Effects of inhibiting 3 beta-hydroxysteroid dehydrogenase on plasma progesterone and other steroids in the pregnant mare near term.

The research investigated the impact of inhibiting 3 beta-HSD, an enzyme involved in steroid production, on the levels of progesterone and other steroids in pregnant horses near the end of their terms. They found that blocking 3 beta-HSD led to notable changes in steroidogenesis, but appeared to have minimal effect on the duration of pregnancy.

Introduction and Objectives

In the study, researchers examined the effects of inhibiting 3 beta-Hydroxysteroid Dehydrogenase (3 beta-HSD), an enzyme crucial for steroidogenesis, in pregnant horses (mares) nearing the end of their gestation period. Steroidogenesis is the biological process by which steroids are generated from cholesterol, and one of these steroids is progesterone, a hormone important for pregnancy. The ultimate aim of the study was to analyze how alterations in steroidogenesis might affect the length of gestation.

Methodology

• The researchers administered Epostane, an inhibitor of 3 beta-HSD, via intravenous infusion to a pregnant mare between 292 and 330 days of gestation. The doses ranged from 1-3 mg/kg/min.
• The subsequent effects on progesterone levels in the bloodstream (both in the artery and uterine vein) were closely monitored.
• The venous-arterial (V-A) difference in progesterone concentration across the uterus pre and post Epostane infusion was also measured.
• As a control experiment, comparable monitoring was performed in mares infused with a vehicle alone, i.e., without the 3 beta-HSD inhibitor.

Key Findings

• Epostane infusion caused a rapid and significant reduction in plasma progesterone concentrations both in the artery and uterine vein, which persisted for about four to five hours.
• The V-A concentration difference in progesterone across the uterus also fell significantly with Epostane treatment.
• Unlike the case in treated subjects, the control group did not register significant changes in their plasma progesterone concentrations or V-A concentration differences.
• The concentration of total unconjugated oestrogens in the uterine vein also decreased with Epostane administration. In contrast, it remained unchanged in the control cases.
• Initial infusion of Epostane led to reduced arterial plasma cortisol levels, but these levels later increased significantly.
• Importantly, none of the mares delivered after Epostane treatment, indicating that inhibiting 3 beta-HSD might not affect the length of gestation.

Conclusion

Overall, this study shows that inhibiting 3 beta-HSD can significantly alter steroidogenesis. In particular, it affects the concentrations of progesterone and some other steroids in pregnant mares’ bloodstreams. However, this interference with steroid production seems to have little impact on the duration of the pregnancy. More research is still necessary to understand the full effects and potential implications of inhibiting 3 beta-HSD.