GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice.
Estrogen regulation of the male skeleton was first clearly demonstrated in patients with aromatase deficiency or a mutation in the ERα gene. Estrogen action on the skeleton is thought to occur mainly through the action of the nuclear receptors ERα and ERβ. Recently, in vitro studies have shown that the G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). GPR30-deficient mouse models have been generated to study the in vivo function of this protein; however, its in vivo role in the male skeleton remains underexplored. We have characterized size, body composition, and bone mass in adult male Gpr30 knockout (KO) mice and their wild-type (WT) littermates. Gpr30 KO mice weighed more and had greater nasal-anal length (p < .001). Both lean mass and percent body fat were increased in the KO mice. Femur length was greater in Gpr30 KO mice, as was whole-body, spine, and femoral areal bone mineral density (p < .01). Gpr30 KO mice showed increased trabecular bone volume (p < .01) and cortical thickness (p < .001). Mineralized surface was increased in Gpr30 KO mice (p < .05). Bromodeoxyuridine (BrdU) labeling showed greater proliferation in the growth plate of Gpr30 KO mice (p < .05). Under osteogenic culture conditions, Gpr30 KO femoral bone marrow cells produced fewer alkaline phosphatase-positive colonies in early differentiating osteoblast cultures but showed increased mineralized nodule deposition in mature osteoblast cultures. Serum insulin-like growth factor 1 (IGF-1) levels were not different. These data suggest that in male mice, GPR30 action contributes to regulation of bone mass, size, and microarchitecture by a mechanism that does not require changes in circulating IGF-1.
Ford
Jeffery
J
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9058, USA.
Hajibeigi
Asghar
A
Long
Michael
M
Hahner
Lisa
L
Gore
Crystal
C
Hsieh
Jer-Tseng
JT
Clegg
Deborah
D
Zerwekh
Joseph
J
Oz
Orhan K
OK
D015502:Absorptiometry, Photon / Q000379:methods; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D003720:Densitometry / Q000379:methods; D004967:Estrogens / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics*
D004967:Estrogens; C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase; D001973:Bromodeoxyuridine