Evidence that physiologic levels of circulating estrogens and neonatal sex-imprinting modify postpubertal hepatic microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.
Intact, but sham-operated female rats had 2- to 3-fold higher levels of hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity than their male counterparts (15--21.5 vs. 6.7--8.7 nmol mevalonate/mg protein per h). The activity of the hepatic enzyme declined to about the same relative degree (40--60%) in male and female rats that were gonadectomized after puberty (53 days of age) and killed 5 weeks later. Implantation of silastic capsules containing 17 beta-estradiol increased the level of hepatic 3-hydroxy-3-methylglutaryl CoA reductase to levels found in sham-operated controls. In rats that were gonadectomized in infancy (12 h old) and killed 7--8 weeks later, the level of enzyme activity was not altered in females, but it was increased from 60--240% in males. Consequently, following neonatal gonadectomy, male-female differences in enzyme activity were no longer apparent. Implantation of silastic capsules containing estradiol in neonatally gonadectomized rats resulted in a doubling of enzyme activity in both males and females. Ovariectomy reduced plasma estrogen levels, but implantation of estradiol in gonadectomized males and females increased the hormone level to that found in sham-operated females. Thus, the results strongly suggest a role for physiologic levels of estrogen as a positive effector of 3-hydroxy-3-methylglutaryl CoA reductase activity. Neonatal sex imprinting also appears to modulate the enzyme activity since sex-mediated differences are effaced by gonadectomy in infancy, but not by gonadectomy following puberty.
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D002369:Castration; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000097:blood*; D004971:Estrus; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007173:Imprinting, Psychological; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D012737:Sex Factors; D012741:Sexual Maturation; D013739:Testosterone / Q000494:pharmacology
D004967:Estrogens; D013739:Testosterone; D004958:Estradiol; D006903:Hydroxymethylglutaryl CoA Reductases