Role of growth hormone in modulating the constitutive and phenobarbital-induced levels of two P-450_6β (testosterone -6βhydroxylase) mRNAs in rat livers

The role of growth hormone in the expression of two forms of hepatic cytochrome P-450(P-450), P-450_{6β8β-1(6β-3)}, and P-450_6β-4, was investigated using RNA blots. The level of P-450_6β-1(6β-3) mRNA was twenty times higher than that of P-450_6β-4 mRNA in untreated male rat livers. The levels of P-450_6β-1(6β-3) and P-4506_β-4 mRNAs were increased two fold and three fold, respectively, by hypophysectomy of adult male rats. By intermittent injection of human growth hormone (hGH) into hypophysectomized male rats, both mRNAs were decreased to the level of normal rats, and almost disappeared after continuous infusion of hGH. In female rats, these two mRNAs were not detected, but were increased remarkably by hypophysectomy. The increases in these mRNAs were almost abolished after continuous infusion of hGH in hypophysectomized female rats. The effect of hGH on PB-mediated induction of P-450_6β-1(6β-3) and P-450_6β-4 mRNAs was also examined. The PB-mediated increases in P-450_6β-(6β-3) and P-450_6β-4 mRNAs were higher in hypophysectomized male rats (2.5-fold and 10.9-fold, respectively) than in normal male rats (1.5-fold and 5.2-fold, respectively). Thus, the levels of P-450_6β-1(6β-3 and P-450_6β-4 mRNAs were 4.1-fold and 7.3-fold, respectively, higher in PB-induced hypophysectomized rats than in normal male rats. Concerning the postnatal developmental profiles, P-450_6β-1(6β-3) mRNA was detectable at neonate and reached a maximal level at around 17 days of age. The mRNA level, however, abruptly diminished only in female rats at puberty. The change in the mRNA level was largely correlated with that in P-450_6β-1 protein level in normal rats as reported previously (Y. Yamazoe et al (1988) J. Biochem. 104, 785-790). P-450_6β-4 mRNA was detectable in the neonate. The mRNA was detected in livers of male and female rats up to 20 days of age, but was undeteetable in adult female rats. In an experiment using different aged rats, the extent of PB-induced increases in P-450_6β-1(6β-3 and P-450_6β-4 mRNAs was higher in 20-day-old than in 9-week-old male and female rats. These results suggest that pituitary growth hormone suppresses the constitutive and PB-induced levels of expression of two different forms of hepatic testosterone 6β-hydroxylases, P-450_6β-1(6β-3) and P-450^6β-4, mainly at the pretrans-lational level.