[The neuroendocrine effects of neonatal exposure to an inhibitor of catechol-o-methyltransferase and of sex steroids]

Abstract

The role of catechol-o-methyltransferase (COMT) in functional interrelationship between testosterone (T), catechol estrogens (CE) and catecholamines (CA) during cerebral sex differentiation (CSD) was investigated in experiments on Wistar rats. Sex dimorphism in the level of CA in the rat hypothalamus was revealed on the 10th day of life. Noradrenaline concentration in male rats was significantly higher than in the female rats (p less than 0.05). It was shown that isolated CA accumulation in the hypothalamus of 10-day female rats by means of direct suppression of COMT with tropolon (300 micrograms on the 5th and 7th days of life) was insufficient for masculinization of sex cycling regulation centers. At the same time tropolon administered in a dose of 100 micrograms on the 4th-10th days of life enhanced the sterilizing effect of T administered in a dose of 25 micrograms on the 4th day of life. The development of anovulatory sterility (AS) was observed in 100% of cases. The neonatal effect of 2-hydroxyestradiol-17 beta (2-OH-E2 50 micrograms on the 5th day of life) and tropolon (300 micrograms on the 5th and 7th days of life) was ineffective with relation to AS induction indicating the absence of the inductor role of 2-OH-E2 in CSD. A conclusion is that CSD is a result of combined action of androgens, their metabolites (4-hydroxylated CE isomers) and COMT-mediated CA.