Format

Send to

Choose Destination
Cell Metab. 2017 Jun 6;25(6):1320-1333.e5. doi: 10.1016/j.cmet.2017.05.003.

Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production.

Author information

1
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
2
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
3
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Surgery, Heart and Vascular Center Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
5
Department of Surgery, Heart and Vascular Center Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
6
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
7
Department of Chemistry, Center for Electro-Photo Behaviors in Advanced Molecular Systems, POSTECH, 77 Cheongam-Ro, Nam-Gu, Pohang 790-784, Republic of Korea.
8
Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
9
Medical Research Council Clinical Science Centre, Imperial College, London W12 0NN, UK.
10
Glasgow Ageing Research Network, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
11
Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada.
12
Department of Biological Sciences, Longevity Institute, School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
13
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
14
Edison Biotechnology Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
15
Department of Pathology & Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA.
16
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: thollenb@bidmc.harvard.edu.
17
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: jmitchel@hsph.harvard.edu.

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.

KEYWORDS:

FGF21; IGF-1; IRS-1; autophagy; cystathionine γ-lyase; growth hormone; hydrogen sulfide; hypopituitary dwarfism; longevity; thyroid hormone

PMID:
28591635
PMCID:
PMC5722247
DOI:
10.1016/j.cmet.2017.05.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center