The role of the G protein-coupled receptor GPR30 in the effects of estrogen in ovariectomized mice.
Journal article, 2009
In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). The aim of the present study was to determine the possible in vivo role of GPR30 as a functional ER primarily for the regulation of skeletal parameters, including bone mass and longitudinal bone growth, but also for some other well-known estrogen-regulated parameters, including uterine weight, thymus weight, and fat mass. Three-month-old ovariectomized (OVX) GPR30-deficient mice (GPR30(-/-)) and wild-type (WT) mice were treated with either vehicle or increasing doses of estradiol (E(2); 0, 30, 70, 160, or 830 ng.mouse(-1).day(-1)). Body composition [bone mineral density (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry, while the cortical and trabecular bone compartments were analyzed by peripheral quantitative computerized tomography. Quantitative histological analyses were performed in the distal femur growth plate. Bone marrow cellularity and distribution were analyzed using a fluorescence-activated cell sorter. The estrogenic responses on most of the investigated parameters, including increase in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and increase in bone marrow cellularity, were similar for all of the investigated E(2) doses in WT and GPR30(-/-) mice. On the other hand, E(2) treatment reduced longitudinal bone growth, reflected by decreased femur length and distal femur growth plate height, in the WT mice but not in the GPR30(-/-) mice compared with vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not required for normal estrogenic responses on several major well-known estrogen-regulated parameters. In contrast, GPR30 is required for a normal estrogenic response in the growth plate.
Estrogen
Estrogens
Femur
Organ Size
Thymus Gland
growth & development
Mice
Bone Development
Growth Plate
cytology
Adipose Tissue
Mice
cytology
anatomy & histology
metabolism
metabolism
Uterus
Animals
Bone Density
genetics
Mutant Strains
growth & development
Female
growth & development
anatomy & histology
growth & development
Receptors
physiology
anatomy & histology
G-Protein-Coupled
growth & development
Ovariectomy
metabolism
Receptors
Author
Sara H Windahl
University of Gothenburg
Niklas Andersson
University of Gothenburg
A S Chagin
U E A Mårtensson
Catharina Lindholm
University of Gothenburg
B Olde
Charlotte Swanson
University of Gothenburg
Sofia Movérare-Skrtic
University of Gothenburg
L Sävendahl
Jerker Fick
University of Gothenburg
L M F Leeb-Lundberg
Claes Ohlsson
University of Gothenburg
American Journal of Physiology - Endocrinology and Metabolism
0193-1849 (ISSN) 1522-1555 (eISSN)
Vol. 296 3 E490-6Subject Categories
Endocrinology and Diabetes
DOI
10.1152/ajpendo.90691.2008
PubMed
19088255