In vitro stimulation of placental progesterone production by 19-nortestosterone and C19 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 mumol and more than 20-fold at 18 mumol. 19-Nortestosterone (1-18 mumol) stimulated progesterone production 10- to 100-fold. 5 alpha-Androstane-3 beta,17 beta diol (1-18 mumol) stimulated progesterone production about 2- to 5-fold while its 3 alpha isomer (1-6 mumol) increased it 2-fold. Estrone, estradiol, and estriol up to a concentration of 30 mumol had no effect. Dehydroepiandrosterone sulfate (to 36 mumol), androst-5-ene-3 beta,17 beta diol (1-6 mumol), 5 beta-androstane-3 alpha,17 beta diol (1-6 mumol), and dihydrotestosterone (1-12 mumol) had no effect. Cortisol and dexamethasone (up to 12 mumol), hCG (20,000 IU/L), GnRH (4 mumol), and ACTH 1-24 (20 mumol) 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.
Begum-Hasan
J
J
Reproductive Physiology Unit, Montreal General Hospital, Quebec, Canada.
Murphy
B E
BE
D002845:Chromatography; D046508:Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D036861:Delivery, Obstetric; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D009277:Nandrolone / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011261:Pregnancy Trimester, First; D011355:Prodrugs / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D013256:Steroids / Q000494:pharmacology*; D013997:Time Factors
D011355:Prodrugs; D013256:Steroids; D011374:Progesterone; D004958:Estradiol; D009277:Nandrolone; D003513:Cycloheximide