Brain atlas for glycoprotein hormone receptors at single-transcript level
- Icahn School of Medicine at Mount Sinai, United States
- Emory University, United States
- Alamak Biosciences, United States
- Memorial Sloan Kettering Cancer Center, United States
- Maine Medical Center Research Institute, United States
- 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.
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All data generated or analyzed during this study are included in the manuscript and supporting file.
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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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Brain atlas for glycoprotein hormone receptors at single-transcript level
eLife 11:e79612.
https://doi.org/10.7554/eLife.79612
