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Growth hormone: a newly identified developmental organizer
Rajat K Das, Sarmistha Banerjee, Bernard H Shapiro1
1Department of Biomedical SciencesUniversity of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, USA shapirob@vet.upenn.edu.
The Journal of Endocrinology
|December 17, 2016
Summary
Perinatal growth hormone (GH) imprinting is essential for adult male sex differences in drug metabolism. Without this early imprinting, key drug-metabolizing enzymes like CYP2C11 are permanently suppressed, impacting health.
Area of Science:
- Endocrinology
- Pharmacology
- Developmental Biology
Background:
- Sex differences in cytochrome P450 (CYP) drug-metabolizing enzymes emerge in adulthood.
- These differences are regulated by circulating growth hormone (GH) profiles.
- Adult CYP expression patterns appear permanent, suggesting a critical imprinting event.
Purpose of the Study:
- To investigate the role of perinatal growth hormone (GH) in imprinting adult sex-specific CYP expression.
- To determine if GH imprinting is necessary for the adult regulation of CYP2C11 expression and drug metabolism in males.
Main Methods:
- Newborn male rats had their GH secretion selectively blocked or received concurrent GH replacement.
- Adult CYP2C11 isoform expression and drug metabolism were assessed in these rats.
Main Results:
- Adult male GH activation of the signaling pathway for CYP2C11 is critically dependent on perinatal GH imprinting.
- Lack of perinatal GH imprinting resulted in permanent and profound suppression of CYP2C11 and drug metabolism.
- This imprinting is specific to the perinatal period.
Conclusions:
- Perinatal GH imprinting is an obligate requirement for establishing normal adult male-specific CYP2C11 expression and drug metabolism.
- Pediatric therapies that disrupt GH secretion may have long-term adverse effects on adult drug metabolism and health.
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