Reduced hypothalamic serotonin synthesis and serum luteinizing hormone levels in streptozotocin-diabetic male rats

Infertility is a common sequela to experimentally-induced diabetes mellitus in the male rat as well as to diabetes in the human male. This has been attributed both to alterations in hypothalamo-pituitary and pituitary-testicular activity. In view of the role of serotonin in the hypothalamic regulation of luteinizing hormone secretion, we determined the effects of streptozotocin-induced diabetes on hypothalamic serotonin synthesis relative to circulating levels of luteinizing hormone, follicle-stimulating hormone and prolactin in these animals. Half of a group of adult male Sprague-Dawley rats were injected intraperitoneally with 16 mg·kg^-1 of streptozotocin. The other half were injected with vehicle only. The diabetic group was hyperglycemic throughout the study period (488.7±21.2 mg·dl^-1 in diabetic rats vs. 125.1±39.3 mg·dl^-1 in control rats). A third group of rats served as semi-starved controls, weight-matched by total calorie restriction diet to diabetic rats. All of the rats were injected intraperitoneally with 200 mg·kg^-1 NSD-1015 30 min prior to sacrifice. Accumulation of 5-hydroxytryptophan in various hypothalamic areas was then assayed by liquid chromatography with electrochemical detection as a relative index for rate of serotonin synthesis. Serum radioimmunoassayable luteinizing hormone, follicle-stimulating hormone and prolactin were also assayed in these animals. Our results show a 50% decrease in serotonin synthesis in the preoptic area-anterior hypothalamus and mediobasal hypothalamus-median eminence 16 weeks after streptozotocin treatment. We also found that serotonin synthesis was inhibited 4 weeks after streptozotocin treatment in the preoptic area-anterior hypothalamus, but not in the mediobasal hypothalamus-median eminence, indicating region-specificity in the early hypothalamic response to streptozotocin-induced diabetes. Serum luteinizing hormone levels were decreased both 4 and 16 weeks after streptozotocin treatment. No changes either in hypothalamic serotonin synthesis or serum luteinizing hormone levels were observed 1 week after streptozotocin treatment. Serum follicle-stimulating hormone and prolactin levels remained unaffected by streptozotocin treatment throughout the study period. The differential effect of diabetes on the gonadotropins may represent further evidence for the hypothesis of differential regulatory mechanisms governing the secretion of these two hormones and further emphasizes the pathophysiological specificity (i.e., not a generalized metabolic disturbance effect) of diabetes-induced male reproductive neuroendocrinopathy. Our study suggests, at least in part, an explanation for such pathological interaction, namely, diabetic inhibition of a region-specific neurotransmitter system integral to hypothalamic regulation of luteinizing hormone secretion.