[Expressions of SHP and CYP7A1 in pregnant rats with intrahepatic cholestasis].
OBJECTIVE
To investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP.


METHODS
Thirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot.


RESULTS
(1) In the EB group, the serum levels of ALT, AST, ALP, TBA, TBil, and DBil after EB administration increased significantly (P less than 0.01), but there were no significant changes in the NS group (P more than 0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365+/-0.0317 vs EB 0.4865+/-0.0237, P less than 0.01), (CYP7A1 mRNA: NS 0.3570+/-0.0175 vs EB 0.4802+/-0.0217, P less than 0.01)]; (4) The protein expressions of SHP and CYP7A1 were also higher in the EB group than that in the NS group [(SHP: NS 0.3762+/-0.0284 vs EB 0.5033+/-0.0274, P less than 0.01), (CYP7A1: NS 0.3570+/-0.0175 vs EB 0.4802+/-0.0217, P less than 0.01)].


CONCLUSIONS
Estrogen induces ICP in rats. The mRNA and protein expressions of SHP and CYP7A1 in livers of the ICP rats were increased, which causes more bile acids to be synthesized. This may be one of the mechanisms of ICP.
Lan
Yi
Y
Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Liu
Jian
J
Cheng
Hao
H
Zou
Shu-li
SL
Gan
Xiao-ling
XL
D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; C074283:estradiol 3-benzoate; D004958:Estradiol; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase