Accelerated Mammary Gland Development during Pregnancy and Delayed Postlactational Involution in Vitamin D3 Receptor Null Mice Export

@article{citeulike:5894434, abstract = {The vitamin D receptor (VDR) is present in mammary gland, and VDR ablation is associated with accelerated glandular development during puberty. VDR is a nuclear receptor whose ligand, 1,25-dihydroxyvitamin D [1,25-(OH)2D] is generated after metabolic activation of vitamin D by specific vitamin D hydroxylases. In these studies, we demonstrate that both the VDR and the vitamin D 1-{alpha} hydroxylase (CYP27B1), which produces 1,25-(OH)2D are present in mammary gland and dynamically regulated during pregnancy, lactation, and involution. Furthermore, we show that mice lacking VDR exhibit accelerated lobuloalveolar development and premature casein expression during pregnancy and delayed postlactational involution compared with mice with functional VDR. The delay in mammary gland regression after weaning of VDR knockout mice is associated with impaired apoptosis as demonstrated by reductions in terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling staining, caspase-3 activation and Bax induction. Under the conditions used in this study, VDR ablation was not associated with hypocalcemia, suggesting that altered mammary gland development in the absence of the VDR is not related to disturbances in calcium homeostasis. Furthermore, in the setting of normocalcemia, VDR ablation does not affect milk protein or calcium content. These studies suggest that the VDR contributes to mammary cell turnover during the reproductive cycle, and its effects may be mediated via both endocrine and autocrine signaling pathways. Unlike many mammary regulatory factors that exert transient, stage-specific effects, VDR signaling impacts on mammary gland biology during all phases of the reproductive cycle. 10.1210/me.2003-0469}, author = {Zinser, Glendon M. and Welsh, JoEllen}, citeulike-article-id = {5894434}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/me.2003-0469}, citeulike-linkout-1 = {http://mend.endojournals.org/content/18/9/2208.abstract}, citeulike-linkout-2 = {http://mend.endojournals.org/content/18/9/2208.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15178742}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15178742}, day = {1}, doi = {10.1210/me.2003-0469}, journal = {Mol Endocrinol}, keywords = {breast, for:songpku, involution, pregnancy, vitd}, month = {September}, number = {9}, pages = {2208--2223}, posted-at = {2009-10-06 03:01:14}, priority = {2}, title = {Accelerated Mammary Gland Development during Pregnancy and Delayed Postlactational Involution in Vitamin D3 Receptor Null Mice}, url = {http://dx.doi.org/10.1210/me.2003-0469}, volume = {18}, year = {2004} }

TY - JOUR ID - citeulike:5894434 L3 - citeulike-article-id:5894434 N2 - The vitamin D receptor (VDR) is present in mammary gland, and VDR ablation is associated with accelerated glandular development during puberty. VDR is a nuclear receptor whose ligand, 1,25-dihydroxyvitamin D [1,25-(OH)2D] is generated after metabolic activation of vitamin D by specific vitamin D hydroxylases. In these studies, we demonstrate that both the VDR and the vitamin D 1-{alpha} hydroxylase (CYP27B1), which produces 1,25-(OH)2D are present in mammary gland and dynamically regulated during pregnancy, lactation, and involution. Furthermore, we show that mice lacking VDR exhibit accelerated lobuloalveolar development and premature casein expression during pregnancy and delayed postlactational involution compared with mice with functional VDR. The delay in mammary gland regression after weaning of VDR knockout mice is associated with impaired apoptosis as demonstrated by reductions in terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling staining, caspase-3 activation and Bax induction. Under the conditions used in this study, VDR ablation was not associated with hypocalcemia, suggesting that altered mammary gland development in the absence of the VDR is not related to disturbances in calcium homeostasis. Furthermore, in the setting of normocalcemia, VDR ablation does not affect milk protein or calcium content. These studies suggest that the VDR contributes to mammary cell turnover during the reproductive cycle, and its effects may be mediated via both endocrine and autocrine signaling pathways. Unlike many mammary regulatory factors that exert transient, stage-specific effects, VDR signaling impacts on mammary gland biology during all phases of the reproductive cycle. 10.1210/me.2003-0469 IS - 9 JF - Mol Endocrinol EP - 2223 TI - Accelerated Mammary Gland Development during Pregnancy and Delayed Postlactational Involution in Vitamin D3 Receptor Null Mice VL - 18 SP - 2208 KW - breast KW - for:songpku KW - involution KW - pregnancy KW - vitd AU - Zinser, Glendon AU - Welsh, JoEllen PY - 2004/09/01/ UR - http://dx.doi.org/10.1210/me.2003-0469 ER -