Metabolism of progesterone by placentas from several mammalian species in vitro

20-alpha-Hydroxysteroid oxidoreductase (20-alpha-HSDH) activity and 20-alpha-dihydroprogesterone concentration (20-alpha-DHP) reach peak values in the human placenta after vaginal delivery. To determine if these findings are unique to the human, we measured 20-alpha-HSDH activity as well as endogenous progesterone (P) and 20-alpha-DHP concentration in the soluble supernatant fraction of placental tissues obtained from rodents (rat, rabbit, guinea pig), ungulates (horse, zebra, giraffe, cow), and primates (squirrel monkey, orangutan, man). P concentration was very low in rodents (mean 0.60 ng/mg protein), increased slightly in ungulates (mean 2.89 ng/mg protein), and reached a maximum value in the human (34.43 ng/mg protein). 20-alpha-DHP concentration had a strong positive correlation (r = 0.93) with P tissue content; it was low in rodents (mean 0.21 ng/mg protein), increased slightly in ungulates (mean 0.79 ng/mg protein), and reached a maximum value in the human (39.53 ng/mg protein). 20-alpha-HSDH activity, however, had a poor correlation with 20-alpha-DHP tissue concentrations: Its lowest value was in the guinea pig (9.34 pmole/mg protein/hour) and the highest was in the horse (3.19 nmole/mg protein/hour). These results indicate that a high level of activity of the P to 20-alpha-DHP pathway with significant tissue accumulation of 20-alpha-DHP is unique to the human placenta and reinforce the possibility of its causing in situ P withdrawal as a part of the overall mechanism of human parturition.