Editors' ChoiceReproductive Biology

Bones Promote Male Fertility

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Science Signaling  08 Mar 2011:
Vol. 4, Issue 163, pp. ec64
DOI: 10.1126/scisignal.4163ec64

Interaction between the reproductive system and bone physiology is well known in females, where loss of the sex steroid hormone estrogen during aging is a causative factor in bone loss or osteoporosis. Oury et al. now describe regulation in the other direction, in this case specific to males; osteocalcin, a peptide hormone produced in bone cells, controls production of the steroid hormone testosterone in the testes. Knockout mice lacking osteocalcin had smaller testes, decreased concentrations of testosterone in the blood, and reduced reproductive function. In Leydig cells of the testes, osteocalcin increased expression of genes that participate in testosterone biosynthesis and spermatogenesis, and it indirectly inhibited apoptosis of stem cells. Osteocalcin causes intracellular signaling events characteristic of those activated by heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors, and Oury et al. found that one such receptor, Gprc6a, was specifically expressed in Leydig cells. Binding of osteocalcin was not directly demonstrated, but mice with diminished expression of Gprc6a in Leydig cells showed impaired testicular function similar to that of animals lacking osteocalcin. Osteocalcin, which also regulates metabolism through effects on pancreatic β cells and fat cells, thus appears to have important physiological roles in coordinating energy metabolism, bone remodeling, and reproductive function. Smith and Saunders provide commentary.

F. Oury, G. Sumara, O. Sumara, M. Ferron, H. Chang, C. E. Smith, L. Hermo, S. Suarez, B. L. Roth, P. Ducy, G. Karsenty, Endocrine regulation of male fertility by the skeleton. Cell 144, 796–809 (2011). [PubMed]

L. B. Smith, P. T. K. Saunders, The skeleton: The new controller of male fertility? Cell 144, 642–643 (2011). [Online Journal]

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