The importance of
progesterone biosynthesis and metabolism to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which exerts its effects via GABAA/
benzodiazepine receptor complexes (
GBRs) rather than intracellular
progestin receptors (PRs), was investigated for its effects on sexual receptivity.
Epostane, a 3beta-hydroxysteroid
dehydrogenase inhibitor, blocks
progesterone and 3alpha,5alpha-THP biosynthesis.
Finasteride, a 5alpha-reductase inhibitor, blocks the metabolism of
progesterone to
dihydroprogesterone (DHP), which is subsequently metabolized to 3alpha,5alpha-THP.
Indomethacin, a 3alpha-hydroxysteroid
oxidoreductase inhibitor, blocks DHP's metabolism to 3alpha,5alpha-THP, and its oxidation to DHP.
Epostane,
finasteride,
indomethacin or vehicle were infused intracranially in the ventral tegmental area (VTA) of
hormone-primed or naturally receptive rats and hamsters and sexual behaviour was recorded.
Epostane,
finasteride and
indomethacin to the VTA significantly reduced
lordosis, compared to vehicle infusions, in
hormone-primed and behavioural oestrous rats and hamsters. Radioimmunoassay revealed that concentrations of midbrain 3alpha,5alpha-THP were reduced following
epostane,
finasteride or
indomethacin infusions that significantly decreased
lordosis. Immunocytochemistry for 3alpha,5alpha-THP revealed the number of immunoreactive cells were significantly reduced in the VTA following
epostane,
finasteride or
indomethacin infusion to the VTA, but not other midbrain sites. These data suggest that biosynthesis of
progestins, and the metabolism of
progesterone to 3alpha,5alpha-THP in the VTA, are important for
progestin-facilitated sexual receptivity of rats and hamsters.