Reproductive endocrinopathy in acute streptozotocin-induced diabetic male rats. Studies on LHRH.

Streptozotocin-(STZ) treated diabetic male rats have significant reproductive endocrinopathy. To determine the functional responsiveness of luteinizing hormone-releasing hormone (LHRH) neurons in STZ-treated diabetic male rats, stimulated LHRH release was assessed using hypothalami from short-term STZ-treated, STZ-treated insulin-replaced, and control male rats. LHRH release from control, STZ-treated, and STZ-treated, insulin-replaced explants in response to an initial and second 30-min pulse of phenylephrine were not different. A terminal pulse, containing 45 mM KCl, a general secretogogue, also revealed no differences between groups in stimulated LHRH release. Glucose and testosterone levels in the controls and the diabetic rats were significantly different. Cell counts on serial brain sections processed for LHRH immunohistochemistry suggested that the number of LHRH neurons in the preoptic area (POA) and septal areas were not different between control and STZ-treated rats. Thus, the short-term STZ-treated rats of this study were diabetic, and they displayed associated endocrinopathy; however, explants obtained from control and STZ-treated rats exhibited a typical LHRH responsiveness to both phenylephrine and KCl, and appeared similar in LHRH neuron number. Therefore, these findings suggest that reproductive endocrinopathy accompanying short-term STZ-induced diabetes in male rats does not result from deficiency in LHRH neurons per se.

Effects of streptozotocin-induced diabetes on neuroendocrine responses to ovariectomy and estrogen replacement in female rats.

The effects of streptozotocin-induced (STZ) diabetes on the negative feedback regulation of LH and FSH were evaluated in adult female rats. Rats were injected with STZ (50 mg/kg) or vehicle and ovariectomized 10 days later. Estrogen (EB; 100 micrograms/kg) or oil injections were given on alternate days, starting on the day of ovariectomy. Blood samples for LH, FSH and PRL assay were taken on days 10, 13, 15 and 17. The rats were decapitated on day 17. One hour prior to sacrifice, one half of the animals were injected with alpha-methyl-p-tyrosine for determination of catecholamine turnover rates. Pituitaries were incubated to determine basal secretion rates. Rats treated with STZ exhibited the expected weight loss and elevation of plasma glucose levels. At the time of ovariectomy, FSH, but not LH or PRL, was depressed in the diabetic rats. The postovariectomy rise in LH and FSH was severely attenuated in the diabetic rats. EB treatment was more effective in lowering LH and FSH levels in the diabetic as compared to the control rats. Median eminence (ME) norepinephrine (NE) and dopamine (DA) turnover was higher in the oil-treated diabetic rats than oil-treated controls. EB also caused a greater decrease in ME NE and DA turnover in the diabetic rats. EB was more effective in decreasing in vitro LH secretion and increasing in vitro PRL secretion from pituitaries of control as compared to STZ-treated animals. These results demonstrated that STZ-induced diabetes leads to an attenuation of LH and FSH release after ovariectomy and potentiates the negative feedback effects of EB.(ABSTRACT TRUNCATED AT 250 WORDS)

Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat.

The effects of streptozotocin-induced (STZ) diabetes on the release of gonadotropins was studied in female rats. In the first experiment, rats were ovariectomized and 2 days later were injected with STZ. Three weeks later rats were treated with estrogen and progesterone and blood samples were taken via intraatrial cannulae for luteinizing hormone (LH) assay. Afternoon surges of LH were seen in 4/5 control but 0/8 STZ rats. Pituitary responses to LH-releasing hormone in vitro did not differ. In the 2nd experiment, ovariectomized estrogen-primed rats were killed prior to and during a progesterone-induced LH surge. As in Experiment 1, STZ-treatment inhibited the LH surge but did not effect the afternoon rise in median eminence norepinephrine turnover which has previously been shown to be important in stimulating LH release. Turnover of norepinephrine in the anterior hypothalamus was depressed in the diabetic rats both prior to and during the expected time of the LH surge. Dopamine turnover was depressed in all three brain regions studied. It can be concluded that the positive feedback control of LH release is severely attenuated in diabetic rats but the mechanism explaining the loss is not clear. Diabetes-induced alterations in hypothalamic catecholamine metabolism may be involved but further work is needed to more carefully define these relationships.

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 micrograms/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 measurement 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 less than 0.001; LH and PRL: p less than 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 less than 0.001) in STZ-treated rats relative to TP-treated nondiabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)