EFFECT OF GROWTH-HORMONE ON RAT HEPATIC CYTOCHROME-P-450F MESSENGER-RNA - A NEW MODE OF REGULATION

Growth hormone (GH) is known to be involved in the control of rat hepatic drug and steroid metabolism through its action on cytochrome P-450s. To examine the role of GH in the regulation of cytochrome P-450f (P-450f), a full-length cDNA clone corresponding to P-450f was isolated and the 3'-non-coding region was utilized for Northern and slot-blot analyses. P-450f mRNA levels were low in neonates, increased after age 4 weeks in male and female rats, and were approximately 3 times higher in the liver of adult female rats than male rats. Hypophysectomy caused a significant decrease in P-450f mRNA levels in male and female rats. Intermittent injection with human growth hormone (hGH) to mimic the male secretory pattern of GH caused a 9-fold increase in P-450f mRNA in hypophysectomized male rats to levels near male control levels, whereas continuous administration of hGH to mimic the female secretory pattern caused a greater increase in P-450f mRNA levels in male and female hypophysectomized rats (25-fold and 9-fold respectively) to levels nearer female control levels. The responses of the other GH-stimulated P-450s, P-450-male and P-450-female, to the different modes of hGH treatment were different from that of P-450f. Since sex hormones are known to affect the regulation of other P-450s, the effect of sex hormones on P-450f mRNA was studied. Ovariectomy caused a 2.4-fold reduction in P-450f mRNA which was partially reversed by estradiol treatment. These results demonstrate a role for GH and sex steroids in the regulation of P-450f mRNA. The mode of regulation of P-450f mRNA by GH was distinct from other known P-450s. © 1990.