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Evidence for a role of prolactin in calcium homeostasis: regulation of intestinal transient receptor potential vanilloid type 6, intestinal calcium absorption, and the 25-hydroxyvitamin D(3) 1alpha hydroxylase gene by prolactin Ajibade DV; Dhawan P; Fechner AJ; Meyer MB; Pike JW; Christakos SEndocrinology 2010[Jul]; 151 (7): 2974-84Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)(2)D(3), prolactin, or prolactin + 1,25(OH)(2)D(3). Prolactin alone (1 microg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D(9k). Combined treatment with 1,25(OH)(2)D(3) and prolactin resulted in an enhancement of the 1,25(OH)(2)D(3) induction of duodenal TRPV6 mRNA, calbindin-D(9k) mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)(2)D(3) alone]. Because lactation is associated with an increase in circulating 1,25(OH)(2)D(3), experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D(3) 1alpha hydroxylase [1alpha(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1alpha(OH)ase promoter -1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1alpha(OH)ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1alpha(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)(2)D(3) in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis.|25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*genetics[MESH]|Animals[MESH]|Blotting, Northern[MESH]|Blotting, Western[MESH]|Calbindins[MESH]|Calcifediol/pharmacology[MESH]|Calcium Channels/*genetics[MESH]|Calcium/blood/*metabolism[MESH]|Cell Line[MESH]|Electrophoretic Mobility Shift Assay[MESH]|Intestinal Absorption/*drug effects[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Mutagenesis, Site-Directed[MESH]|Prolactin/*pharmacology[MESH]|Receptors, Prolactin/genetics[MESH]|Reverse Transcriptase Polymerase Chain Reaction[MESH]|S100 Calcium Binding Protein G/genetics[MESH]|STAT5 Transcription Factor[MESH]|TRPV Cation Channels/*genetics[MESH] |
