LEP and osteonecrosis: As fat accumulation at the necrotic regions of the femoral head is also related to GC-induced osteonecrosis, we eliminated the classical ascending pathway to determine if leptin, mainly secreted by adipocytes, might inhibit bone formation by hyperactivation of sympathetic tone in the hypothalamus.40 We found that GCs inhibited sympathetic tone predominantly due to the imbalance of nuclear GR and MR activation in the PVN of the hypothalamus.