Differential effect of trilostane on the progestin milieu in the pregnant mare.

The research article examines how trilostane, a steroid inhibitor, affects the progestin hormone environment in pregnant mares. The study concluded that trilostane does alter progestin metabolism without causing abortion, suggesting there’s a potential use of these findings in equine reproduction.

Objective

The researchers aimed to understand the role of trilostane, a drug that inhibits the enzyme 3 beta-hydroxysteroid dehydrogenase, on progestin hormones in pregnant mares. They wanted to test the effect of its infusion on progestin concentration in maternal plasma and its effect on placental metabolism.

Research Methodology

• The team administered trilostane intravenously to three mares between day 277 and day 282 of gestation.
• They also exposed placental tissue sampled from mares at the mid-gestation period (150-300 days) to two experimental treatments: administered deuterium-labelled pregnenolone alone or alongside trilostane.
• They collected blood samples at regular intervals for 48 hours after infusion and analyzed both plasma samples and incubation media following derivation.

Key Results

• They found that after 45 minutes of infusion, concentrations of some compounds (pregnenolone, 5-pregnene-3 beta, 20 beta-diol, 5 alpha-pregnane-3 beta,20 beta-diol and 3 beta-hydroxy-5 alpha-pregnan-20-one) increased and remained high for 37 hours.
• The concentrations of other compounds (5 alpha-pregnane-3,20-dione, 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 beta,20 alpha-diol) initially decreased 15 minutes after infusion but increased 1.5 hours later and stayed ensured for the next 37 hours.
• In vitro experiments demonstrated that trilostane inhibited the conversion of pregnenolone to progesterone but mediates an increase in other compounds’ concentrations.

Implications

The researchers concluded that pregnant mares have a unique metabolic activity concerning steroid hormones. The results suggest that a steroid other than progesterone, possibly 5 alpha-pregnane-3,20-dione, serves as the crucial steroid precursor for other progestin metabolites within circulating plasma. Trilostane, therefore, might play a role in manipulating equine reproductive hormone metabolism. These findings contribute to a better understanding of equine reproduction and potentially assist in enhancing fertility.