Nerve growth factor/Brain-derived Neurotrophic Factor - Osteocalcin and oxytocin gene interaction in brain, bone, fat stores and reproductive organs of adult mice.

OBJECTIVE: That gonadal failure favors the appearance of osteoporosis while obesity seems to protect from osteoporosis support linking between bone, energy, and reproduction. The bone-derived osteocalcin (Ost), the neurotrophins BDNF/NGF and Oxytocin(Oxt) have effects on energy metabolism, bone mass, reproduction and brain functions suggesting a coordinated regulation. MATERIALS AND METHODS: 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. RESULTS: 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. 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 in bone in either genders while Oxtr in ovaries, in fat and bone. Up-regulation of NGF and related-receptors in fat is consistent with NGF as an energy regulator. Inverse correlation of NGF and BDNF in fat and bone, shows these exerting opposite effects on leptin with BDNF regulating bone. CONCLUSIONS: The up-regulation of p75NTR in testes matches Gprc6a expression and may be responsible for higher LH in Ost-/- mice. The pattern of expression of these molecules show a similar trend with Ost/NGF/Oxt/BDNF genes highly expressed in brain of male and female mice, while their receptors were expressed in reproductive organs showing a gender expression profile. This is consistent with the fact that these molecules have limited or no access through the blood brain barrier and adds evidences that the signalling of bone metabolism and fertility are released from CNS to act on peripheral tissues