Bone growth and turnover in progesterone receptor knockout mice.

Journal Article · Thu May 01 04:00:00 EDT 2008 · Endocrinology, 149(5):2383-2390

DOI:https://doi.org/10.1210/en.2007-1247· OSTI ID:948404

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

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 948404
• Report Number(s): PNNL-SA-57031
• Journal Information: Endocrinology, 149(5):2383-2390, Journal Name: Endocrinology, 149(5):2383-2390 Journal Issue: 5 Vol. 149; ISSN 0013-7227; ISSN ENDOAO
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AGING
FEMALES
GENES
METABOLISM
MICE
MUTATIONS
PROGESTERONE
TIBIA