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Effects of the selective GPER1 agonist G1 on bone growth

Journal article
Authors M. Iravani
Marie Lagerquist
E. Karimian
A. S. Chagin
Claes Ohlsson
L. Savendahl
Published in Endocrine Connections
Volume 8
Issue 9
Pages 1302-1309
ISSN 2049-3614
Publication year 2019
Published at Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 1302-1309
Language en
Keywords growth plate, growth, chondrocytes, estrogen, GPER1, G1, bone, estrogen-receptor-alpha, gpr30, expression, cancer, plate, 17-beta-estradiol, differentiation, activation, hormone, nuclear
Subject categories Cancer and Oncology, Endocrinology and Diabetes


Estrogens may affect bone growth locally or systemically via the known estrogen receptors ESR1, ESR2 and G protein-coupled estrogen receptor 1 (GPER1). Mouse and human growth plate chondrocytes have been demonstrated to express GPER1 and ablation of this receptor increased bone length in mice. Therefore, GPER1 is an attractive target for therapeutic modulation of bone growth, which has never been explored. To investigate the effects of activated GPER1 on the growth plate, we locally exposed mouse metatarsal bones to different concentrations of the selective GPER1 agonist G1 for 14 days ex vivo. The results showed that none of the concentrations of G1 had any direct effect on metatarsal bone growth when compared to control. To evaluate if GPER1 stimulation may systemically modulate bone growth, ovariectomized C57BL/6 mice were treated with G1 or beta-estradiol (E2). Similarly, G1 did not influence tibia and femur growth in treated mice. As expected, E2 treatment suppressed bone growth in vivo. We conclude that ligand stimulation of GPER1 does not influence bone growth in mice.

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