The effects of steroid hormones and gonadotropins on in vitro placental conversion of pregnenolone to progesterone.
Using human term placental mitochondrial preparations, optimal conversion of [3H]pregnenolone to [3H]progesterone was obtained at 30 min incubation and with a mitochondrial protein content of 2.5-3.5 mg/ml. Estradiol, estrone, progesterone and testosterone in a dose range of 0.03-8.66 mumol inhibited the in vitro conversion of [3H]pregnenolone to [3H]progesterone by placental homogenates. All four steroids inhibited the pregnenolone to progesterone conversion in a dose-dependent manner. The ID50 (dose required to inhibit conversion of pregnenolone to progesterone by 50%) was 0.04 mumol for estradiol, 0.13 mumol for testosterone, 0.3 mumol for progesterone and 1.0 mumol for estriol. Neither gonadotropin releasing hormone (50-1000 ng) nor human chorionic gonadotropin (5-500 IU) affected the placental basal conversion rate of pregnenolone to progesterone in vitro. Our findings indicate that steroid hormones such as estradiol, estrone, testosterone and progesterone can inhibit local placental progesterone biosynthesis through inhibition of the enzyme complex 5-ene-3 beta-hydroxysteroid dehydrogenase.
D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006062:Gonadotropins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000378:metabolism; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011284:Pregnenolone / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D010906:Pituitary Hormone-Releasing Hormones; D011374:Progesterone; D011284:Pregnenolone