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Title: Bone growth and turnover in progesterone receptor knockout mice.

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 mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks 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 was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging 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 attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
948404
Report Number(s):
PNNL-SA-57031
Journal ID: ISSN 0013-7227; ENDOAO; TRN: US200906%%328
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Endocrinology, 149(5):2383-2390; Journal Volume: 149; Journal Issue: 5
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AGING; FEMALES; GENES; METABOLISM; MICE; MUTATIONS; PROGESTERONE; TIBIA

Citation Formats

Rickard, David J., Iwaniec, Urszula T., Evans, Glenda, Hefferan, Theresa E., Hunter, Jaime C., Waters, Katrina M., Lydon, John P., O'Malley, Bert W., Khosla, Sundeep, Spelsberg, Thomas C., and Turner, Russell T. Bone growth and turnover in progesterone receptor knockout mice.. United States: N. p., 2008. Web. doi:10.1210/en.2007-1247.
Rickard, David J., Iwaniec, Urszula T., Evans, Glenda, Hefferan, Theresa E., Hunter, Jaime C., Waters, Katrina M., Lydon, John P., O'Malley, Bert W., Khosla, Sundeep, Spelsberg, Thomas C., & Turner, Russell T. Bone growth and turnover in progesterone receptor knockout mice.. United States. doi:10.1210/en.2007-1247.
Rickard, David J., Iwaniec, Urszula T., Evans, Glenda, Hefferan, Theresa E., Hunter, Jaime C., Waters, Katrina M., Lydon, John P., O'Malley, Bert W., Khosla, Sundeep, Spelsberg, Thomas C., and Turner, Russell T. Thu . "Bone growth and turnover in progesterone receptor knockout mice.". United States. doi:10.1210/en.2007-1247.
@article{osti_948404,
title = {Bone growth and turnover in progesterone receptor knockout mice.},
author = {Rickard, David J. and Iwaniec, Urszula T. and Evans, Glenda and Hefferan, Theresa E. and Hunter, Jaime C. and Waters, Katrina M. and Lydon, John P. and O'Malley, Bert W. and Khosla, Sundeep and Spelsberg, Thomas C. and Turner, Russell T.},
abstractNote = {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 mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks 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 was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging 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 attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.},
doi = {10.1210/en.2007-1247},
journal = {Endocrinology, 149(5):2383-2390},
number = 5,
volume = 149,
place = {United States},
year = {Thu May 01 00:00:00 EDT 2008},
month = {Thu May 01 00:00:00 EDT 2008}
}