The role of the G protein-coupled receptor GPR30 in the effects of estrogen in ovariectomized mice.
Artikel i vetenskaplig tidskrift, 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

Författare

Sara H Windahl

Göteborgs universitet

Niklas Andersson

Göteborgs universitet

A S Chagin

U E A Mårtensson

Catharina Lindholm

Göteborgs universitet

B Olde

Charlotte Swanson

Göteborgs universitet

Sofia Movérare-Skrtic

Göteborgs universitet

L Sävendahl

Jerker Fick

Göteborgs universitet

L M F Leeb-Lundberg

Claes Ohlsson

Göteborgs universitet

American Journal of Physiology - Endocrinology and Metabolism

0193-1849 (ISSN) 1522-1555 (eISSN)

Vol. 296 3 E490-6

Ämneskategorier

Endokrinologi och diabetes

DOI

10.1152/ajpendo.90691.2008

PubMed

19088255