INTERACTIONS OF GENDER, GROWTH-HORMONE, AND PHENOBARBITAL INDUCTION ON MURINE CYP2B EXPRESSION

The interactions of gender, growth hormone, and phenobarbital inductio n on Cyp2b expression were examined in phenotypically normal (lit/+)an d growth-hormone deficient ''little'' (lit/lit) mice. Using an immunoc rossreactive monoclonal antibody designed to identify rat CYP2B1 and 2 B2 proteins, we observed three hepatic Cyp2b proteins in control (lit/ +) females, but only two proteins, one at trace levels, in control mal es. Phenobarbital administration to lit/+ mice increased the expressio n of the two Cyp2b isoforms in the males by 3- to dr-fold, but produce d an approximately 75% reduction in the female expressed proteins. Whe reas growth hormone depletion (lit/lit) had no effect on the expressio n profile of Cyp2b proteins in females, it had a de-repressive effect in males, resulting in the expression of three proteins at concentrati ons now comparable to those observed in female liver. Generally, pheno barbital had no inductive effects in the lit/lit mice of both sexes. I n all groups, transcript levels measured by a CYP2B1 probe were in agr eement with the protein findings. In contrast, Cyp2b mRNA identified b y an oligonucleotide probe for CYP2B2 were repressed completely by gro wth hormone in both sexes, and was expressed as a female-predominant t ranscript in the lit/lit mice. In spite of an apparent high degree of sequence homology between the rat CYP2B and murine Cyp2b gene families , the present findings highlight fundamental differences in their cons titutive and gender dependent expression, growth hormone regulation, a nd phenobarbital inducibility. (C) 1998 Elsevier Science Inc.