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Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production

2017; Cell Press; Volume: 25; Issue: 6 Linguagem: Inglês

10.1016/j.cmet.2017.05.003

1932-7420

Christopher Hine, Hyo-Jeong Kim, Yan Zhu, Eylul Harputlugil, Alban Longchamp, Marina Souza Matos, Preeti Ramadoss, Kevin T. Bauerle, Lear E. Brace, John M. Asara, C. Keith Ozaki, Sheue-yann Cheng, Subhankar Singha, Kyo Han Ahn, Alec C. Kimmelman, Ffolliott M. Fisher, Pavlos Pissios, Dominic J. Withers, Colin Selman, Rui Wang, Kelvin Yen, Valter D. Longo, Pinchas Cohen, Andrzej Bartke, John J. Kopchick, Richard A. Miller, Anthony N. Hollenberg, James R. Mitchell,

Genetic and Kidney Cyst Diseases

Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (H2S) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries. Here we found increased hepatic H2S production in long-lived mouse strains of reduced GH and/or TH action, and in a cell-autonomous manner upon serum withdrawal in vitro. Negative regulation of hepatic H2S production by GH and TH was additive and occurred via distinct mechanisms, namely direct transcriptional repression of the H2S-producing enzyme cystathionine γ-lyase (CGL) by TH, and substrate-level control of H2S production by GH. Mice lacking CGL failed to downregulate systemic T4 metabolism and circulating IGF-1, revealing an essential role for H2S in the regulation of key longevity-associated hormones.