The Essential Role of SIRT1 in Hypothalamic-Pituitary Axis

Abstract

The endocrine system plays an essential role in the physiological adaptation to malnutrition. The adaptive response of various hormones directs the energy utilization toward the survival functions and away from growth and reproduction. Particularly, the hypothalamic pituitary axis plays an integral and a central role in the regulation of endocrine organs. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that is activated in response to calorie restriction (CR). SIRT1 is involved in cellular processes via the deacetylation of histone as well as various transcription factors and signal transduction molecules and thereby modulates the endocrine/metabolic functions. There is much evidence to demonstrate clearly that SIRT1 in the hypothalamus, pituitary gland, and other target organs modifies the synthesis, secretion, and activities of hormones and in turn induces the adaptive responses. In this review, we discussed the role of SIRT1 in the hypothalamic pituitary axis and its pathophysiological significance.

Keywords: SIRT1; adaptation; calorie restriction; hypothalamus; pituitary.

Figure 1

The mechanisms through which SIRT1 regulates STAT5 activation by GH. (A) In the fed condition, the SH2 domain of STAT5 recognizes and binds to Tyr-phosphorylated GHR, causing JAK2 to phosphorylate and activate STAT5. (B) In the fasting condition, SIRT1 is activated and interacts with STAT5, thereby deacetylating Lys residues adjacent to the SH2 domain of STAT5. This results in an impaired ability to bind Tyr-phosphorylated GHR, which inhibits activation of STAT5. Excerpt from, Yamamoto et al. (60).