High levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in the ovary of the pregnant rabbit

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21 Scopus citations

Abstract

High levels of the rate-controlling enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase), developed in the rabbit ovary during pregnancy. Enzyme activity in homogenates of whole ovary rose from 0.5 nmol/min/mg of microsomal protein in the nonpregnant state to a peak level of 3 nmol.min-1.mg-1 on Day 5 of pregnancy. The highest specific activity of HMG CoA reductase (20 nmol.min-1.mg-1) was observed in the corpus luteum on Day 5 of pregnancy. Thereafter, enzyme activity in the corpus luteum declined to a level of 8 nmol.min-1.mg-1, which was maintained throughout the remainder of the 31-day gestational period. Throughout pregnancy, the specific activity of microsomal HMG CoA reductase in the interstitium was 8-to 10-fold lower than that of the corpus luteum. The elevation in HMG CoA reductase activity in homogenates of ovaries from pregnant, as compared with nonpregnant, rabbits was associated with a parallel increase in the rate of conversion of [14C]acetate to 14C-labeled nonsaponifiable lipids by ovarian slices. In the corpus luteum of the pregnant rabbit, cholesterol, pregnenolone, and progesterone accounted for the majority of the total 14C-labeled nonsaponifiable lipids synthesized from [14C]acetate. Feeding of cholesterol in amounts sufficient to elevate the plasma cholesterol level more than 30-fold did not prevent the increase in HMG CoA reductase activity in the ovary during pregnancy. The high levels of HMG CoA reductase activity occurred despite the presence of large amounts of stored cholesteryl esters within the corpus luteum. A marked enhancement in HMG CoA reductase activity was also observed when pseudopregnancy was induced by the administration of luteinizing hormone to virgin rabbits. The current data demonstrate that a portion of the cholesterol substrate for steroid hormone synthesis during pregnancy is synthesized within the ovary and that this is associated with a marked enhancement in HMG CoA reductase activity in the corpus luteum.

Original languageEnglish (US)
Pages (from-to)5126-5132
Number of pages7
JournalJournal of Biological Chemistry
Volume253
Issue number14
StatePublished - Dec 1 1978

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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