Sex steroids increase cholesterol 7alpha-hydroxylase mRNA in nonhuman primates.
One mechanism that may account for our prior observation that oral contraceptives decrease the hepatic cholesterol concentration independently of the low-density lipoprotein (LDL) receptor in sexually intact nonhuman primates is that sex hormones increase biliary cholesterol secretion by increasing hepatic mRNA abundance for cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in the conversion of cholesterol into bile acids. To examine the independent effect of estrogen, progestin, and combined estrogen and progestin on the hepatic cholesterol concentration and cholesterol 7alpha-hydroxylase mRNA abundance, 34 ovariectomized adult female cynomolgus monkeys were fed a moderately atherogenic diet for 12 weeks with either oral conjugated equine estrogen ([CEE] n = 8), medroxyprogesterone acetate ([MPA] n = 9), or combined CEE + MPA (n = 9) and compared with a control group (n = 8) that did not receive exogenous sex hormones. After 12 weeks, hepatic cholesterol was significantly lower in CEE-treated (6.2 +/- 1.2 mg/g liver) and CEE + MPA-treated (6.4 +/- 0.9 mg/g liver) animals compared with the control (12.6 +/- 1.9 mg/g liver) and MPA-treated (14.6 +/- 1.6 mg/g liver) groups. Hepatic cholesterol 7alpha-hydroxylase mRNA abundance was significantly increased in CEE-treated (0.553 +/- 0.08 pg/microg RNA), MPA-treated (0.734 +/- 0.12 pg/microg RNA), and CEE + MPA-treated (0.487 +/- 0.07 pg/microg RNA) animals compared with the controls (0.318 +/- 0.03 pg/microg RNA). There was no significant difference in the plasma LDL cholesterol concentration and hepatic LDL receptor mRNA abundance between the groups. These data support but do not prove the hypothesis that low-dose oral estrogen induces an increase in cholesterol 7alpha-hydroxylase mRNA abundance, which is correlated with biliary cholesterol secretion and may result in depletion of hepatic cholesterol.
Colvin
P L
PL
Department of Internal Medicine, University of Maryland School of Medicine and the Baltimore Veterans Affairs Medical Center, Geriatrics Research, Education, and Clinical Center, 21201-1524, USA.
Wagner
J D
JD
Adams
M R
MR
Sorci-Thomas
M G
MG
D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D005260:Female; D008252:Macaca fascicularis; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*
D011372:Progestins; D012333:RNA, Messenger; D002790:Cholesterol 7-alpha-Hydroxylase