title: Efficacy of proline in the treatment of menopause.
abstract: The amino acids in the placenta have multiple functions; however, the therapeutic effects of proline remain poorly for relief postmenopausal symptoms. The aim of present study was to evaluate the effects of proline in the treatment of menopause using in vitro and in vivo models. We assessed the therapeutic effects and regulatory mechanisms of proline by using MCF-7 estrogen-dependent cells, MG63 osteoblast cells, and ovariectomized mice model. An in vivo study was carried out in eight-week-old sham and ovariectomized group. The ovariectomized mouse was further subdivided into two groups administered orally with 17β-estradiol or proline (10 mg/kg/day) for eight weeks. Proline significantly increased cell proliferation and Ki-67 levels in MCF-7 cells and enhanced cell proliferation, alkaline phosphatase activity, extracellular signal-regulated kinase phosphorylation, and glutamyl-prolyl-tRNA synthetase activation in MG63 cells. The estrogen receptor-β and estrogen-response elements luciferase activity were significantly increased by proline in MCF-7 and MG63 cells. In ovariectomized mice, oral administration of proline (10 mg/kg/day) for eight weeks significantly reduced body and vaginal weights. Proline also significantly increased serum estradiol and alkaline phosphatase levels, whereas serum luteinizing hormone was decreased by proline. In addition, detailed microcomputed tomography analysis showed that the proline notably enhanced bone mineral density, trabecular bone volume, and trabecular number in ovariectomized mice. Those findings implied that proline can be a promising candidate for the treatment of menopause.
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Nam
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Myoung-Schook
authors.initials: MS
authors.lastname: Yoou
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea hmkim@khu.ac.kr.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam 336-795, Republic of Korea hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008593:Menopause; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D011392:Proline / Q000008:administration & dosage* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D011392:Proline
keywords: MCF-7 cells; MG-63 cells; Proline; estradiol; estrogen receptor; menopause
references.citation: Implant Dent. 2004 Mar;13(1):79-87
references.pmid: 15017309
references.citation: Acta Pharmacol Sin. 2001 Dec;22(12):1113-6
references.pmid: 11749810
references.citation: J Int Soc Sports Nutr. 2014 Dec 14;11(1):61
references.pmid: 25530736
references.citation: J Clin Densitom. 2003 Fall;6(3):251-8
references.pmid: 14514995
references.citation: JAMA. 1991 Apr 17;265(15):1985-90
references.pmid: 1826136
references.citation: J Ethnopharmacol. 2002 Feb;79(2):143-8
references.pmid: 11801374
references.citation: Climacteric. 2014 Oct;17(5):540-56
references.pmid: 24969415
references.citation: J Bone Miner Res. 1998 May;13(5):763-73
references.pmid: 9610739
references.citation: Eur J Pharmacol. 2012 Feb 15;676(1-3):26-33
references.pmid: 22192930
references.citation: Rev Endocr Metab Disord. 2010 Dec;11(4):229-36
references.pmid: 19798582
references.citation: J Bone Miner Res. 2016 Feb;31(2):326-35
references.pmid: 26334651
references.citation: Gynecol Endocrinol. 2006 Oct;22(10):578-84
references.pmid: 17135037
references.citation: Lancet. 2008 Mar 1;371(9614):760-70
references.pmid: 18313505
references.citation: Environ Health Perspect. 2007 Dec;115 Suppl 1:62-8
references.pmid: 18174952
references.citation: Biomed Pharmacother. 2002 Dec;56(10):492-7
references.pmid: 12504270
references.citation: Hum Reprod. 2015 Apr;30(4):848-52
references.pmid: 25662809
references.citation: BMC Complement Altern Med. 2010 Dec 31;10:82
references.pmid: 21194469
references.citation: J Ginseng Res. 2012 Apr;36(2):169-75
references.pmid: 23717117
references.citation: J Med Food. 2016 Jan;19(1):1-14
references.pmid: 26670451
references.citation: J Biomed Sci. 2014 Apr 17;21:30
references.pmid: 24742230
references.citation: Int Immunopharmacol. 2013 Aug;16(4):414-23
references.pmid: 23685128
references.citation: Nutr Res. 2014 Jun;34(6):467-77
references.pmid: 25026913
references.citation: Ecol Food Nutr. 2010 Nov-Dec;49(6):467-84
references.pmid: 21888574
references.citation: J Br Menopause Soc. 2005 Jun;11(2):61-5
references.pmid: 15970017
references.citation: Amino Acids. 2011 Apr;40(4):1053-63
references.pmid: 20697752
references.citation: J Biol Chem. 2001 Oct 12;276(41):38272-9
references.pmid: 11481323
references.citation: Proc Soc Exp Biol Med. 1985 Dec;180(3):468-73
references.pmid: 3909158
references.citation: Nat Commun. 2014 Aug 21;5:4708
references.pmid: 25144627
references.citation: Menopause Int. 2013 Jun;19(2):59-68
references.pmid: 23761319
references.citation: Brain Res Rev. 2008 Mar;57(2):470-80
references.pmid: 17850878
references.citation: J Cell Physiol. 2008 May;215(2):442-51
references.pmid: 17960591
references.citation: Nutrition. 2013 Nov-Dec;29(11-12):1381-7
references.pmid: 24035056
references.citation: Bull N Y Acad Med. 1979 Jun;55(6):591-9
references.pmid: 111747
references.citation: J Pharm Biomed Anal. 2004 Mar 10;34(5):1091-8
references.pmid: 15019043
references.citation: Ann Intern Med. 1995 Mar 15;122(6):430-3
references.pmid: 7856991
references.citation: J Ethnopharmacol. 2004 May;92(1):93-101
references.pmid: 15099854