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 (P₄) and estradiol (E₂) 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 3β-hydroxysteroid dehydrogenase (3β-HSD) or P450-aromatase (CYP19), respectively. Calcitriol stimulated in a dose-dependant manner E₂ and P₄ secretion. The use of a selective inhibitor of PKA prevented the effects of calcitriol upon E₂ secretion, but not on P₄. These results show that calcitriol is a physiological regulator of placental E₂ and P₄ production and suggest a novel role for calcitriol upon placental steroidogenesis.