Bone mass, metabolism and reproduction require a coordinated regulation. 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-osteocalcin- BDNF-Oxt interaction we analyzed by RT-PCR the mRNA levels of NGF, BDNF, Oxt, Ost and their receptors p75NTR/NTRK1, TRKb, Oxtr and Gprc6a in brain and bone, adipose WAT/BAT and reproductive organs, of 3 months old female and male mice. Brain and bone were used as positive controls respectively. The mRNA levels of NGF and p75NTR are 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. The mRNA levels of 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 the sexual organs. The Oxt gene is markedly expressed in brain and with minor extend in bone in either genders, while the Oxtr in ovaries although a significant level of expression is observed in adipose tissues and bone. The up-regulation of NGF and related-receptors in fat are 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 match the Gprc6a expression, and may be responsible for the higher LH in the Ost-/- 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 male and female mice, while their receptors were instead expressed in the 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 add evidences that the signalling of bone metabolism and fertility are released from CNS to act on peripheral tissues.
NGF-BDNF-Osteocalcin and oxytocin gene interaction in brain, bone, fat stores and reproductive organs
CAMERINO, CLAUDIA;CONTE, ELENA;TRICARICO, Domenico
2015-01-01
Abstract
Bone mass, metabolism and reproduction require a coordinated regulation. 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-osteocalcin- BDNF-Oxt interaction we analyzed by RT-PCR the mRNA levels of NGF, BDNF, Oxt, Ost and their receptors p75NTR/NTRK1, TRKb, Oxtr and Gprc6a in brain and bone, adipose WAT/BAT and reproductive organs, of 3 months old female and male mice. Brain and bone were used as positive controls respectively. The mRNA levels of NGF and p75NTR are 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. The mRNA levels of 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 the sexual organs. The Oxt gene is markedly expressed in brain and with minor extend in bone in either genders, while the Oxtr in ovaries although a significant level of expression is observed in adipose tissues and bone. The up-regulation of NGF and related-receptors in fat are 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 match the Gprc6a expression, and may be responsible for the higher LH in the Ost-/- 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 male and female mice, while their receptors were instead expressed in the 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 add evidences that the signalling of bone metabolism and fertility are released from CNS to act on peripheral tissues.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
