01) in diabetic rats. These results clearly indicate that induction of diabetes by STZ treatment reduces gonadotropin and PRL secretion and increases the sensitivity of the hypothalamic-pituitary axis to the negative feedback effect of T on gonadotropin secretion. The effect of diabetes on gonadotropin secretion in the adult male rat is probably due to the suppression of noradrenergic neuronal activity of the hypothalamus.