Hypothalamic-pituitary axis regulates hydrogen sulfide production
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2017-06-09
Date Acceptance
2017-05-11
Citation
Cell Metabolism, 2017, 25 (6), pp.1320-+
ISSN
1550-4131
Publisher
Elsevier
Start Page
1320
End Page
+
Journal / Book Title
Cell Metabolism
Volume
25
Issue
6
Copyright Statement
© 2017 The Authors. Published by Elsevier Inc. Thi is an open access article under a CC-BY license (https://creativecommons.org/licenses/by/4.0/)
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000402961500012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
098565/Z/12/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Endocrinology & Metabolism
CYSTATHIONINE-GAMMA-LYASE
THYROID-HORMONE RECEPTOR
LIFE-SPAN EXTENSION
LIVED MUTANT MICE
AMES DWARF MICE
GROWTH-FACTOR I
GENE-EXPRESSION
CALORIE RESTRICTION
STRESS RESISTANCE
DIETARY RESTRICTION
Publication Status
Published