Endocrine Effects of Brain Serotonin Depletion by 5,6-Dihydroxytryptamine in Prepuberal Male Rats

Abstract

The effects of selective degeneration of brainserotoninergic nerve terminals by 5,6-dihydroxytryptamine (5,6-DHT) injected intraventricularly in prepuberal male rats were studied in 2 experiments. In both experiments, male Sprague-Dawley rats were injected in a lateral ventricle of the brain at 21 and 23 days of age with either 5,6-DHT or vehicle, and autopsied 1,2 and 4 weeks after the 1st injection. Controls were either pair-fed or fed ad lib. In the first experiment the effects of 5,6-DHT on body and organ growth and pituitary levels of radioimmunoassayable growth hormone (GH) were studied. In the second experiment the effects of 5,6-DHT on plasma and pituitary levels of radioimmunoassayable follicle-stimulating hormone (FSH) were studied. Histological examinations of the testes obtained at 4 weeks were performed. Experimental animals on the whole ate 41.8 % less food than controls fed ad lib. The analysis of variance showed that experimental animals, when compared with pair-fed controls, had significantly lower brain 5-HT levels (as measured by spectrophotofluoro-metry) at 1 and 2 weeks, significantly lower body weights at 1 week, and significantly smaller tails at 1 and 2 weeks after the first injection. Brain weights of experimental rats were significantly lower than those of controls fed ad lib. at 2 and 4 weeks; those of pair-fed animals, although lower at 2 weeks, were not significantly different from brain weights of controls fed ad lib. at 4 weeks. At 4 weeks, testes weights (corrected for body weights) were significantly lower in experimental rats than in controls fed ad lib. At 2 weeks, both the experimental and the pair-fed group had pituitary GH levels (corrected for body weights) lower than those of the group fed ad lib. Plasma FSH levels were undetectable at 1 week both in experimental and pair-fed animals. Pituitary FSH concentration was significantly reduced at 2 weeks and significantly increased at 4 weeks in the experimental rats when compared with the controls fed ad lib. Histological examination of the testes showed that controls fed ad lib. and pair-fed had reached full spermatogenesis at 4 weeks after the 1st injection (51 days of age); spermatogenesis of experimental animals was usually blocked at the stage of pachytene spermatocytes. In conclusion, depletion of brain 5-HT inhibited body and brain growth and sexual maturation partly through the ensuing anorexia and malnutrition, but possibly also through a specific decrease in synthesis and/or secretion of GH and FSH.