INVITRO STIMULATION OF PLACENTAL PROGESTERONE PRODUCTION BY 19-NORTESTOSTERONE AND C-19 STEROIDS IN EARLY HUMAN-PREGNANCY

To explore the regulatory mechanism at the critical period of the luteal-placental shift, the effects of various steroids and peptides on the production of progesterone by placental explants at 7-10 weeks were studied. Androstenedione increased progesterone production 3-fold at a concentration of 1-mu-mol and more than 20-fold at 18-mu-mol. 19-Nortestosterone (1-18-mu-mol) stimulated progesterone production 10- to 100-fold. 5-alpha-androstane-3-beta,17-beta diol (1-18-mu-mol) stimulated progesterone production about 2- to 5-fold while its 3-alpha isomer (1-6-mu-mol) increased it 2-fold. Estrone, estradiol, and estriol up to a concentration of 30-mu-mol had no effect. Dehydroepiandrosterone sulfate (to 36-mu-mol), androst-5-ene-3-beta,17-beta diol (1-6-mu-mol), 5-beta-androstane-3-alpha,17-beta diol (1-6-mu-mol), and dihydrotestosterone (1-12-mu-mol) had no effect. Cortisol and dexamethasone (up to 12-mu-mol), hCG (20,000 IU/L), GnRH (4-mu-mol), and ACTH 1-24 (20-mu-mol) also had no effect. Thus, of all the compounds tested, only 19-nortestosterone and, to a lesser extent, androstenedione, 5-alpha-androstane-3-beta,17-beta diol, and 5-alpha-androstane-3-alpha,17-beta diol stimulated progesterone production in early pregnancy; at term, only 5-alpha-androstane-3-beta,17-beta diol was stimulatory. 19-Nortestosterone was found to be less efficiently aromatized compared to other androgens; since it is also known to be present in blood from pregnant women and thought to be made in the placenta, the stimulation observed may be a paracrine effect. These observations suggest that C18 and C19 steroids may be important in the regulation of progesterone synthesis by the human placenta in early pregnancy.