Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol.
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.
Barrera
David
D
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.
Avila
Euclides
E
Hernández
Guillermo
G
Halhali
Ali
A
Biruete
Benjamín
B
Larrea
Fernando
F
Díaz
Lorenza
L
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
D007546:Isoquinolines; D013449:Sulfonamides; D011374:Progesterone; D004958:Estradiol; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D002117:Calcitriol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide