REDUCTIVE PATHWAYS OF PROGESTERONE METABOLISM IN THE RAT OVARY
ABSTRACT Progesterone underwent extensive reductive metabolism when incubated with a microsomal preparation from rat ovaries in the presence of NADPH. The major products formed were 3β-hydroxy-5α-pregnan-20-one, 5α-pregnane-3,20-dione and 5α-pregnane-3β,20α-diol. Newly formed corpora lutea of pregnancy were almost devoid of any microsomal A-ring reducing activity (5α-reductase and a 3β-hydroxysteroid dehydrogenase) and of soluble 20α-hydroxysteroid dehydrogenase. The behaviour of the A-ring reducing enzymes paralleled that of 20α-ol dehydrogenase in that their activity (i) was high during the oestrous cycle; (ii) declined between the third and seventh day of pregnancy; and (iii) increased sharply in corpora lutea of pregnancy when ergocornine – a drug blocking pituitary prolactin secretion – was given to the rats, yet remained low when prolactin and ergocornine were administered concurrently. However, the A-ring reducing activity did not show the sharp pre-partum rise exhibited by 20α-ol dehydrogenase, thus deviating from a pattern compatible with a co-ordinate control of the three enzymes involved in the metabolic inactivation of progesterone. Contrary to a report in the literature, 5α-pregnane-3,20-dione (20 mg/rat/day) was found to be ineffective when tested for pregnancy or deciduoma supporting activity in ovariectomized rats. The microsomal reductases, if indeed operative in vivo, may restrict the availability of progesterone as an oestrogen precursor.