Study of progesterone production in humanm pregnancy by early placental explants

Little is known about the factors stimulating placental progesterone (P4) production at the time of the luteo-placental shift (6-8 weeks post-conception). To explore the regulatory mechanism, the effects of various steroids and peptides on the production of P4 by placental explants were studied.In early placental explant culture P4 production was stimulated by 19-nortestosterone (19-NT), androstenedione (A-dione), 5$ alpha$-androstane-3$ alpha,$17$ beta$ diol (3$ alpha$-diol) and 5$ alpha$-androstane-3$ beta,$17$ beta$ diol (3$ beta$-diol). Of all the compounds tested, 19-NT had maximal effect. At term, P4 production was stimulated only by 3$ beta$-diol. 19-NT and A-dione were poorly aromatized in early placental explants compared to another androgen (Androst-5-ene-3$ beta,$17$ beta$ diol).In accord with the above observations, placental levels of 19-NT and A-dione were higher in early gestation while the diols were higher in late gestation.19-NT stimulated P4 production in early placenta by effects on the conversion of P4 both from 25-hydroxycholesterol and from pregnenolone. The stimulatory influences of A-dione and 3$ alpha$-diol were mediated by increasing the P450scc activity. The specific increase of the conversion of P4 from pregnenolone accounted for the P4 stimulation observed by 3$ beta$- diol treatment of culture.Cyloheximide (CH) treatment abolished the stimulatory influences of the aforementioned steroids on P4 production except for the initial phase of P4 stimulation by 19-NT, suggesting that all but the latter are dependent on protein synthesis.P4 production was also stimulated and prolonged to 30 days in the presence of human maternal serum (HMS); a good correlation (r = 0.74, P $<$ 0.05) was seen between the histological appearance of the explants and P4 production. The stimulatory activity of HMS was heat labile, non-dialyzable and non-extractable into an organic solvent, suggesting that it is protein in nature.In conclusion, this study suggests that 19-NT and A-dione are important for placental P4 production at the time of the luteo-placental shift. For in vitro study of placental hormonal regulation, HMS is a better nutrient supplement than fetal bovine serum