FSH directly regulates bone mass

Cell. 2006 Apr 21;125(2):247-60. doi: 10.1016/j.cell.2006.01.051.

Abstract

Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Resorption*
  • Bone and Bones* / anatomy & histology
  • Bone and Bones* / physiology
  • Cell Differentiation
  • Cells, Cultured
  • Enzyme Activation
  • Estrogens / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Follicle Stimulating Hormone / genetics
  • Follicle Stimulating Hormone / metabolism*
  • GTP-Binding Protein alpha Subunit, Gi2 / metabolism
  • Humans
  • Hypogonadism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Osteoporosis / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, FSH / genetics
  • Receptors, FSH / metabolism
  • Signal Transduction / physiology

Substances

  • Estrogens
  • NF-kappa B
  • Protein Subunits
  • Receptors, FSH
  • Follicle Stimulating Hormone
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • GTP-Binding Protein alpha Subunit, Gi2