Mechanisms of sex steroid effects on bone

Farhan Syed, Sundeep Khosla

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

Sex steroids play a major role in the regulation of bone turnover. Thus, gonadectomy in either sex is associated with an increase in bone remodeling, increased bone resorption, and a relative deficit in bone formation, resulting in accelerated bone loss. Recent physiological studies have established an important role for estrogen in regulating bone turnover not only in females, but also in males. Studies in mice with knock out of the estrogen receptor, aromatase, or androgen receptor have provided important insights into the in vivo mechanisms of sex steroid action on bone. The cellular and molecular mediators of sex steroid effects on the bone-forming osteoblasts and bone-resorbing osteoclasts are also being increasingly better defined. Estrogen inhibits bone remodeling by concurrently suppressing osteoblastogenesis and osteoclastogenesis from marrow precursors. Both estrogen and androgens inhibit bone resorption via effects on the receptor activator of NF-κB ligand (RANKL)/RANK/osteoprotegerin system, as well as by reducing the production of a number of pro-resorptive cytokines, along with direct effects on osteoclast activity and lifespan. Sex steroid effects on bone formation are also likely mediated by multiple mechanisms, including a prolongation of osteoblast lifespan via non-genotropic mechanisms, as well as effects on osteoblast differentiation and function. These pleiotropic actions of sex steroids on virtually all aspects of bone metabolism belie the importance of the skeleton not only in providing structural support for the body and in locomotion, but also as a dynamic tissue responsive, among other things, to the reproductive needs of the organism for calcium.

Original languageEnglish (US)
Pages (from-to)688-696
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number3
DOIs
StatePublished - Mar 18 2005

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Bone
Bone Remodeling
Steroids
Bone and Bones
Osteoblasts
Osteogenesis
Estrogens
Osteoclasts
Bone Resorption
RANK Ligand
Osteoprotegerin
Aromatase
Androgen Receptors
Locomotion
Skeleton
Knockout Mice
Estrogen Receptors
Androgens
Bone Marrow
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Mechanisms of sex steroid effects on bone. / Syed, Farhan; Khosla, Sundeep.

In: Biochemical and Biophysical Research Communications, Vol. 328, No. 3, 18.03.2005, p. 688-696.

Research output: Contribution to journalArticle

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