The ability of insulin replacement to reverse the adverse effects of streptozocin-induced diabetes (STZD) on neuroendocrine and sexual function was tested in adult male rats. Rats were injected with STZ (50 mg/kg) or vehicle and then either started immediately on insulin (continuous) or allowed to remain untreated for 4 wk before insulin replacement was started (delayed). Replacement consisted of 5 IU/kg of insulin injected just before the lights were turned off and 2 IU/kg of insulin injected within 1 h of the lights being turned on. Copulatory behavior was tested 2, 4, 5, and 6 wk after induction of diabetes. Forty-five days after STZ administration, rats were killed for measurement of plasma hormone levels and hypothalamic catecholamine turnover and serotonin content. The STZ-D rats showed significant deficits in mount, intromission, and ejaculatory behaviors that were prevented by continuous insulin replacement. Delayed insulin replacement reversed the deficits in mount and intromission behaviors but not ejaculatory behavior. Plasma luteinizing hormone levels were unaffected by STZ or insulin treatment, but plasma testosterone and prolactin levels were both reduced in the diabetic animals. Continuous or delayed insulin replacement normalized both testosterone and prolactin levels. Median eminence, medial basal hypothalamus, anterior hypothalamus, and olfactory bulb rates of norepinephrine turnover were all reduced after STZ administration. Delayed insulin replacement restored norepinephrine turnover in all brain regions, whereas continuous insulin replacement enhanced norepinephrine turnover in the anterior hypothalamus and olfactory bulb but only partially blocked the effects of STZ in the median eminence and medial basal hypothalamus. STZ induced decreases in dopamine turnover in the medial basal hypothalamus and olfactory bulb, and these changes could not be prevented or reversed by insulin replacement. These results demonstrate that many but not all of the adverse effects of STZ-D on copulatory behavior and neuroendocrine function can be reversed by insulin replacement.

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