Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause

Amino Acids. 2016 Mar;48(3):791-800. doi: 10.1007/s00726-015-2127-6. Epub 2015 Nov 12.


Recently, the placenta mesotherapy has been widely used to treat menopause. Placenta contains amino acids, peptides, minerals, and estrogen. Here, we investigated the estrogen-like osteoprotective effects of glycine (a main ingredient of placenta) in in vitro and in vivo models of menopause. We assessed the effect of glycine on MG-63 osteoblast cell line, MCF-7 estrogen-dependent cell line, and ovariectomized (OVX) mice. Glycine significantly increased the MG-63 cell proliferation in a dose-dependent manner. Activity of alkaline phosphatase (ALP) and phosphorylation of extracellular-signal-regulated kinase were increased by glycine in MG-63 cells. Glycine also increased the BrdU-incorporation and Ki-67 mRNA expression in MCF-7 cells. Glycine induced the up-regulation of estrogen receptor-β mRNA expression and estrogen-response element-luciferase activity in MG-63 and MCF-7 cells. In OVX mice, glycine was administered orally at a daily dose of 10 mg/kg per day for 8 weeks. Glycine resulted in the greatest decrease in weight gain caused by ovariectomy. Meanwhile, vaginal weight reduced by ovariectomy was increased by glycine. Glycine significantly increased the ALP activity in OVX mice. MicroCT-analysis showed that glycine significantly enhanced bone mineral density, trabecular number, and connectivity density in OVX mice. Moreover, glycine significantly increased the serum 17β-estradiol levels reduced by ovariectomy. Glycine has an estrogen-like osteoprotective effect in menopause models. Therefore, we suggest that glycine may be useful for the treatment of menopause.

Keywords: 17β-Estradiol; Alkaline phosphatase; Bone mineral density; Glycine; Menopause; Ovariectomy.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism
  • Estrogens / administration & dosage*
  • Female
  • Glycine / administration & dosage*
  • Humans
  • Menopause / drug effects*
  • Menopause / genetics
  • Menopause / physiology
  • Mice
  • Mice, Inbred BALB C
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Weight Gain


  • Estrogen Receptor beta
  • Estrogens
  • Alkaline Phosphatase
  • Glycine