[Effects of aromatase inhibitor on sexual differentiation of SDN-POA in rats].
The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats is larger than that of females, the difference being caused by the perinatal effect of estrogen converted from androgen. To investigate the role of estrogen formation in the SDN-POA during the critical period of this sexual differentiation, CGS16949A (0.5 mg/kg, sc) was injected into the mothers in the late gestational age(F) or into neonates for 14 days from birth(N). Animals were sacrificed on the 20th. day of gestation and 7 days after birth, and fetal and neonatal brain aromatase activities (AA) as well as serum levels of testosterone(T) and corticosterone(B) were measured. On the 30th day after birth, the offspring of treated mothers and neonatally treated rats were sacrificed and the cross-sectional areas of the SDN-POA were evaluated by image processor NEXUS 6800. In group F, CGS16949A markedly suppressed brain AA in vitro (fetal hypothalamus: IC50 1.4nM) and in vivo in both the hypothalamus and amygdala. However, the levels of T and B did not show any significant change in group F. The same depression of AA was also observed in group N on the 7th day after birth. In CGS-treated males in groups F and N, the SDN-POA area markedly decreased to that of control females. The area in males in group F was not significantly different from that in females. These results suggest that estrogen converted from androgen plays a dominant role in the development of sexual dimorphism of the SDN-POA, and that the brain AA in the pre- and postnatal period is important in this process.
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Department of Obstetrics and Gynecology, Teikyo University, School of Medicine, Tokyo.
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D001921:Brain / Q000201:enzymology; D003345:Corticosterone / Q000097:blood; D017316:Fadrozole / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011301:Preoptic Area / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012733:Sex Differentiation / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D047072:Aromatase Inhibitors; D013739:Testosterone; D001141:Aromatase; D017316:Fadrozole; D003345:Corticosterone