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Feminization imprinted by developmental growth hormone.

Sarmistha Banerjee1, Rajat K Das1, Bernard H Shapiro1

  • 1Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Molecular and Cellular Endocrinology
|September 1, 2018
PubMed
Summary
This summary is machine-generated.

Early growth hormone (GH) exposure imprints female rat liver drug metabolism enzymes. This early programming dictates permanent sex-specific enzyme expression patterns, challenging previous assumptions.

Keywords:
Cytochromes P450DevelopmentFeminizationGrowth hormoneImprintingSexual dimorphism

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Area of Science:

  • Endocrinology
  • Hepatology
  • Pharmacology

Background:

  • Sex-specific regulation of hepatic drug-metabolizing enzymes (cytochromes P450 or CYPs) is permanent in adult females.
  • The role of hormonal imprinting in female mammalian development is not fully understood.
  • Previous work identified early growth hormone (GH) exposure as critical for programming male-specific CYP enzyme masculinization.

Purpose of the Study:

  • To investigate the role of early developmental GH exposure in programming female-specific hepatic CYP expression.
  • To determine if early GH exposure imprints the permanent sex-dependent regulation of hepatic CYPs in females.
  • To elucidate the differential regulation of specific CYP enzymes by adult GH profiles.

Main Methods:

  • Newborn female rats had GH secretion selectively blocked.
  • Some rats received concurrent GH replacement or GH-releasing factor.
  • Adult CYP2C12, CYP2C7, CYP2C6, and CYP2E1 expression levels were measured in relation to GH profiles.

Main Results:

  • Early GH exposure imprints the expression of female-specific CYP2C12 and CYP2C7, making them dependent on the adult feminine GH profile.
  • Female-predominant CYP2C6 and CYP2E1 expression is inversely related to GH levels, suppressed by both feminine and masculine GH profiles.
  • Blocking early GH secretion altered adult enzyme expression, which was partially restored with GH treatment.

Conclusions:

  • Early developmental GH exposure permanently imprints the expression patterns of specific hepatic CYPs in female rats.
  • This imprinting establishes a lifelong dependence of CYP2C12 and CYP2C7 on the adult feminine GH profile.
  • The regulation of CYP2C6 and CYP2E1 in adult females does not appear to require GH imprinting, but is influenced by adult GH levels.