Osteocalcin interacts with Brain-derived Neurotrophic Factor, Nerve Growth Factor but not Oxytocin in the regulation of bone, energy, brain and reproductive functions.

Osteocalcin, the neurotrophins BDNF/NGF and Oxytocin(Oxt) have pleiotropic effects on energy metabolism, bone mass, reproduction and brain functions suggesting a coordinated regulation. The carboxylated osteocalcin(Ost) acts on bone, while the uncarboxylated Ost shows hormone-like actions. NGF regulates female fertility elevating LH, Ost-/- mice show high LH in spite of decreased testosterone. BDNF/NGF-Oxt-Ost interactions was investigated by RT-PCR measuring mRNA levels of NGF, BDNF, Oxt, Ost and their receptors p75NTR/NTRK1, TRKb, Oxtr and Gprc6a in brain, bone, WAT/BAT and reproductive organs, of 3 months old female and male mice using brain and bone as positive controls, respectively. NGF and p75NTR expression is 50% higher in BAT than brain and are down-regulated in WAT and bone in both genders. Ost and Gprc6a are upregulated in bone and brain, down-regulated in BAT/WAT. BDNF and TRKb expression in bone is higher than brain, but lower in BAT/WAT; TRKb is down-regulated in bone and up-regulated in adipose tissue. NGF is up-regulated in ovaries/uterus, but down-regulated in testes. p75NTR is respectively 300%, 100% and 50% higher in testis, ovaries and uterus than brain. NTRK1 is down-regulated in all tissues. The Gprc6a is expressed in testes, not in ovaries and uterus. BDNF and TRKb are down-regulated in reproductive organs. Oxt is expressed in brain and with minor extend in bone in either genders while Oxtr in ovaries, a significant expression level is observed in fat and bone. The up-regulation of NGF and related-receptors in fat is consistent with NGF as energy regulator. The up-regulation of p75NTR matches the Gprc6a in testes, while inverse correlation of NGF and BDNF in fat and bone, shows these exerting opposite effects on leptin with BDNF regulating bone. BDNF-NGF-Ost genes interaction is observed. BDNF may regulate the exclusive actions of carboxylated Ost on bone, while NGF modulates the uncarboxylated Ost hormonal actions