Nerve Growth Factor/Brain-derived Neurotrophic Factor, Osteocalcin and Oxytocin genes relationship in brain, bone, fat stores and reproductive organs.

Bone mass, metabolism and reproduction are regulated coordinately. The bone-derived osteocalcin (Ost) favors insulin sensitivity, male fertility and neurogenesis. The neurotrophins BDNF/NGF and oxytocin (Oxt) are involved in energy and bone metabolism. NGF regulates fertility elevating LH in female, Ost-/- mice show obesity and high LH in spite of decreased testosterone. To investigate the NGF/BDNF-Oxt-Ost interactions we analyzed by RT-PCR the 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. Brain and bone were used as positive controls respectively. NGF and p75NTR expression is 50% higher in BAT than brain. NGF and its receptors are downregulated 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 downregulated in bone and up-regulated in adipose tissue. NGF is up-regulated in ovaries/uterus, but down-regulated in the testes. p75NTR is respectively 300%, 100% and 50% higher in testis, ovaries and uterus than brain. NTRK1 is downregulated in all tissues. The Gprc6a is expressed in testes, not in ovaries and uterus. BDNF and TRKb are downregulated in sexual organs. Oxt is markedly expressed in brain and with minor extend in bone in either genders, while Oxtr in ovaries although 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 an energy regulator. The inverse correlation of NGF and BDNF in fat and bone, shows these exerting opposite effects on leptin with BDNF regulating bone. The up-regulation of p75NTR in testes matches the Gprc6a expression in the same organ. Gene correlation analysis shows the existence of an interaction between NGF and osteocalcin. Therefore, we speculate that NGF can be a physiologic mediator of osteocalcin both peripherally regulating steroid production in Leydig cell in the testosterone deficient OST-/-, and centrally thought the sprouting of new synapses in this cognitively impaired mice. The pattern of expression of these molecules and their receptors show a similar trend with Ost, NGF, Oxt and BDNF genes highly expressed in brain of both genders, while their receptors were expressed in the reproductive organs showing a gender expression profile. These data add evidences that the signalling of bone metabolism and reproduction are released from CNS to act on peripheral tissues.