Dehydroepiandrosterone synthesis by the fetal foal and its importance as an oestrogen precursor.

The study explores the process of dehydroepiandrosterone (DHA) synthesis in the fetal foal and its significance as a precursor to the hormone oestrogen. It debunks the idea of the fetal liver’s role in equilin synthesis but confirms DHA’s role as an oestrogen precursor.

Examination of Gonads and Enzyme Activity

• The researchers found that the gonads of a fetal horse are relatively devoid of 3 beta-hydroxysteroid dehydrogenase and other enzymes which metabolize dehydroepiandrosterone (DHA).
• This implies that DHA might not undergo much modification at the gonadal level in the fetal horse.

In-Vitro Conversion Experiments

• Short-term in-vitro incubation experiments were conducted where it was observed that the fetal liver converted DHA into the potential equilin precursor, 7 alpha-hydroxy DHA.
• In contrast, when DHA was incubated with extracts of horse placenta, DHA was converted to oestrone. However, 7 alpha-hydroxy DHA was not converted to equilin. This indicated that the conversion process for DHA might be different in the placenta as compared to the liver.

DHA and Oestrogen Levels During Pregnancy

• DHA levels in the blood of mares during pregnancy were found to parallel those of equilin and oestrone. However, DHA concentrations sharply dropped following the surgery to remove the fetal gonads – showing a correlation between DHA levels and the presence of the fetal gonads.
• This observation points to the fact that DHA might have a role in the formation of oestrogen (equilin and oestrone) in mares during pregnancy.

Isotope Administration and Hormone Analysis

• The researchers administered labelled DHA isotopes to the fetus. Both isotopes were integrated into maternal urinary oestrone but were not present in urinary equilin.
• This allowed the researchers to confirm DHA’s role as a precursor to oestrone. However, it also refuted the earlier idea of the fetal liver’s role in equilin synthesis.
• The team suggested an alternative synthesis route for equilin that might diverge from the terpenoid steroid synthetic route before DHA is formed.

In conclusion, the research reaffirms the importance of DHA in contributing to oestrogen formation during horse pregnancy, while also providing new insights into the biosynthesis of equilin.