title: Endocrine regulation of male fertility by the skeleton.
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.
authors.affiliation: Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
authors.forename: Franck
authors.initials: F
authors.lastname: Oury
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Sumara
authors.forename: Olga
authors.initials: O
authors.lastname: Sumara
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ferron
authors.forename: Haixin
authors.initials: H
authors.lastname: Chang
authors.forename: Charles E
authors.initials: CE
authors.lastname: Smith
authors.forename: Louis
authors.initials: L
authors.lastname: Hermo
authors.forename: Susan
authors.initials: S
authors.lastname: Suarez
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Patricia
authors.initials: P
authors.lastname: Ducy
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D002478:Cells, Cultured; D005298:Fertility; D006801:Humans; D007985:Leydig Cells / Q000502:physiology; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000502:physiology; D015675:Osteocalcin / Q000502:physiology*; D013737:Testis / Q000502:physiology
chemical_list: D015675:Osteocalcin