Expression profile of NGF-BDNF and Osteocalcin genes 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 and NGF are involved in energy and bone metabolism. NGF regulates fertility elevating LH in the female, Ost-/- mice show obesity and high LH in spite of decreased testosterone. To investigate the NGF-osteocalcin interaction we analyzed by RT-PCR the mRNA levels of NGF, BDNF, Ost. and their receptors p75NTR/NTRK1, TRKb and Gprc6a respectively in adipose WAT/BAT, reproductive organs, brain and bone(positive controls) of 3 months old female and male mice. Here, the mRNA levels of NGF and p75NTR are 50% higher in BAT than the brain. NGF and its receptors are down-regulated in WAT and bone in both genders. Osteocalcin and Gprc6a are up-regulated in bone and brain, downregulated 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 the ovaries/uterus, but down-regulated in the testes. The mRNA levels of p75NTR is respectively 300%, 100% and 50% higher in testis, ovaries and uterus than the brain. NTRK1 is down-regulated in all tissues. The Gprc6a is expressed in the testes, not in the ovaries and uterus. BDNF and TRKb are down-regulated in the sexual organs. Therefore, 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 the testes match the Gprc6a expression, and is responsible for higher LH in the Ost-/- mice. The animal care was performed in accordance with the DIRECTIVE 2010/63/EU. The protocol was approved by the Ethics Committee of the University of Bari, Italy