Parathyroid hormone (PTH) is one of the most important hormones responsible for bone turnover and calcium homeostasis, however, the mechanism underlying central neural regulation of PTH in mammals remains largely unknown. In this study, we identified the subfornical organ (SFO) and the paraventricular nucleus (PVN) as two important brain nuclei responded to serum PTH and calcium changes. Using chemogenetics, we found that serum PTH was suppressed by stimulation of SFOGABA neurons followed by a decrease in trabecular bone mass. Conversely, stimulation of SFOVGlut neurons promoted serum PTH and bone mass. The paraventricular nucleus (PVN) is downstream of the SFO, and chemogenetic activation of PVNCaMKII and PVNVGlut neurons induced an increase in serum PTH. These findings reveal important central neural nodes and will advance our understanding of the central neural regulation of PTH at the molecular, cellular and circuit level.
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