Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production.
Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production.
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DOI：
10.1016/j.cmet.2017.05.003
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发表时间：
2017-06-06
期刊：
影响因子：
29
通讯作者：
Mitchell JR
中科院分区：
文献类型：
--
作者：
Hine C;Kim HJ;Zhu Y;Harputlugil E;Longchamp A;Matos MS;Ramadoss P;Bauerle K;Brace L;Asara JM;Ozaki CK;Cheng SY;Singha S;Ahn KH;Kimmelman A;Fisher FM;Pissios P;Withers DJ;Selman C;Wang R;Yen K;Longo VD;Cohen P;Bartke A;Kopchick JJ;Miller R;Hollenberg AN;Mitchell JR
生长激素（GH）和甲状腺激素（TH）信号的减少与长寿和代谢健康有关。这些益处的机制尚不清楚，但可能与饮食限制（DR）的机制重叠，后者具有类似的益处。最近，我们发现硫化氢（H2S）在DR时增加，并且在介导DR益处跨越进化边界方面起着至关重要的作用。在这里，我们发现增加肝H2S生产在长寿的小鼠品系减少GH和/或TH的行动，并在细胞自主的方式后，血清撤出体外。GH和TH对肝脏H2S产生的负调节是加性的，并通过不同的机制发生，即TH对H2S产生酶胱硫醚γ-裂解酶（CGL）的直接转录抑制，以及GH对H2S产生的底物水平控制。缺乏CGL的小鼠未能下调全身T4代谢和循环IGF-1，揭示了H2S在调节关键长寿相关激素中的重要作用。生长激素（GH）抑制肝脏H2S的转录后产生甲状腺激素（TH）通过TRβ抑制胱硫醚γ-裂解酶和H2S水平H2S负调节循环TH和IGF-1水平甲状腺激素（TH）和生长激素（GH）活性降低是小鼠长寿遗传模型的标志。Hine等人发现TH和GH负调节长寿相关气体硫化氢的肝脏产生，其反馈负调节循环TH和IGF-1水平。
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. Hepatic H2S production capacity is elevated in long-lived hypopituitary mouse models Growth hormone (GH) represses hepatic H2S production post-transcriptionally Thyroid hormone (TH) acts via TRβ to repress cystathionine γ-lyase and H2S levels H2S negatively regulates circulating TH and IGF-1 levels Reduced thyroid hormone (TH) and growth hormone (GH) activity are hallmarks of genetic models of longevity in mice. Here, Hine et al. find that TH and GH negatively regulate hepatic production of the longevity-associated gas hydrogen sulfide, which feeds back to negatively regulate circulating TH and IGF-1 levels.
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影响因子：
7.8
作者：
Fontana L;Weiss EP;Villareal DT;Klein S;Holloszy JO
通讯作者：
Holloszy JO
影响因子：
7.4
作者：
Dacks, Penny A.;Moreno, Cesar L.;Kim, Esther S.;Marcellino, Bridget K.;Mobbs, Charles V.
通讯作者：
Mobbs, Charles V.
影响因子：
4.8
作者：
Coschigano, KT;Holland, AN;Kopchick, JJ
通讯作者：
Kopchick, JJ
DOI：
10.1124/jpet.105.092023
发表时间：
2006-02-01
影响因子：
3.5
作者：
Bian, JS;Yong, QC;Moore, PK
通讯作者：
Moore, PK
影响因子：
4
作者：
DIEGUEZ, C;JORDAN, V;SCANLON, MF
通讯作者：
SCANLON, MF