Background: Abnormal growth is a common problem in children. Some children do not respond to growth hormone therapy and alternative treatments selectively targeting the growth plate are needed. High doses of estrogens induce growth plate closure and stop further growth. However, high-dose estrogen treatment may also have severe side effects, including increased risk of cancer and reduced fertility. The expression of estrogen receptors (ER), including GPER-1, has been demonstrated in growth plate cartilage in humans as well as mice.
Objective and hypotheses: We hypothesized that GPER-1 mediates estrogenic effects on growth plate cartilage.
Method: Murine postnatal metatarsal bones were cultured with 1, 10, 100 and 300 nM of the selective GPER-1 agonist G1 for 2 weeks. Moreover, 12-week old ovariectomized female C57BL/6 mice were treated with daily subcutaneous injections of G1 at 0.2 mg/kg body weight for 4 weeks. Lengths of metatarsal bones, tibiae, and femur were measured and growth plate morphology was analyzed. The effects of G1 on chondrocyte proliferation in cultured metatarsal bones were analyzed by PCNA staining.
Results: In G1 treated cultured metatarsal bones, resting and proliferative zone heights were increased when compared to control bones. Furthermore, chondrocyte proliferation was also increased in the metatarsal bones cultured with G1. However, when measuring bone length this was not significantly affected when exposed to G1 in vitro as well as in vivo.
Conclusion: Our data suggest that estrogen may affect the growth plate via GPER-1 mainly by increasing chondrocyte proliferation and proliferative zone height. To clarify if this effect will translate into increased bone length, a longer treatment study would be needed.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology