Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice

Allison, S. J., Baldock, P., Sainsbury, A., Enriquez, R., Lee, N. J., Lin, E. J. D., Klugman, M., During, M., Eisman, J. A., Li, M., Pan, L. C., Herzog, H. and Gardiner, E. M. (2006) Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice. Journal of Biological Chemistry, 281 33: 23436-23444. doi:10.1074/jbc.M604839200

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Author Allison, S. J.
Baldock, P.
Sainsbury, A.
Enriquez, R.
Lee, N. J.
Lin, E. J. D.
Klugman, M.
During, M.
Eisman, J. A.
Li, M.
Pan, L. C.
Herzog, H.
Gardiner, E. M.
Title Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1074/jbc.M604839200
Open Access Status File (Publisher version)
Volume 281
Issue 33
Start page 23436
End page 23444
Total pages 9
Editor H. Tabor
Place of publication USA
Publisher American Society for Biochemistry and Molecular Biology Inc
Collection year 2006
Language eng
Subject C1
320307 Medical Biochemistry - Other
730105 Endocrine organs and diseases (incl. diabetes)
Abstract Reduction in levels of sex hormones at menopause in women is associated with two common, major outcomes, the accumulation of white adipose tissue, and the progressive loss of bone because of excess osteoclastic bone resorption exceeding osteoblastic bone formation. Current antiresorptive therapies can reduce osteoclastic activity but have only limited capacity to stimulate osteoblastic bone formation and restore lost skeletal mass. Likewise, the availability of effective pharmacological weight loss treatments is currently limited. Here we demonstrate that conditional deletion of hypothalamic neuropeptide Y2 receptors can prevent ongoing bone loss in sex hormone-deficient adult male and female mice. This benefit is attributable solely to activation of an anabolic osteoblastic bone formation response that counterbalances persistent elevation of bone resorption, suggesting the Y2-mediated anabolic pathway to be independent of sex hormones. Furthermore, the increase in fat mass that typically occurs after ovariectomy is prevented by germ line deletion of Y2 receptors, whereas in male mice body weight and fat mass were consistently lower than wild-type regardless of sex hormone status. Therefore, this study indicates a role for Y2 receptors in the accumulation of adipose tissue in the hypogonadal state and demonstrates that hypothalamic Y2 receptors constitutively restrain osteoblastic activity even in the absence of sex hormones. The increase in bone formation after release of this tonic inhibition suggests a promising new avenue for osteoporosis treatment.
Keyword Biochemistry & Molecular Biology
Postmenopausal Women
Parathyroid-hormone
Y2 Receptors
Ob/ob Mice
Osteoporosis
Body
Expression
Osteoblasts
Ovariectomy
Alendronate
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 20:01:02 EST