title: 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.
abstract: 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 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Dare V
authors.initials: DV
authors.lastname: Ajibade
authors.forename: Puneet
authors.initials: P
authors.lastname: Dhawan
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Fechner
authors.forename: Mark B
authors.initials: MB
authors.lastname: Meyer
authors.forename: J Wesley
authors.initials: JW
authors.lastname: Pike
authors.forename: Sylvia
authors.initials: S
authors.lastname: Christakos
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D064026:Calbindins; D002112:Calcifediol / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics*; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D011388:Prolactin / Q000494:pharmacology*; D011981:Receptors, Prolactin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D050799:STAT5 Transcription Factor; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D064026:Calbindins; D015220:Calcium Channels; D011981:Receptors, Prolactin; D064030:S100 Calcium Binding Protein G; D050799:STAT5 Transcription Factor; D050916:TRPV Cation Channels; C446923:Trpv6 protein, mouse; D011388:Prolactin; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol; D002118:Calcium
references.citation: Clin Chem. 1967 Feb;13(2):101-14
references.pmid: 4959769
references.citation: Gene. 2002 Feb 20;285(1-2):1-24
references.pmid: 12039028
references.citation: J Biol Chem. 1989 Oct 15;264(29):17454-61
references.pmid: 2551904
references.citation: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E372-84
references.pmid: 17488805
references.citation: Science. 1979 Jun 29;204(4400):1427-9
references.pmid: 451573
references.citation: Crit Rev Biochem Mol Biol. 2001 Apr;36(2):107-260
references.pmid: 11370791
references.citation: J Nutr. 1995 Jul;125(7 Suppl):1971S-1979S
references.pmid: 7602379
references.citation: Diabetes. 2007 Jun;56(6):1623-9
references.pmid: 17360981
references.citation: Prostate. 2007 Oct 1;67(14):1498-506
references.pmid: 17680631
references.citation: Pflugers Arch. 2009 Sep;458(5):993-1005
references.pmid: 19449156
references.citation: Endocrinology. 2008 Jun;149(6):3196-205
references.pmid: 18325990
references.citation: Proc Natl Acad Sci U S A. 1979 Nov;76(11):5549-53
references.pmid: 293660
references.citation: Mol Endocrinol. 2002 Apr;16(4):774-84
references.pmid: 11923474
references.citation: J Bone Miner Res. 2003 Oct;18(10):1725-36
references.pmid: 14584880
references.citation: Am J Physiol. 1959 Feb;196(2):357-62
references.pmid: 13627180
references.citation: Mol Endocrinol. 2009 Aug;23(8):1242-54
references.pmid: 19423653
references.citation: Mol Endocrinol. 2006 Jun;20(6):1447-61
references.pmid: 16574738
references.citation: EMBO J. 1994 Sep 15;13(18):4361-9
references.pmid: 7925280
references.citation: J Biol Chem. 2005 Dec 9;280(49):40589-98
references.pmid: 16195230
references.citation: Mol Endocrinol. 1998 May;12(5):675-87
references.pmid: 9605930
references.citation: Am J Physiol. 1980 Jul;239(1):E64-8
references.pmid: 6249126
references.citation: Physiol Rev. 2005 Jan;85(1):373-422
references.pmid: 15618484
references.citation: Neuroendocrinology. 1992 Oct;56(4):561-5
references.pmid: 1475014
references.citation: J Biol Chem. 1987 Dec 5;262(34):16553-7
references.pmid: 2445747
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Mol Cell Biol. 2005 Jan;25(1):472-87
references.pmid: 15601867
references.citation: Arch Biochem Biophys. 1994 Jan;308(1):171-4
references.pmid: 8311449
references.citation: Arch Biochem Biophys. 2004 Dec 15;432(2):152-66
references.pmid: 15542054
references.citation: Endocrinology. 2003 Sep;144(9):3885-94
references.pmid: 12933662
references.citation: J Endocrinol. 1982 Sep;94(3):443-53
references.pmid: 6896886
references.citation: J Biol Chem. 1997 Mar 21;272(12):7567-9
references.pmid: 9119818
references.citation: Endocrinology. 1999 Jan;140(1):301-9
references.pmid: 9886839
references.citation: Recent Prog Horm Res. 1972;28:471-526
references.pmid: 4569231
references.citation: Biochim Biophys Acta. 1981 Jan 7;672(1):7-15
references.pmid: 6894254
references.citation: Endocrinology. 1993 May;132(5):2090-8
references.pmid: 8386606
references.citation: Endocrinology. 1981 Sep;109(3):900-7
references.pmid: 6894899
references.citation: J Biol Chem. 2009 Apr 24;284(17):11059-69
references.pmid: 19261615
references.citation: Clin Endocrinol (Oxf). 1987 Jun;26(6):667-74
references.pmid: 3665123
references.citation: J Biol Chem. 1972 Sep 10;247(17):5520-6
references.pmid: 4341346
references.citation: Endocr Rev. 1998 Jun;19(3):225-68
references.pmid: 9626554
references.citation: Cell. 1979 Aug;17(4):1013-23
references.pmid: 487427
references.citation: Nutr Rev. 2008 Oct;66(10 Suppl 2):S73-87
references.pmid: 18844850
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13572-6
references.pmid: 11698670
references.citation: Mol Endocrinol. 2001 Feb;15(2):228-40
references.pmid: 11158330
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8831-5
references.pmid: 7568026
references.citation: Am J Physiol. 1990 Oct;259(4 Pt 1):G631-8
references.pmid: 2221074
references.citation: J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):469-77
references.pmid: 1562518
references.citation: Endocrinology. 1980 Jul;107(1):81-4
references.pmid: 6892897
references.citation: Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E609-19
references.pmid: 19567804
references.citation: Mol Cell Biol. 2000 Jan;20(1):389-401
references.pmid: 10594041
references.citation: Arch Biochem Biophys. 2005 Jan 15;433(2):466-73
references.pmid: 15581603
references.citation: Am J Physiol. 1980 Nov;239(5):E322-7
references.pmid: 7435610
references.citation: Endocrinology. 2010 Mar;151(3):886-95
references.pmid: 20051486
references.citation: Life Sci. 1976 Dec 1;19(11):1751-6
references.pmid: 1004133
references.citation: Endocrinology. 1975 May;96(5):1165-70
references.pmid: 1168128
references.citation: Diabetes. 2005 Jul;54(7):1968-75
references.pmid: 15983196
references.citation: Can J Physiol Pharmacol. 2006 May;84(5):555-63
references.pmid: 16902601
references.citation: Mol Endocrinol. 2004 Jul;18(7):1670-86
references.pmid: 15071091
references.citation: Arch Biochem Biophys. 2001 Apr 1;388(1):121-6
references.pmid: 11361127
references.citation: Obstet Gynecol. 1990 Sep;76(3 Pt 2):485-9
references.pmid: 2381632
references.citation: Endocrinology. 1980 Feb;106(2):469-75
references.pmid: 7353522
references.citation: Can J Physiol Pharmacol. 2001 May;79(5):430-8
references.pmid: 11405247
references.citation: Science. 1981 Nov 27;214(4524):1038-9
references.pmid: 7302575
references.citation: Mol Biol Cell. 2008 May;19(5):1912-21
references.pmid: 18287530
references.citation: Can J Physiol Pharmacol. 2007 Jun;85(6):569-81
references.pmid: 17823618