title: Modulatory action of benzodiazepines on human term placental steroidogenesis in vitro.
abstract: Peripheral benzodiazepine (BZ) binding sites (PBzS) were characterized on placental explant membranes. [3H]PK 11195, an isoquinoline carboxamide derivative, which is a ligand specific for PBzS, labeled these sites with an equilibrium dissociation constant of 2.1 nM; the maximal number of binding sites was 396 fmol/mg protein. The effect of various BZ ligands and PK 11195 on the secretion of progesterone (P4) and estradiol-17 beta (E2) from human term placental explants was studied. Exposure of placental explants to low doses (10(-8) M) of Ro 5-4864, a BZ ligand which binds with high affinity to PBzS, caused a significant (P less than 0.05) increase in the secretion of P4 and E2 into the media (2.4- and 1.4-fold, respectively). On the other hand, high doses (10(-5) M) of Ro 5-4864 caused a significant (P less than 0.05) decrease in the secretion of P4 and E2 into the media. Also, exposure of explants to diazepam (10(-7) M) and PK 11195 (10(-6) M) caused a significant increase in P4 and E2 secretion into the media. In contrast, clonazepam, a BZ ligand specific for the central-type receptors, had no effect on the secretion of either steroid. The combination of diazepam (10(-7) M) or Ro 5-4864 (10(-8) M) with PK 11195 (10(-6) M) did not enhance the stimulatory effects obtained with each agent alone. The effects exerted by Ro 5-4864, PK 11195, and diazepam may be mediated via PBzS.
authors: Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
authors: E R
authors: ER
authors: Barnea
authors: F
authors: F
authors: Fares
authors: M
authors: M
authors: Gavish
mesh_terms: D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001667:Binding, Competitive; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011863:Radioimmunoassay
chemical_list: D001570:Benzodiazepinones; D007546:Isoquinolines; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D011374:Progesterone; D004958:Estradiol; C037850:PK 11195