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PMID: 21333348 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Endocrine regulation of male fertility by the skeleton.

Cell ·Vol. 144 ·No. 5 ·2011-03-04 ·Pages 796-809

Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G

Abstract

Interactions between bone and the reproductive system have until now been thought to be limited to the regulation of bone remodeling by the gonads. We now show that, in males, bone acts as a regulator of fertility. Using coculture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, though they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function. By binding to a G protein-coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymes that is required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin and provides the first evidence that the skeleton is an endocrine regulator of reproduction.

MeSH Terms
Animals Bone and Bones/physiology Cells, Cultured Fertility Humans Leydig Cells/physiology Male Mice Osteoblasts/physiology Osteocalcin/physiology Testis/physiology
Chemicals
Osteocalcin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Oury Franck
Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
Sumara Grzegorz
Sumara Olga
Ferron Mathieu
Chang Haixin
Smith Charles E
Hermo Louis
Suarez Susan
Roth Bryan L
Ducy Patricia
Karsenty Gerard
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2011.02.004
Published
2011-03-04
Epub
2011-00-17
Pages
796-809
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3052787
Subset
IM
Grants
NICHD NIH HHS · R01 HD065439 · United States
NICHD NIH HHS · R01 HD065439-17 · United States
NICHD NIH HHS · R01 HD065439-18 · United States
Corrections
CommentIn
PMID: 21376228
External Links
PubMed source DOI: 10.1016/j.cell.2011.02.004 PMC Full Text View journal details
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