Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 May;149(5):2383-90.
doi: 10.1210/en.2007-1247. Epub 2008 Feb 14.

Bone growth and turnover in progesterone receptor knockout mice

David J Rickard  1 , Urszula T Iwaniec, Glenda Evans, Theresa E Hefferan, Jamie C Hunter, Katrina M Waters, John P Lydon, Bert W O'Malley, Sundeep Khosla, Thomas C Spelsberg, Russell T Turner
Affiliations

Bone growth and turnover in progesterone receptor knockout mice

David J Rickard et al. Endocrinology. 2008 May.

Abstract

The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Total body weights (A), uterine wet weights (B), and proximal tibia longitudinal growth rates (C) of WT and PRKO mice measured at 6, 12, and 26 wk of age. Ablation of PR signaling had no effect on body weight gain, uterine weight gain, or the age-related slowing of bone growth. Longitudinal growth rate was below the limit of detection in 26-wk-old mice of either genotype (<5 μm/d). Values are mean ± se. a, Significantly different from WT at 6 wk; b, significantly different from PRKO at 6 wk; c, significantly different from WT at 12 wk; d, significantly different from PRKO at 12 wk; P < 0.01.
Figure 2
Figure 2
Cancellous bone architecture at the proximal tibia epiphysis as a function of age in WT and PRKO mice. Values are mean ± se. a, Significantly different from WT at 6 wk; b, significantly different from PRKO at 6 wk; *, significantly different from age-matched WT; P < 0.01.
Figure 3
Figure 3
Cancellous bone architecture and dynamic histomorphometry at the proximal tibia metaphysis as a function of age in WT and PRKO mice. Values are mean ± se. a, Significantly different from WT at 12 wk; b, significantly different from PRKO at 12 wk; *, significantly different from age-matched WT; P < 0.01.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.
    Heijmans J, Muncan V, Jacobs RJ, de Jonge-Muller ES, Graven L, Biemond I, Ederveen AG, Groothuis PG, Mosselman S, Hardwick JC, Hommes DW, van den Brink GR. Heijmans J, et al. PLoS One. 2011;6(7):e22620. doi: 10.1371/journal.pone.0022620. Epub 2011 Jul 27. PLoS One. 2011. PMID: 21818351 Free PMC article.
  • Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.
    Tachmazidou I, Süveges D, Min JL, Ritchie GRS, Steinberg J, Walter K, Iotchkova V, Schwartzentruber J, Huang J, Memari Y, McCarthy S, Crawford AA, Bombieri C, Cocca M, Farmaki AE, Gaunt TR, Jousilahti P, Kooijman MN, Lehne B, Malerba G, Männistö S, Matchan A, Medina-Gomez C, Metrustry SJ, Nag A, Ntalla I, Paternoster L, Rayner NW, Sala C, Scott WR, Shihab HA, Southam L, St Pourcain B, Traglia M, Trajanoska K, Zaza G, Zhang W, Artigas MS, Bansal N, Benn M, Chen Z, Danecek P, Lin WY, Locke A, Luan J, Manning AK, Mulas A, Sidore C, Tybjaerg-Hansen A, Varbo A, Zoledziewska M, Finan C, Hatzikotoulas K, Hendricks AE, Kemp JP, Moayyeri A, Panoutsopoulou K, Szpak M, Wilson SG, Boehnke M, Cucca F, Di Angelantonio E, Langenberg C, Lindgren C, McCarthy MI, Morris AP, Nordestgaard BG, Scott RA, Tobin MD, Wareham NJ; SpiroMeta Consortium; GoT2D Consortium; Burton P, Chambers JC, Smith GD, Dedoussis G, Felix JF, Franco OH, Gambaro G, Gasparini P, Hammond CJ, Hofman A, Jaddoe VWV, Kleber M, Kooner JS, Perola M, Relton C, Ring SM, Rivadeneira F, Salomaa V, Spector TD, Stegle O, Toniolo D, Uitterlinden AG; arcOGEN Consortium; Understanding Society Scientific Group; UK10K Consortium; Barroso I, Gre… See abstract for full author list ➔ Tachmazidou I, et al. Am J Hum Genet. 2017 Jun 1;100(6):865-884. doi: 10.1016/j.ajhg.2017.04.014. Epub 2017 May 25. Am J Hum Genet. 2017. PMID: 28552196 Free PMC article.
  • Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.
    Iwaniec UT, Philbrick KA, Wong CP, Gordon JL, Kahler-Quesada AM, Olson DA, Branscum AJ, Sargent JL, DeMambro VE, Rosen CJ, Turner RT. Iwaniec UT, et al. Osteoporos Int. 2016 Oct;27(10):3091-101. doi: 10.1007/s00198-016-3634-3. Epub 2016 May 17. Osteoporos Int. 2016. PMID: 27189604 Free PMC article.
  • Sex-Dependent, Osteoblast Stage-Specific Effects of Progesterone Receptor on Bone Acquisition.
    Zhong ZA, Kot A, Lay YE, Zhang H, Jia J, Lane NE, Yao W. Zhong ZA, et al. J Bone Miner Res. 2017 Sep;32(9):1841-1852. doi: 10.1002/jbmr.3186. Epub 2017 Jul 13. J Bone Miner Res. 2017. PMID: 28569405 Free PMC article.
  • Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice.
    Keune JA, Wong CP, Branscum AJ, Iwaniec UT, Turner RT. Keune JA, et al. Sci Rep. 2017 Apr 12;7:46325. doi: 10.1038/srep46325. Sci Rep. 2017. PMID: 28402337 Free PMC article.
See all "Cited by" articles

References

    1. Prior JC 1990 Progesterone as a bone-trophic hormone. Endocr Rev 11:386–398 - PubMed
    1. Gallagher JC, Kable WT, Goldgar D 1991 Effect of progestin therapy on cortical and trabecular bone: comparison with estrogen. Am J Med 90:171–178 - PubMed
    1. Lindsay R, Hart DM, Purdie D, Ferguson MM, Clark AS, Kraszewski A 1978 Comparative effects of oestrogen and a progestogen on bone loss in postmenopausal women. Clin Sci Mol Med 54:193–195 - PubMed
    1. Lobo RA, McCormick W, Singer F, Roy S 1984 Depo-medroxyprogesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women. Obstet Gynecol 63:1–5 - PubMed
    1. Gallagher J 1981 Biochemical effects of estrogen and progesterone on calcium metabolism. In: DeLuca H, Parfitt A, Jee W, Johnston C, eds. Recent advances in osteoporosis. Baltimore: University Park Press; 215–224

Publication types

Substances