Brain atlas for glycoprotein hormone receptors at single-transcript level

  1. Vitaly Ryu
  2. Anisa Azatovna Gumerova
  3. Funda Korkmaz
  4. Seong Su Kang
  5. Pavel Katsel
  6. Sari Miyashita
  7. Hasni Kannangara
  8. Liam Cullen
  9. Pokman Chan
  10. Tan-Chun Kuo
  11. Ashley Padilla
  12. Farhath Sultana
  13. Soleil A Wizman
  14. Natan Kramskiy
  15. Samir Zaidi
  16. Se-Min Kim
  17. Maria I New
  18. Clifford J Rosen
  19. Ki A Goosens
  20. Tal Frolinger
  21. Vahram Haroutunian
  22. Keqiang Ye
  23. Daria Lizneva
  24. Terry F Davies
  25. Tony Yuen  Is a corresponding author
  26. Mone Zaidi  Is a corresponding author
  1. Icahn School of Medicine at Mount Sinai, United States
  2. Emory University, United States
  3. Alamak Biosciences, United States
  4. Memorial Sloan Kettering Cancer Center, United States
  5. Maine Medical Center Research Institute, United States
  6. Chinese Academy of Sciences, China

Abstract

There is increasing evidence that anterior pituitary hormones, traditionally thought to have unitary functions in regulating single endocrine targets, act on multiple somatic tissues, such as bone, fat, and liver. There is also emerging evidence for anterior pituitary hormone action on brain receptors in mediating central neural and peripheral somatic functions. Here, we have created the most comprehensive neuroanatomical atlas on the expression of TSHR, LHCGR and FSHR. We have used RNAscope, a technology that allows the detection of mRNA at single-transcript level, together with protein level validation, to document Tshr expression in 173 and Fshr expression in 353 brain regions, nuclei and sub-nuclei identified using the Atlas for the Mouse Brain in Stereotaxic Coordinates. We also identified Lhcgr transcripts in 401 brain regions, nuclei and sub-nuclei. Complementarily, we used ViewRNA, another single-transcript detection technology, to establish the expression of FSHR in human brain samples, where transcripts were co-localized in MALAT1 positive neurons. In addition, we show high expression for all three receptors in the ventricular region-with yet unknown functions. Intriguingly, Tshr and Fshr expression in the ependymal layer of the third ventricle was similar to that of the thyroid follicular cells and testicular Sertoli cells, respectively. In contrast, Fshr was localized to NeuN-positive neurons in the granular layer of the dentate gyrus in murine and human brain-both are Alzheimer's disease vulnerable regions. Our atlas thus provides a vital resource for scientists to explore the link between the stimulation or inactivation of brain glycoprotein hormone receptors on somatic function. New actionable pathways for human disease may be unmasked through further studies.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file.

Article and author information

Author details

  1. Vitaly Ryu

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8068-4577
  2. Anisa Azatovna Gumerova

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  3. Funda Korkmaz

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  4. Seong Su Kang

    Department of Pathology, Emory University, Atlanta, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2517-9962
  5. Pavel Katsel

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8076-0162
  6. Sari Miyashita

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  7. Hasni Kannangara

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  8. Liam Cullen

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  9. Pokman Chan

    Alamak Biosciences, Beverly, United States
    Competing interests
    No competing interests declared.
  10. Tan-Chun Kuo

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5301-755X
  11. Ashley Padilla

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  12. Farhath Sultana

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  13. Soleil A Wizman

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  14. Natan Kramskiy

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  15. Samir Zaidi

    Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    No competing interests declared.
  16. Se-Min Kim

    Department of Medicine and of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  17. Maria I New

    Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  18. Clifford J Rosen

    Maine Medical Center Research Institute, Scarborough, United States
    Competing interests
    No competing interests declared.
  19. Ki A Goosens

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5246-2261
  20. Tal Frolinger

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  21. Vahram Haroutunian

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    Vahram Haroutunian, has received consultation fees from Synaptec to Cold Spring Harbor Laboratories.
  22. Keqiang Ye

    Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
    Competing interests
    Keqiang Ye, Reviewing editor, eLife.Is an inventor of a pending patent application on the use of FSH as a target for preventing Alzheimer's disease. The latter patent is jointly owned by ISSMS and Emory University, and would be recipient of royalties, per institutional policy..
  23. Daria Lizneva

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  24. Terry F Davies

    Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    Terry F Davies, has received payments from Kronus Inc, Starr, ID as a Board member and for various books and ebooks..
  25. Tony Yuen

    Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, United States
    For correspondence
    Tony.yuen@mountsinai.org
    Competing interests
    Tony Yuen, Reviewing editor, eLife.
  26. Mone Zaidi

    Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, United States
    For correspondence
    mone.zaidi@mountsinai.org
    Competing interests
    Mone Zaidi, Senior editor, eLife.Is an inventor on issued patents on inhibiting FSH for the prevention and treatment of osteoporosis and obesity: United States: 8,435,948 (2013) and 11,034,761 (2021). Is also an inventor on pending patent application on composition and use of humanized monoclonal anti-FSH antibodies. These patents are owned by Icahn School of Medicine at Mount Sinai (ISSMS), and would be recipient of royalties, per institutional policy. Is an inventors of a pending patent application on the use of FSH as a target for preventing Alzheimer's disease. The latter patent is jointly owned by ISSMS and Emory University, and would be recipient of royalties, per institutional policy. Also consults for Gershon Lehmann, Guidepoint and Coleman groups, and is Deputy Editor for eLife and Editor for Marrow (Annals of The New York Academy of Sciences)-both positions are compensated..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5911-9522

Funding

National Institute on Aging (U19 AG060917)

  • Clifford J Rosen
  • Mone Zaidi

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK113627)

  • Terry F Davies
  • Mone Zaidi

National Institute on Aging (R01 AG074092)

  • Tony Yuen
  • Mone Zaidi

National Institute on Aging (U01 AG073148)

  • Tony Yuen
  • Mone Zaidi

National Institute on Aging (R01 AG071870)

  • Se-Min Kim
  • Tony Yuen
  • Mone Zaidi

National Institute of General Medical Sciences (P20 GM121301)

  • Clifford J Rosen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were approved by the Mount Sinai Institutional Animal Care and Use Committee (approval number IACUC-2018-0047) and are in accordance with Public Health Service and United States Department of Agriculture guidelines.

Copyright

© 2022, Ryu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Vitaly Ryu
  2. Anisa Azatovna Gumerova
  3. Funda Korkmaz
  4. Seong Su Kang
  5. Pavel Katsel
  6. Sari Miyashita
  7. Hasni Kannangara
  8. Liam Cullen
  9. Pokman Chan
  10. Tan-Chun Kuo
  11. Ashley Padilla
  12. Farhath Sultana
  13. Soleil A Wizman
  14. Natan Kramskiy
  15. Samir Zaidi
  16. Se-Min Kim
  17. Maria I New
  18. Clifford J Rosen
  19. Ki A Goosens
  20. Tal Frolinger
  21. Vahram Haroutunian
  22. Keqiang Ye
  23. Daria Lizneva
  24. Terry F Davies
  25. Tony Yuen
  26. Mone Zaidi
(2022)
Brain atlas for glycoprotein hormone receptors at single-transcript level
eLife 11:e79612.
https://doi.org/10.7554/eLife.79612

Share this article

https://doi.org/10.7554/eLife.79612

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