Hypothalamic-pituitary axis regulates hydrogen sulfide production

Hine, C. et al. (2017) Hypothalamic-pituitary axis regulates hydrogen sulfide production. Cell Metabolism, 25(6), 1320-1333.e5. (doi: 10.1016/j.cmet.2017.05.003) (PMID:28591635) (PMCID:PMC5722247)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Selman, Professor Colin
Authors: Hine, C., Kim, H.-J., Zhu, Y., Harputlugil, E., Longchamp, A., Matos, M. S., Ramadoss, P., Bauerle, K., Brace, L., Asara, J. M., Ozaki, C. K., Cheng, S.-y., Singha, S., Ahn, K. H., Kimmelman, A., Fisher, F. M., Pissios, P., Withers, D. J., Selman, C., Wang, R., Yen, K., Longo, V. D., Cohen, P., Bartke, A., Kopchick, J. J., Miller, R., Hollenberg, A. N., and Mitchell, J. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Cell Metabolism
Publisher:Elsevier (Cell Press)
ISSN:1550-4131
ISSN (Online):1932-7420
Published Online:09 June 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cell Metabolism 25(6): 1320-1333.e5
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
638451Dissecting the mechanisms underlying lifespan extension in insulin signalling mutant miceColin SelmanBiotechnology and Biological Sciences Research Council (BBSRC)BB/H012850/2RI BIODIVERSITY ANIMAL HEALTH & COMPMED