title: Osteocalcin, a bone-derived hormone with important andrological implications.
abstract: Increasing evidence disclosed the existence of a novel multi-organ endocrine pathway, involving bone, pancreas and testis, of high penetrance in energy metabolism and male fertility. The main mediator of this axis is undercarboxylated osteocalcin (ucOC), a bone-derived protein-exerting systemic effects on tissues expressing the metabotropic receptor GPRC6A. The recognized effects of ucOC are the improvement of insulin secretion from the pancreas, the amelioration of systemic insulin sensitivity, in particular in skeletal muscle, and the stimulation of the global endocrine activity of the Leydig cell, including vitamin D 25-hydroxylation and testosterone production. The supporting evidence of this circuit in both animal and human models is here reviewed, with particular emphasis on the role of ucOC on testis function. The possible pharmacological modulation of this hormonal circuit for therapeutic aims is also discussed.
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Toni
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Nisio
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: M S
authors.initials: MS
authors.lastname: Rocca
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Rocco Ponce
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: A
authors.identifier: 0000-0002-0391-6570
authors.initials: A
authors.lastname: Ferlin
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: C
authors.identifier: 0000-0002-6576-2183
authors.initials: C
authors.lastname: Foresta
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism; D005298:Fertility; D005299:Fertility Agents / Q000627:therapeutic use; D006801:Humans; D006900:Hydroxylation; D008297:Male; D015675:Osteocalcin / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis; D014807:Vitamin D / Q000378:metabolism
chemical_list: D005299:Fertility Agents; C488584:GPRC6A protein, human; D043562:Receptors, G-Protein-Coupled; D015675:Osteocalcin; D014807:Vitamin D; D013739:Testosterone
keywords: hormone receptors; metabolic syndrome; subfertility; testosterone; vitamins