Endocrine Regulation of Male Fertility by the Skeleton
Open accessAbstract
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.
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In testis, osteocalcin binds to a specific receptor in Leydig cells, enhances testosterone synthesis, and increases fertility.
“In the testis, osteocalcin can bind to a specific receptor in Leydig cells and enhances testosterone synthesis and, consequently, increases fertility [206].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [206]
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References 60 · Cited by 628
- Authors
- Oury, F., Sumara, G., Sumara, O., Ferron, M., Chang, H., Smith, C. E., Hermo, L., Suarez, S., Roth, B. L., Ducy, P., & Karsenty, G.
- Affiliations
- Columbia University (US)
- Cornell University (US)
- McGill University (CA)
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 144
- Issue
- 5
- Pages
- 796-809
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3052787
- OpenAlex
- W2106343960
- Cited by
- 628
- References
- 60
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 32 · 2023: 38 · 2022: 23 · 2021: 45 · 2020: 50 · 2019: 45 · 2018: 39 · 2017: 45 · 2016: 52 · 2015: 43 · 2014: 45 · 2013: 49 · 2012: 50
- FWCI
- 64.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 905 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065439)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- osteocalcin, male fertility, osteoblasts, testosterone production, Leydig cells, G protein-coupled receptors, CREB, germ cell survival, bone as endocrine organ
- MeSH terms
- Animals, Bone and Bones, Cells, Cultured, Fertility, Humans, Leydig Cells, Male, Osteoblasts, Testis, Osteocalcin, Mice
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