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 f eedback regulation of LH and FSH were evaluated in adult female rats. Rats were injected with STZ (50 mg/kg) or vehicle and ovariectomized 1 0 days later. Estrogen (EB; 100 mug/kg) or oil injections were given o n alternate days, starting on the day of ovariectomy. Blood samples fo r 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-methylptyrosine for determination of catecholamine turnover rates. Pituitaries were incubated to determ ine basal secretion rates. Rats treated with STZ exhibited the expecte d weight loss and elevation of plasma glucose levels. At the time of o variectomy, FSH, but not LH or PRL, was depressed in the diabetic rats . The postovariectomy rise in LH and FSH was severely attenuated in th e diabetic rats. EB treatment was more effective in lowering LH and FS H levels in the diabetic as compared to the control rats. Median emine nce (ME) norepinephrine (NE) and dopamine (DA) turnover was higher in the oil-treated diabetic rats than oil-treated controls. EB also cause d 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 p otentiates the negative feedback effects of EB. This enhanced feedback effect appears to be mediated through hypothalamic NE metabolism rath er than a direct action on the pituitary gland.