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Research ArticleArticle

Prolactin Upregulates Female-Predominant P450 Gene Expressions and Downregulates Male-Predominant Gene Expressions in Mouse Liver

Yuya Sato, Yoshikatsu Kaneko, Takamasa Cho, Kei Goto, Tadashi Otsuka, Suguru Yamamoto, Shin Goto, Hiroki Maruyama and Ichiei Narita
Drug Metabolism and Disposition June 2017, 45 (6) 586-592; DOI: https://doi.org/10.1124/dmd.116.074658
Yuya Sato
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Yoshikatsu Kaneko
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Takamasa Cho
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Kei Goto
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Tadashi Otsuka
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Suguru Yamamoto
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Shin Goto
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Hiroki Maruyama
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Ichiei Narita
Division of Clinical Nephrology and Rheumatology (Y.S., Y.K., T.C., K.G., T.O., S.Y., S.G., I.N.) and Department of Clinical Nephroscience (H.M.), Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan
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Abstract

Prolactin is a polypeptide hormone with over 300 separate biologic activities. Its serum level is increased during pregnancy and lactation, and it has been reported that pregnancy and lactation affect drug and steroid metabolism in mice and humans. Several studies reported that pregnancy or lactation influences liver cytochrome P450 (P450) expression and its activity, affecting the biosynthesis of steroids and xenobiotics through growth hormone or sex hormones; however, the role of prolactin as the regulator of liver P450 expression has not been elucidated so far. In the present study, we focused on prolactin as the regulator of expression of liver sex-predominant genes, including P450s. To investigate the role of prolactin in the hepatic gene expressions, pCAGGS expression vector containing mouse prolactin cDNA was transfected by hydrodynamic injection into both male and female mice. Hyperprolactinemia phosphorylated signal transducer and activator of transcription 5 in the liver and augmented female mouse liver mRNA expression of Cyp3a16, Cyp3a41, Cyp3a44, Cyp2b9, and prolactin receptor genes, whose expressions were female-predominant in hepatocytes. Moreover, liver expression of male-predominant genes such as Cyp2d9, Cyp7b1, Mup1, and Alas2 were reduced in male mice with hyperprolactinemia. The serum levels of conventional regulators of hepatic gene expressions, growth hormone, and testosterone were not affected by hyperprolactinemia. We demonstrated that prolactin upregulated female-predominant genes in female mice and downregulated male-predominant genes in male mice. We conjecture that higher concentration of prolactin would alter steroid and xenobiotic metabolisms by modulating hepatic P450 gene expressions during pregnancy and lactation.

Footnotes

    • Received December 15, 2016.
    • Accepted March 17, 2017.
  • This work was partly supported by JSPS KAKENHI [Grant JP24591191] and NOVARTIS Foundation for Gerontological Research.

  • https://doi.org/10.1124/dmd.116.074658.

  • Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 45 (6)
Drug Metabolism and Disposition
Vol. 45, Issue 6
1 Jun 2017
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Research ArticleArticle

Prolactin and Sex-Predominant Gene Expressions in the Liver

Yuya Sato, Yoshikatsu Kaneko, Takamasa Cho, Kei Goto, Tadashi Otsuka, Suguru Yamamoto, Shin Goto, Hiroki Maruyama and Ichiei Narita
Drug Metabolism and Disposition June 1, 2017, 45 (6) 586-592; DOI: https://doi.org/10.1124/dmd.116.074658

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Research ArticleArticle

Prolactin and Sex-Predominant Gene Expressions in the Liver

Yuya Sato, Yoshikatsu Kaneko, Takamasa Cho, Kei Goto, Tadashi Otsuka, Suguru Yamamoto, Shin Goto, Hiroki Maruyama and Ichiei Narita
Drug Metabolism and Disposition June 1, 2017, 45 (6) 586-592; DOI: https://doi.org/10.1124/dmd.116.074658
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