G protein-coupled receptor 48 upregulates estrogen receptor alpha expression via cAMP/PKA signaling in the male reproductive tract.
The epididymis and efferent ducts play major roles in sperm maturation, transport, concentration and storage by reabsorbing water, ions and proteins produced from seminiferous tubules. Gpr48-null male mice demonstrate reproductive tract defects and infertility. In the present study, we found that estrogen receptor alpha (ERalpha) was dramatically reduced in the epididymis and efferent ducts in Gpr48-null male mice. We further revealed that ERalpha could be upregulated by Gpr48 activation via the cAMP/PKA signaling pathway. Moreover, we identified a cAMP responsive element (Cre) motif located at -1307 to -1300 bp in the ERalpha promoter that is able to interact with Cre binding protein (Creb). In conclusion, Gpr48 participates in the development of the male epididymis and efferent ducts through regulation of ERalpha expression via the cAMP/PKA signaling pathway.
Li
Xiao-Ying
XY
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 RuiJin 2nd Road, Shanghai 200025, China.
Lu
Yan
Y
Sun
Hai-Yan
HY
Wang
Ji-Qiu
JQ
Yang
Jun
J
Zhang
Hui-Jie
HJ
Fan
Neng-Guang
NG
Xu
Jia
J
Jiang
Jing-Jing
JJ
Liu
Ru-Ya
RY
Li
Da-Li
DL
Liu
Ming-Yao
MY
Ning
Guang
G
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004822:Epididymis / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000097:blood; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D043562:Receptors, G-Protein-Coupled; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases