title: Estrogen regulates placental androstenedione production during rat pregnancy.
abstract: During rat pregnancy the placenta appears to provide androgens, particularly androstenedione (delta 4A) as a source of precursor for estradiol (E2) formation by the ovary. The present study determined if the ovary and, specifically, estrogen have roles in regulating placental delta 4A production during the second half of rat pregnancy. Pregnant rats were ovariectomized (OVX) on day 9 of gestation, treated daily with 4 mg progesterone (P4) to maintain pregnancy, and received a Silastic capsule containing either E2 or oil on day 10 of gestation only. Placental steroidogenesis was then determined in vitro on day 14 by the ability of this tissue to convert [3H]pregnenolone ([3H]P5) substrate to the intermediate [3H]P4 and product [3H]delta 4A. Mean (+/- SE) placental formation of delta 4A from P5 increased (P less than 0.01) from 6.3 +/- 0.5% in control animals to 10.7 +/- 1.6% in OVX P4-treated rats. In contrast, placentae from OVX animals treated with P4 and E2 exhibited a decline in delta 4A formation (2.5 +/- 0.3%) compared to that in both control (P less than 0.01) and OVX P4-treated (P less than 0.001) animals. The amount of P5 converted to P4 and thus not further metabolized to delta 4A decreased (P less than 0.05) from 64.0 +/- 3.1% in control animals to 49.0 +/- 4.7% in OVX rats treated with P4 alone. However, OVX animals treated with P4 and E2 exhibited an increase in placental conversion of P5 to P4 (80.3 +/- 4.7%) compared to values in both control (P less than 0.05) and OVX P4-treated (P less than 0.001) animals. The peripheral serum concentrations of delta 4A and testosterone (T) were 3- and 2-fold greater (P less than 0.01), respectively, in OVX P4-treated animals compared to concentrations in the untreated controls. Rats that had been OVX and treated with both P4 and E2 had peripheral serum delta 4A and T concentrations that were approximately 10-15% (P less than 0.001) of the concentrations in OVX P4-treated animals. In conclusion, ovariectomy or ovariectomy and estrogen supplementation resulted in comparable alterations in the formation of delta 4A within the placenta and the concentrations of this steroid in the peripheral circulation. Thus, ovariectomy caused an elevation in and ovariectomy with E2 treatment caused a decline in both placental delta 4A formation and peripheral serum androgen concentrations. We suggest, therefore, that ovarian estrogen may feed back to inhibit placental delta 4A and T production, thereby regulating its substrate availability during the second half of rat pregnancy.
mesh_terms: D000735:Androstenedione / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood
chemical_list: D004967:Estrogens; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol