Inhibition of the Pregnenolone <i>Δ</i>⁵–3β-Hydroxysteroid Dehydrogenase-<i>Δ</i>^5-⁴ Isomerase Systems of Human Placenta and Corpus Luteum of Pregnancy

Abstract

The inhibition of the pregnenolone Δ⁵–3Β-hydroxysteroid dehydrogenase-Δ^5-4 isomerase systems in microsomes of human placenta or corpus luteum of pregnancy has been investigated using three steroidal substances: 2Α-cyano- 4,4,17Β-trimethylandrost-5-en-17Α-ol-3-one (cyanoketone), 2- hydroxymethylene, 17Α-methyl-5Α-androstan-17Β-ol-3-one (oxymetholone), and estradiol 17Β. The inhibition is of the competitive type with the synthetic steroids. The apparent K_i’s are approximately 0.3xl0^-5 M and 0.2xI0^-5 m for cyanoketone in the placental and ovarian systems, respectively, and the apparent K_i produced by oxymetholone is 0.6x10^-6 m in the ovarian system, however, that for the placental system is much smaller, 5.5xl0^-8 M. Approximately 50% inhibition was obtained in both systems with 2–5xl0^-5 M estradiol-17Β. Oxymetholone may be useful for the inhibition of corpora luteal function in women.

Expression of Estrogen Receptor α and β in the Rhesus Monkey Corpus Luteum during the Menstrual Cycle: Regulation by Luteinizing Hormone and Progesterone*

“…Estrogen has been shown to decrease luteal 3␤-hydroxysteroid dehydrogenase activity in vitro (50,51), providing a mechanism by which estrogens may further reduce luteal progesterone production in vivo. In the nonfertile menstrual cycle, decreasing LH pulse frequency (49) creates lengthening periods of relative progesterone deprivation, which may result in increased luteal ER␤ levels and enhanced luteal sensitivity to locally produced estrogens.…”

Control of the Menstrual Cycle

“…389,393 The self-destruct hypothesis was supported further by the observation that the addition of estradiol to isolated macaque luteal cells inhibited both basal and gonadotropin-stimulated progesterone production. 394,395 This attractive hypothesis, which would account for the observations that luteal regression does not appear to be due to a reduction in LH secretion, was questioned by subsequent observations in which sensitive bioassays were used to measure serum LH concentrations during estradiol-induced luteolysis. These studies revealed that estradiol-induced luteal regression was preceded by slight, but significant, declines in plasma LH concentrations during exposure to exogenous estradiol.…”

Inhibition by Estradiol of Human Chorionic Gonadotropin-Induced Progesterone Accumulation in Isolated Human Luteal Cells: Lack of Mediation by Prostaglandin F*

“…Another possibility might be that the in vitro inhibition by estradiol proceeds by a completely different mechanism than that in the in vivo effect. The former action could simply occur by direct inhibition of the A 5 -3/Miydroxysteroid dehydrogenase, A 5 ' 4 -isomerase system (13). Further studies will be necessary to resolve this difference.…”