Effects of Hypophysectomy and Growth Hormone Treatment on Sex-Specific Forms of Cytochrome P-450 in Relation to Drug and Steroid Metabolisms in Rat Liver Microsomes

Abstract

Hypophysectomy decreased the content of a male specific cytochrome P-450, P-450-male, in male rats, while it expressed P-450-male and completely depressed a female specific cytochrome P-450, P-450-female, in female rats. Intermittent injections of human growth hormone (GH), which mimic the secretion in males, restored P-450-male in hypophysectomized (Hypox) male rats and partially restored P-450-female in Hypox female rats. Continuous infusion of GH, which mimics the female secretion pattern, into Hypox male rats caused a further decrease in P-450-male content, and it caused the expression of P-450-female. In Hypox female rats, the same treatment depressed P-450-male and expressed P-450-female to the level of an intact female. These results indicate that the diurnal changes in the pattern of serum growth hormone level regulate the expression of P-450-male and P-450-female. The activities of testosterone 2α- and 16α-hydroxylases were closely correlated to P-450-male content with the correlation coefficients (r) of 0.955 and 0.929, respectively. Benzo(a)pyrene hydroxylation was also correlated to P-450-male content (r=0.850). Aminopyrine N-demethylation and propoxycoumarin O-depropylation were correlated to less extents (r=0.692 and r=0.720), while aniline hydroxylation and O-ethylresorufin O-deethylation were not correlated to P-450-male content. These results indicate that testosterone 2α- and 16α-hydroxylations are closely dependent, but the metabolism of a variety of drugs are dependent to different extents on P-450-male in rat liver microsomes.