Growth hormone regulation and developmental expression of rat hepatic CYP3A18, CYP3A9, and CYP3A2

The present study investigated the role of growth hormone (GH) in hepatic C YP3A18 and CYP3A9 expression in prepubertal and adult male rats. For compar ison, the effects of GH on CYP3A2 expression were also measured. Initial ex periments demonstrated that CYP3A18 mRNA levels were greater during puberty and adulthood than during the prepubertal period, CYP3A9 mRNA was not expr essed until puberty and its expression increased in adulthood, and CYP3A2 m RNA. levels were relatively constant from prepuberty to adult life. Hypophy sectomy, which results in the loss of multiple pituitary factors including GH, increased CYP3A2 and CYP3A18 mRNA expression 3- to 4-fold, but it did n ot affect CYP3A9 mRNA levels or CYP3A-mediated testosterone 2 beta- or 6 be ta-hydroxylase activity in adult rats. GH administered as twice daily s.c i njections (0.12 mu g/g body weight) to hypophysectomized or intact adult ra ts did not affect CYP3A18 or CYP3A9 mRNA expression. The same treatment dec reased CYP3A2 mRNA and protein and testosterone 2 beta-and 6 beta-hydroxyla se activity levels in intact but not hypophysectomized rats. However, in in tact prepubertal rats, intermittent GH administration decreased CYP3A18 and CYP3A2 mRNA levels, but a higher dosage (3.6 mu g/g) was required to suppr ess CYP3A2. Overall, the present study demonstrated that: (a) the constitut ive expression of CYP3A18, CYP3A9, and CYP3A2 does not require the presence of GH, (b) CYP3A18 is more sensitive than CYP3A9 to GH modulation in adult rats; and (c) CYP3A2 is less sensitive to the suppressive influence of GH during the prepubertal period than during adult life. (C) 2000 Elsevier Sci ence Inc.