Prolactin Upregulates Female-PredominantP450Gene Expressions and Downregulates Male-Predominant Gene Expressions in Mouse Liver.
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 liverP450expression has not been elucidated so far. In the present study, we focused on prolactin as the regulator of expression of liver sex-predominant genes, includingP450s.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 ofCyp3a16,Cyp3a41,Cyp3a44,Cyp2b9, and prolactin receptor genes, whose expressions were female-predominant in hepatocytes. Moreover, liver expression of male-predominant genes such asCyp2d9,Cyp7b1,Mup1, andAlas2were 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 hepaticP450gene expressions during pregnancy and lactation.
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.
Yuya
Y
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 kanekoy@med.niigata-u.ac.jp.
Yoshikatsu
Y
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.
Takamasa
T
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.
Kei
K
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.
Tadashi
T
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.
Suguru
S
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.
Shin
S
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.
Hiroki
H
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.
Ichiei
I
Narita
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013739:Testosterone / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
D012333:RNA, Messenger; D013739:Testosterone; D011388:Prolactin; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System