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 D3 1α Hydroxylase Gene by Prolactin

Increased 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 mu g/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-D9k 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 1 alpha hydroxylase [1 alpha(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1 alpha(OH)ase promoter -1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1 alpha(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 1 alpha(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. (Endocrinology 151: 2974-2984, 2010)