Indirect regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by oestradiol in the rabbit corpus luteum

Rabbits were given 50 i.u. hCG, i.v., to initiate ovulation and pseudopregnancy (Day 0) and were treated, s.c., with or without a 1-cm Silastic oestradiol implant. Serum progesterone concentrations were measured at 4-day intervals and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was estimated by the conversion of HMG to mevalonate in microsomes from corpora lutea removed on Days 4, 8, 12, 16 and 20 of pseudopregnancy (4 rabbits/day). Total HMG-CoA reductase activity was significantly (P less than 0.05) higher in control rabbits on Days 8 and 12 (5.29 +/- 0.63 and 5.5 +/- 0.28 nmol/min/mg protein, respectively) compared to oestradiol-treated rabbits (2.57 +/- 0.25 and 4.03 +/- 0.23 nmol/min/mg protein, respectively). On Days 16 and 20, total HMG-CoA reductase activity was not different in control and oestradiol-treated animals. There was no difference in the levels of the active fraction of HMG-CoA reductase, which represented less than 20% of the total enzyme activity, in control and oestradiol-treated rabbits (less than 780 pmol/min/mg protein, Day 12). These results indicate that oestradiol does not alter the active form, but can reduce the total activity of HMG-CoA reductase in the rabbit corpus luteum without a decline in serum progesterone. Therefore, neither total nor active forms of HMG-CoA reductase are directly related to progesterone secretion. This suggests that other sources of cholesterol may contribute to progesterone production in the rabbit.