title: Growth hormone: a newly identified developmental organizer.
abstract: The sexually dimorphic expression of cytochromes P450 (CYP) drug-metabolizing enzymes has been reported in all species examined. These sex differences are only expressed during adulthood and are solely regulated by sex differences in circulating growth hormone (GH) profiles. Once established, however, the different male- and female-dependent CYP isoform profiles are permanent and immutable, suggesting that adult CYP expression requires imprinting. As the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectively blocked GH secretion in some newborn male rats, whereas others received concurrent physiologic replacement of rat GH. The results demonstrate that adult male GH activation of the signal transduction pathway regulating expression of the principal CYP2C11 isoform is obligatorily dependent on perinatal GH imprinting, without which CYP2C11 and drug metabolism would be permanently and profoundly suppressed. As there are other adult metabolic functions also regulated by GH, pediatric drug therapy known to disrupt GH secretion could unintentionally impair adult health.
authors.forename: Rajat K
authors.initials: RK
authors.lastname: Das
authors.forename: Sarmistha
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Biomedical SciencesUniversity of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, USA shapirob@vet.upenn.edu.
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D000072467:Cytochrome P450 Family 2; D013006:Growth Hormone; D039181:Steroid 16-alpha-Hydroxylase; D050826:Suppressor of Cytokine Signaling Proteins; C450279:CYP2C11 protein, rat
keywords: CYP2C11; JAK/STAT; growth hormone; imprinting; miRNA