Peripartum dietary supplementation of a small-molecule inhibitor of tryptophan hydroxylase 1 compromises infant, but not maternal, bone

摘要

Long-term effects of breastfeeding on maternal bone are not fully understood. Excessive maternal bone loss stimulated by serotonin signaling during lactation may increase bone fragility later in life. We hypothesized that inhibiting nonneuronal serotonin activity by feeding a small-molecule inhibitor of the rate-limiting enzyme in serotonin synthesis tryptophan hydroxylase 1 (TPH1) would preserve maternal bone postweaning without affecting neonatal bone. Chow supplemented with the small-molecule TPHI inhibitor LP778902 (-100 mg/kg) or control chow was fed to C57BL/6 dams throughout pregnancy and lactation, and blood was collected on days I and 21 of lactation. Dams returned to a common diet postweaning and were aged to 3 or 9 mo postweaning. Pups were euthanized at weaning. The effect of TPHI inhibition on dam and pup femoral bone was determined by micro-computed tomography.