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

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Abstract

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.

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Abbreviations

OVX mice:

Ovariectomized mice

ALP:

Alkaline phosphatase

ER:

Estrogen receptor

ERK:

Extracellular signal-regulated kinase

ERE:

Estrogen response element

FSH:

Follicle-stimulating hormone

LH:

Luteinizing hormone

MicroCT:

Microcomputed tomography

BMD:

Bone mineral density

Tb.N:

Trabecular number

Conn.D:

Connectivity density

References

  • Abdallah HM, Al-Abd AM, Asaad GF, Abdel-Naim AB, El-halawany AM (2014) Isolation of antiosteoporotic compounds from seeds of Sophora japonica. PLoS One 9:e98559

    Article  PubMed Central  PubMed  Google Scholar 

  • Ahn HN, Jeong SY, Bae GU, Chang M, Zhang D, Liu X et al (2014) Selective estrogen receptor modulation by Larrea nitida on MCF-7 cell proliferation and immature rat uterus. Biomol Ther (Seoul) 22:347–354

    Article  CAS  Google Scholar 

  • Auro K, Joensuu A, Fischer K, Kettunen J, Salo P, Mattsson H et al (2014) A metabolic view on menopause and ageing. Nat Commun 5:4708

    Article  CAS  PubMed  Google Scholar 

  • Bakhsh A, Mustapha NM, Mohamed S (2013) Catechin-rich oil palm leaf extract enhances bone calcium content of estrogen-deficient rats. Nutrition 29:667–672

    Article  CAS  PubMed  Google Scholar 

  • Burger HG, Hale GE, Robertson DM, Dennerstein L (2007) A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women’s Midlife Health Project. Hum Reprod Update 13:559–565

    Article  CAS  PubMed  Google Scholar 

  • Camporez JP, Akamine EH, Davel AP, Franci CR, Rossoni LV, Carvalho CR (2011) Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats. J Physiol 589:2585–2596

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Camporez JP, Jornayvaz FR, Lee HY, Kanda S, Guigni BA, Kahn M et al (2013) Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance. Endocrinology 154:1021–1028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Choi RC, Gao QT, Cheung AW, Zhu JT, Lau FT, Li J et al (2011) A Chinese herbal decoction, danggui buxue tang, stimulates proliferation, differentiation and gene expression of cultured osteosarcoma cells: genomic approach to reveal specific gene activation. Evid Based Complement Alternat Med 2011:307548

    PubMed Central  PubMed  Google Scholar 

  • Dall’Acqua S, Tomè F, Vitalini S, Agradi E, Innocenti G (2009) In vitro estrogenic activity of Asplenium trichomanes L. extracts and isolated compounds. J Ethnopharmacol 122:424–429

    Article  PubMed  Google Scholar 

  • Doyle BJ, Mahady GB (2007) Phytotherapies for menopause. Drugs Future 32:897–905

    Article  CAS  Google Scholar 

  • Doyle BJ, Frasor J, Bellows LE, Locklear TD, Perez A, Gomez-Laurito J et al (2009) Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms. Menopause 16:748–755

    Article  PubMed Central  PubMed  Google Scholar 

  • Fini M, Torricelli P, Giavaresi G, Carpi A, Nicolini A, Giardino R (2001) Effect of l-lysine and l-arginine on primary osteoblast cultures from normal and osteopenic rats. Biomed Pharmacother 55:213–220

    Article  CAS  PubMed  Google Scholar 

  • Fu SW, Zeng GF, Zong SH, Zhang ZY, Zou B, Fang Y et al (2014) Systematic review and meta-analysis of the bone protective effect of phytoestrogens on osteoporosis in ovariectomized rats. Nutr Res 34:467–477

    Article  CAS  PubMed  Google Scholar 

  • Gruber HE, Ivey JL, Baylink DJ, Matthews M, Nelp WB, Sisom K et al (1984) Long-term calcitonin therapy in postmenopausal osteoporosis. Metabolism 33:295–303

    Article  CAS  PubMed  Google Scholar 

  • Guay MP, Dragomir A, Pilon D, Moride Y, Perreault S (2007) Changes in pattern of use, clinical characteristics and persistence rate of hormone replacement therapy among postmenopausal women after the WHI publication. Pharmacoepidemiol Drug Saf 16:17–27

    Article  PubMed  Google Scholar 

  • Hyun H, Park H, Jeong J, Kim J, Kim H, Oh HI et al (2014) Effects of watercress containing rutin and rutin alone on the proliferation and osteogenic differentiation of human osteoblast-like MG-63 cells. Korean J Physiol Pharmacol 18:347–352

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ji M, Leem KH, Kim M, Kim HK (2007) Egg yolk soluble protein stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biosci Biotechnol Biochem 71:1327–1329

    Article  CAS  PubMed  Google Scholar 

  • Karimian E, Tamm C, Chagin AS, Samuelsson K, Kjartansdóttir KR, Ohlsson C et al (2013) Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits. PLoS One 8:e67859

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim DG, Navalgund AR, Tee BC, Noble GJ, Hart RT, Lee HR (2012) Increased variability of bone tissue mineral density resulting from estrogen deficiency influences creep behavior in a rat vertebral body. Bone 51:868–875

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim HK, Kim MG, Leem KH (2014a) Effects of egg yolk-derived peptide on osteogenic gene expression and MAPK activation. Molecules 19:12909–12924

    Article  PubMed  Google Scholar 

  • Kim MH, Choi YY, Han JM, Lee HS, Hong SB, Lee SG et al (2014b) Ameliorative effects of Schizandra chinensis on osteoporosis via activation of estrogen receptor (ER)-α/-β. Food Funct 5:1594–1601

    Article  CAS  PubMed  Google Scholar 

  • Kim MH, Jeong H, Park M, Moon PD (2014c) Effect of KH-BaRoKer-SeongJangTang based on traditional medicine theory on longitudinal bone growth. TANG 4:e14

    Google Scholar 

  • Lai CF, Chaudhary L, Fausto A, Halstead LR, Ory DS, Avioli LV et al (2001) Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells. J Biol Chem 276:14443–14450

    CAS  PubMed  Google Scholar 

  • Le Donne M, Caruso C, Mancuso A, Costa G, Iemmo R, Pizzimenti G et al (2011) The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause. Arch Gynecol Obstet 283:1319–1323

    Article  CAS  PubMed  Google Scholar 

  • Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR (2008) Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 32:949–958

    Article  CAS  Google Scholar 

  • Mahady GB, Huang Y, Doyle BJ, Locklear TD (2006) Black cohosh (Actaea racemosa) for the mitigation of menopausal symptoms: recent developments in clinical safety and efficacy. J Womens Health 2:773–784

    Google Scholar 

  • Melton LJ 3rd, Johnell O, Lau E, Mautalen CA, Seeman E (2004) Osteoporosis and the global competition for health care resources. J Bone Miner Res 19:1055–1058

    Article  PubMed  Google Scholar 

  • Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R et al (2013) D538G mutation in estrogen receptor-α: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res 73:6856–6864

    Article  CAS  PubMed  Google Scholar 

  • Mishra R, Bhadauria S, Murthy PK, Murthy PS (2011) Glycine soya diet synergistically enhances the suppressive effect of tamoxifen and inhibits tamoxifen-promoted hepatocarcinogenesis in 7,12-dimethylbenz[α]anthracene-induced rat mammary tumor model. Food Chem Toxicol 49:434–440

    Article  CAS  PubMed  Google Scholar 

  • Moon PD, Kim KY, Rew KH, Kim HM, Jeong HJ (2014) Anti-fatigue effects of porcine placenta and its amino acids in a behavioral test on mice. Can J Physiol Pharmacol 92:937–944

    Article  CAS  PubMed  Google Scholar 

  • Parazzini F (2015) Resveratrol, tryptophanum, glycine and vitamin E: a nutraceutical approach to sleep disturbance and irritability in peri- and post-menopause. Minerva Ginecol 67:1–5

    CAS  PubMed  Google Scholar 

  • Qiraouani Boucetta K, Charrouf Z, Aguenaou H, Derouiche A, Bensouda Y (2015) The effect of dietary and/or cosmetic argan oil on postmenopausal skin elasticity. Clin Interv Aging 10:339–349

    PubMed Central  PubMed  Google Scholar 

  • Rogers NH, Perfield JW 2nd, Strissel KJ, Obin MS, Greenberg AS (2009) Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology 150:2161–2168

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Saunders PT, Maguire SM, Gaughan J, Millar MR (1997) Expression of oestrogen receptor beta (ER beta) in multiple rat tissues visualised by immunohistochemistry. J Endocrinol 154:13–16

    Article  Google Scholar 

  • Shimatsu A, Tai S, Imori M, Ihara K, Taketsuna M, Funai J et al (2013) Efficacy and safety of growth hormone replacement therapy in Japanese adults with growth hormone deficiency: a post-marketing observational study. Endocr J 60:1131–1144

    Article  CAS  PubMed  Google Scholar 

  • Shughure PJ, Lane MV, Scrimo PJ, Merchenthaler I (1998) Comparative distribution of estrogen receptor-alpha (ER-alpha) and beta (ER-beta) mRNA in the rat pituitary, gonad, and reproductive tract. Steroids 63:498–504

    Article  Google Scholar 

  • Smith CL, O’Malley BW (2004) Coregulator function: a key to understanding tissue specifi city of selective receptor modulators. Endocr Rev 25:45–71

    Article  CAS  PubMed  Google Scholar 

  • Stossi F, Barnett DH, Frasor J, Komm B, Lyttle CR, Katzenellenbogen BS (2004) Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteosarcoma cells: distinct and common target genes for these receptors. Endocrinology 145:3473–3486

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Ding J, Ma XP, Ma YH, Liu ZQ, Lin N (2014) Treatment with Panax ginseng antagonizes the estrogen decline in ovariectomized mice. Int J Mol Sci 15:7827–7840

    Article  PubMed Central  PubMed  Google Scholar 

Download references

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Correspondence to Hyun-Ja Jeong.

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Kim, MH., Kim, HM. & Jeong, HJ. Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause. Amino Acids 48, 791–800 (2016). https://doi.org/10.1007/s00726-015-2127-6

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