| dc.description.abstract | Prolactin is a protein hormone that is produced by the pituitary lactotrophs and also
by extrapituitary sites such as decidua and lymphocytes. Calcitriol, the active form
of vitamin D3, is a secosteroid with immunomodulatory actions that exerts its
effects through vitamin D receptor (VDR). It is known that calcitriol stimulates PRL
expression in pituitary cells in culture as well as in decidua. However, regulators of
lymphocyte prolactin synthesis are less known. The aim of this study was to
evaluate the effect of calcitriol on the mRNA expression and secretion of PRL in
cultured peripheral blood mononuclear cells (PBMNC) from healthy subjects.
PBMNC were cultured with different concentrations of calcitriol in the absence or
presence of a VDR antagonist. The presence of VDR was evaluated by Westernblot.
PRL, and highly responsive genes for calcitriol such as VDR, CYP24A1 and
CYP27B1 mRNA expression were evaluated by RT and real time PCR. PRL
secretion was quantified by ELISA and protein-VDRE binding was assessed by
EMSA. Immunoblots showed the presence of a 48-kDa VDR form in PHA treated
PBMNC and Jurkat cells, while a 75-kDa form was recognized in both, nonactivated
and activated cells. Treatment with calcitriol increased both, PRL and
CYP24A1 mRNA expression only in non-activated cells, in a dose-dependent
manner. Incubation with VDR antagonist reverted the stimulatory effect of calcitriol
upon PRL expression. In activated cells, calcitriol increased CYP27B1 and VDR
expression. EMSA analysis showed that lysates of non-activated cells contained a
protein that binds to VDRE. In conclusion, calcitriol stimulates PRL and CYP24A1
gene expression in non-activated lymphocytes through a VDR-mediated
mechanism. This study provides evidence that calcitriol exerts differential effects
depending on activation cellular state which could be related to the presence of
functional VDR isoforms in lymphocytes. | |
