A SPECIFIC LOSS OF GROWTH-HORMONE ABOLISHED SEX-DEPENDENT EXPRESSION OF HEPATIC CYTOCHROME-P450 IN DWARF RATS - REVERSAL OF THE PROFILES BYGROWTH HORMONE-TREATMENT

A spontaneous dwarf rat derived from a colony of Sprague-Dawley (SD) s train has no detectable level of growth hormone (GH) in pituitary, alt hough it contained other hormones like prolactin and ACTH. Hepatic pro file of cytochrome P450 (P450) differed clearly between dwarf and norm al SD rats. A male-specific form of P450, CYP2C11, was detected in dwa rf male rat livers, while the level was one-third of the normal SD liv ers. This P450 was also detected in dwarf females. Other male-specific CYP3A2 and CYP3A18 were also contained in both sexes of dwarf rats, w hereas a female-specific form, CYP2C12, was not detectable in dwarf fe males. Phenobarbital-inducible CYP2B1 and CYP2B2 were constitutively e xpressed in dwarf rats, although substantially absent in normal SD rat s. To assess the role of GH on hepatic P450 expression, GH was given t o dwarf rats for 7 to 9 days. The intermittent injection (mimicking th e male secretory pattern) resulted in the elevation of CYP2C11 to a le vel as observed in normal SD males. Continuous infusion of GH (mimicki ng the female secretory pattern) evoked CYP2C12 in livers of both sexe s of dwarf rats, whereas the treatment decreased levels of CYP3A2, CYP 3A18, and CYP2B1. These results clearly demonstrate that specific defe ct of GH, but not pituitary, cause the clear changes in hepatic P450 f orms including sex-specific forms. The present study provides evidence further to strengthen the principal role of GH on the regulation of e xpression of P450 in rat livers. (C) 1997 Academic Press, Inc.