In vitro 19-norandrogen synthesis by equine placenta requires the participation of aromatase.

This research investigates how the equine placenta synthesizes 19-norandrogens, a type of hormone, and suggests that a part of these 19-norandrogens found in the blood of pregnant mares originates from the placenta itself. The work shows that this synthesizing process relies on the presence of the enzyme aromatase.

Methods and Findings

• The researchers used explants of full-term equine placenta to observe if they can synthesize 19-norandrogens from labelled androgens, which are forms of hormones. It was found that the equine placenta can indeed synthesize the 19-norandrostenedione variant of 19-norandrogens.
• The synthesized hormones were then purified and evaluated. A significant task was done to recrystallize the 19-Norandrostenedione to constant-specific activity, which provided indisputable proof for its synthesis by the equine placenta.
• The synthesizing process was found to occur more likely in the microsomal fraction. When compared with other substrates used, the production of 19-norandrogens was much weaker than that of oestrogens. Moreover, the yield of 19-norandrogens that were 17-oxosteroids was considerably more than those that were 17 beta-hydroxysteroids. These findings indicate the presence of a dehydrogenase enzyme with a strong oxidative activity.
• Most of the synthesized steroids were found to be unconjugated, with sulphoconjugated steroids comprising less than 0.5% of total steroids.

Role of Aromatase

• While 19-nortestosterone failed to be produced through equine purified aromatase, the use of two specific aromatase inhibitors, 4-hydroxyandrostenedione and fadrozole, was found to halt the synthesis of 19-norandrogens as well as oestrogens in the equine placental explants. This suggests that aromatase plays a significant role in the biosynthesis of these hormones.

Implications of the Findings

• The research provides evidence that at least part of the 19-norandrogens found in the blood of pregnant mares stems from the placenta. It also puts forward a hypothesis that the synthesis of 19-norandrogens might involve the enzymatic metabolism of 19-oxygenated androgens formed by the equine aromatase enzyme.