Transgenic mice offers powerful tools to study integrative physiology especially to study a specific gene function in a whole organism. Using transgenic mice revealed the role of the skeleton on fertility and energy metabolism.Central control of bone mass. Leptin acts on brain stem and decrease serotonin neuron (SN) activity. SN project on hypothalamus to control bone mass (VMH nucleus) and appetite (arcuate nucleus). Brain serotonin reduces sympathetic tone and increases bone mass.Bone regulates energy metabolism. Osteocalcin is a new hormone secreted by osteoblast which stimulates insulin secretion and reduces insulin resistance. We show here for the first time that the action of osteocalcin on blood glucose is conserved in humans. Osteoid osteoma can be considered as a benign tumor secreting osteocalcin. In a large cohort of elderly males, osteocalcin is negatively associated to blood glucose, metabolic syndrome and abdominal aortic calcifications. Sex steroids and bone. First we show aromatase inhibitor induces bone loss after one year of adjuvant therapy in breast cancer. Second we identified a patient presenting severe oligospermia, metabolic syndrome and a F464Y mutation of the GPRC6A osteocalcin receptor. We identified a new independent pancreas- bone – testis axis to regulate fertility.
Integrative physiology of bone, energy metabolism and fertility : role of osteocalcin and sex steroids