Augmentation of the sterilizing effect of neonatal androgenization with tropolone, a catechol-O-methyltransferase inhibitor, in female rats.
The influence of tropolone, a catechol-O-methyltransferase (COMT) inhibitor, on the sterilizing effect of neonatal testosterone propionate (TP) has been studied in Wistar female rats. Tropolone-induced changes in COMT activity and noradrenaline (NA) and dopamine (DA) contents in the hypothalamus have been evaluated. Inhibition of COMT activity was maximal 3 h after a single injection of 0.6 mg tropolone on postnatal day 5. An increase in DA level was observed 6 h after drug injection, whereas the NA content was elevated 24 h after tropolone administration. A sexual dimorphism in hypothalamic NA content in rats was found on postnatal day 10: it was higher in males than in females. The rise of catecholamines in the hypothalamus of 10-day-old female rats induced by COMT inhibition with tropolone (0.3 mg on postnatal days 5 and 7) was unable to masculinize developing neuroendocrine regions responsible for sexual cyclicity. At the same time, combined administration of tropolone (0.1 mg daily on postnatal days 4-10) and TP (0.025 mg on day 4) enhanced the sterilizing effect of the androgen. An anovulatory sterility appeared in all experimental animals. It is suggested that a cooperative interaction occurs between catecholamines and sex steroids as determinants of brain sexual differentiation.
Reznikov
A G
AG
Research Institute of Endocrinology and Metabolism, Kiev, USSR.
Nosenko
N D
ND
Tarasenko
L V
LV
D000818:Animals; D000831:Animals, Newborn; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000378:metabolism; D004357:Drug Synergism; D004971:Estrus / Q000187:drug effects; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007247:Infertility, Female / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*; D014334:Tropolone / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects
D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D013739:Testosterone; D014334:Tropolone