title: Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol.
abstract: Calcitriol exerts a diverse range of biological actions including the control of growth and cell differentiation, modulation of hormone secretion, and regulation of reproductive function. The placenta synthesizes calcitriol through the expression of CYP27B1, but little is known about local actions of this hormone in the fetoplacental unit. The objective of this study was to investigate the effects of calcitriol upon progesterone (P(4)) and estradiol (E(2)) secretion in trophoblasts cultured from term human placenta. Cells were incubated in the presence of calcitriol for 18 h and pregnenolone or androstenedione were subsequently added as substrates for the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or P450-aromatase (CYP19), respectively. Calcitriol stimulated in a dose-dependent manner E(2) and P(4) secretion. The use of a selective inhibitor of PKA prevented the effects of calcitriol upon E(2) secretion, but not on P(4). These results show that calcitriol is a physiological regulator of placental E(2) and P(4) production and suggest a novel role for calcitriol upon placental steroidogenesis.
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan 14000, México, D.F., Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.forename: Euclides
authors.initials: E
authors.lastname: Avila
authors.forename: Guillermo
authors.initials: G
authors.lastname: Hernández
authors.forename: Ali
authors.initials: A
authors.lastname: Halhali
authors.forename: Benjamín
authors.initials: B
authors.lastname: Biruete
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000096:biosynthesis*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D013449:Sulfonamides / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism
chemical_list: D007546:Isoquinolines; D013449:Sulfonamides; D011374:Progesterone; D004958:Estradiol; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D002117:Calcitriol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide