Sex‐Related Effects of Nesfatin‐1 in the Pituitary

Neuroendocrine interaction between the hypothalamus, pituitary, and adrenal glands, known as the HPA axis, is responsible for regulation of the adaptive stress response. Nesfatin‐1, a potent anorexigenic peptide expressed in the hypothalamus, has been shown to play a role in the stress response by modulating HPA axis activity in rats. However, elucidation of nesfatin‐1's cognate receptor is necessary to assess the physiological relevance of these findings. Previous data on the nesfatin‐1 signaling pathway indicate involvement of a G‐protein‐coupled receptor. Furthermore, because the stress‐response is known to be sexually dimorphic, we hypothesized that the action and expression of nesfatin‐1 would be influenced by sex hormones. In cultured male rat pituitary cells, treatment with nesfatin‐1 elicits a robust cFos response, but no significant response was observed in female rat pituitary cells. In addition, expression of nesfatin‐1 in the female rat hypothalamus differed across stages of the estrus cycle. To determine the physiological relevance of nesfatin‐1's effects, we also began screening cell lines responsive to nesfatin‐1 for orphan GPCR expression to search for a candidate receptor. These studies suggest that both expression and function of nesfatin‐1 are regulated by sex hormones. Identification of the nesfatin‐1 receptor would potentially yield a novel therapeutic target for stress‐related disorders. Support or Funding Information NIH HL121456 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .