Abstract
BackgroundIn pregnancy, maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus. Considering that placenta is a site for vitamin D activation, and the versatility and potency of calcitriol, it is feasible that this hormone participates in fetal/placental development and physiology. In the present work we studied calcitriol actions upon human chorionic gonadotropin (hCG) secretion and expression in cultured trophoblasts, as well as vitamin D receptor (VDR) and CYP27B1 immunolocalization in placental villi.MethodsQuantification of hCG in culture media was performed by immunoassay. Expression studies were carried out by real time PCR. Analysis of CYP27B1 and VDR localization in placental slides were performed by immunohistochemistry. Statistical significance was established by one way ANOVA using Tukey test for comparisons.ResultsCalcitriol regulated hCG in a time-dependent manner: at 6 h the secosteroid stimulated hCG, whereas longer incubations (24 h) showed opposite effects. Interestingly, calcitriol stimulatory effects on hCG were accompanied by an increase in intracellular cAMP content and were abolished by pre-incubation of the cells with a selective protein kinase A inhibitor. Immunohistochemical techniques showed differential VDR localization in the syncytiotrophoblast layer or in the vascular smooth muscle cells depending on the epitope to which the antibodies were raised (specific for the carboxy- or amino-terminal regions, respectively). CYP27B1 was immunolocalized in the syncytiotrophoblast layer of placental villi.ConclusionThe presence and location of the vitamin D activating enzyme CYP27B1 as well as the specific receptor for vitamin D were shown in placental sections. The latter, together with findings demonstrating specific effects of calcitriol acting through the VDR and the cAMP/PKA signaling pathway upon hCG expression and secretion, indicate that there is a functional vitamin D endocrine system in the placenta, and recognize calcitriol as an autocrine regulator of hCG.
Highlights
In pregnancy, maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus
Regarding other molecules that are regulated by calcitriol in the placenta, Evans et al showed that calcitriol acts in an autocrine/paracrine fashion to regulate both acquired and innate immune responses, decreasing synthesis of cytokines such as granulocytemacrophage colony stimulating factor 2, tumor necrosis factor, and interleukin 6, but increasing expression of mRNA for the cathelicidin antimicrobial peptide [8]
Since human chorionic gonadotropin is a pivotal hormone for pregnancy maintenance, the aim of the present work was to broaden the knowledge of calcitriol actions in the placenta, focusing in the study of its effects upon hCG expression and secretion in cultured human syncytiotrophoblasts
Summary
Maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus. In the present work we studied calcitriol actions upon human chorionic gonadotropin (hCG) secretion and expression in cultured trophoblasts, as well as vitamin D receptor (VDR) and CYP27B1 immunolocalization in placental villi. Vitamin D is metabolized to the steroid hormone 1,25dihydroxyvitamin D3 or calcitriol, which regulates calcium homeostasis, modulates the immune response, and promotes cellular differentiation, among other actions. Calcitriol regulates placental lactogen expression as well as progesterone and estradiol secretion in cultured human syncytiotrophoblasts [6,7]. Since human chorionic gonadotropin (hCG) is a pivotal hormone for pregnancy maintenance, the aim of the present work was to broaden the knowledge of calcitriol actions in the placenta, focusing in the study of its effects upon hCG expression and secretion in cultured human syncytiotrophoblasts. The data presented display a functional vitamin D endocrine system present in human placenta and suggest its involvement in regulating placental physiology
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