Synergism of glucocorticoid hormone with growth hormone for female-specific mouse Cyp3a44 gene expression.
CYP3A44 and CYP3A41 are female-specific CYP3A in the mouse liver. In primary cultured mouse hepatocytes, dexamethasone concentration-dependently induced CYP3A44 mRNA, and the highest response was seen at 10(-5) M. In contrast, CYP3A41 mRNA expression was highest at lower concentrations (10(-7) or 10(-6) M). At submicromolar concentration (10(-7) M), the induction of CYP3A44 mRNA was very slight, but strongly enhanced induction was observed by the simultaneous addition of growth hormone (GH). Similar enhancement was also observed in CYP3A41 mRNA expression. Continuous exposure to GH, which mimics female-type secretion from the pituitary gland, was effective to enhance the expression of both mRNAs, but discontinuous exposure (male-type) was not. This synergistic induction of CYP3A44 mRNA was further enhanced by the transfection of glucocorticoid receptor (GR) expression plasmid or by the cotransfection of pregnane X receptor (PXR) and retinoid X receptor (RXR) alpha expression plasmids. Similar synergistic induction was seen in CYP3A41 mRNA by the transfection of GR expression plasmid but was not enhanced by cotransfection of PXR and RXR expression plasmids. These observations suggest that functional cross-talk between signaling pathways of female-type GH secretion and glucocorticoid hormone might be involved in the female-predominant expression of both genes. Additionally, one or more nuclear receptors mediating induction by glucocorticoid hormone are employed for collaboration with GH.
Sakuma
Tsutomu
T
Department of Toxicology, Graduate School of Medicine and Pharmaceutical, Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 Japan.
Bhadhprasit
Wattanaporn
W
Hashita
Tadahiro
T
Nemoto
Nobuo
N
D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D012970:Sodium Glutamate / Q000494:pharmacology
C464819:Cyp3a44 protein, mouse; D005938:Glucocorticoids; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D047490:Retinoid X Receptor alpha; D015735:Mifepristone; D003907:Dexamethasone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; C408695:Cyp3a41a protein, mouse; D012970:Sodium Glutamate; D003345:Corticosterone; D006854:Hydrocortisone