Progesterone Catabolism in the Rat Ovary: A Regulatory Mechanism for Progestational Potency During Pregnancy1

Abstract

Changes in rat ovarian 20a-OH-SDH3 [20a-hydroxy steroid dehydrogenase] and G-6-PDH [glucos-6-phospho-dehydrogenase] activities as well as their intraglandular distribution during pregnancy, at parturition and during lactation have been determined concurrently with measurements of the peripheral blood and uterine tissue levels of progesterone and 20[alpha]-OH-P [20[alpha]-hydroxy-pregn-y-en-3-one]. In addition, effects of gonadotrophic hormones, hypophysectomy, placental dislocation and hysterectomy on the regulation of these enzyme activities have been examined. 20[alpha]-OH-SDH activity and 20[alpha]-OH-P concentrations decreased during early pregnancy as progesterone concentrations rose to a peak. At midgestation, day 7-12, a 2nd rise in plasma progesterone occurred accompanied by an increase in 20[alpha]-OH-P. No increase in 20[alpha]-OH-SDH was evident at this time. Between days 19 and 21 progesterone levels dropped sharply coincident with a rapid rise in ovarian 20[alpha]-OH-SDH and peripheral 20[alpha]-OH-P concentration. A high positive correlation existed between plasma 20[alpha]-OH-P concentrations and ovarian 20[alpha]-OH-SDH activities. Uterine and placental steroid concentrations reflected the fluctuations seen in plasma steroid levels; however, progesterone, not 20[alpha]-OH-P, appeared to be preferentially accumulated in uterine tissue. Involuting corpora lutea present during early pregnancy gave an intense histochemical reaction for both 20[alpha]-OH-SDH and G-6-PDH, but only G-6-PDH was present in corpora lutea of pregnancy, thecal cells and interstitia tissue. At midpregnancy G-6-PDH distribution was unaltered except for its disappearance from involuting corpora lutea. 20[alpha]-OH-SDH was not detectable histochemically during midgestation. On day 19 20a-OH-SDH activity developed in small loci distributed randomly in some corpora lutea of pregnancy and became uniformly distributed within all corpora by day 21. Enzyme activity increased logarithmically during this period. Hypophysectomy did not alter the rate of enzyme increase, but delayed the time of initiation about 4 hr. Luteinizing hormones (LH and HCG) administered at midpregnancy as well as total placental dislocation and hysterectomy increase 20[alpha]-OH-SDH and G-6-PDH activities. LtH administration following hysterectomy inhibited the increases in enzyme activity. Ovarian 20[alpha]-OH-SDH in suckling mothers was only 50% of that in mothers deprived of their litters. It is concluded that progesterone catabolism to 20[alpha]-OH-P constitutes a normal regulatory mechanism for reducing the progestational potency of rat ovarian secretions during pregnancy, that ovarian 20[alpha]-OH-SDH and G-6-PDH activities are under gonadotrophic hormone regulation, and that increased 20[alpha]-OH-SDH activity provides an index of the luteolytic process.