Brain atlas for glycoprotein hormone receptors at single-transcript level
Curation statements for this article:-
Curated by eLife
Evaluation Summary:
This paper will be very interesting to the large class of neuroscientists who study functional roles of glycoprotein hormone receptors in the central nervous system. It provides detailed tissue-selective gene and receptor distributions of the three anterior pituitary hormones, and thus likely facilitates further relevant studies by other scientists.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (eLife)
- Neuroscience (eLife)
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 subnuclei identified using the Atlas for the Mouse Brain in Stereotaxic Coordinates . We also identified Lhcgr transcripts in 401 brain regions, nuclei and subnuclei. 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.
Article activity feed
-
-
-
Evaluation Summary:
This paper will be very interesting to the large class of neuroscientists who study functional roles of glycoprotein hormone receptors in the central nervous system. It provides detailed tissue-selective gene and receptor distributions of the three anterior pituitary hormones, and thus likely facilitates further relevant studies by other scientists.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)
-
-
Reviewer #1 (Public Review):
Ryu V et al. performed a series of elegant studies to reveal a brain atlas for glycoprotein hormone receptors (i.e. TSHRs, LHCGRs, FSHRs) using combined coordinated methods and techniques including the RNAscope to detect mRNA at the single-transcript level. They find that these receptors and genes are differentially distributed in many brain regions, nuclei, and sub-nuclei. Generally, this is a timely and important study to reveal previously unknown but important central distributions of genes encoding anterior pituitary hormone receptors, providing a key resource for scientists to study the roles played by central anterior pituitary hormone receptor signaling in physiological and pathological conditions.
The experiments were designed and performed properly. The data were analyzed and interpreted accurately …
Reviewer #1 (Public Review):
Ryu V et al. performed a series of elegant studies to reveal a brain atlas for glycoprotein hormone receptors (i.e. TSHRs, LHCGRs, FSHRs) using combined coordinated methods and techniques including the RNAscope to detect mRNA at the single-transcript level. They find that these receptors and genes are differentially distributed in many brain regions, nuclei, and sub-nuclei. Generally, this is a timely and important study to reveal previously unknown but important central distributions of genes encoding anterior pituitary hormone receptors, providing a key resource for scientists to study the roles played by central anterior pituitary hormone receptor signaling in physiological and pathological conditions.
The experiments were designed and performed properly. The data were analyzed and interpreted accurately and presented logically in the manuscript. The conclusions of this paper were well supported by the data.
-
-
Reviewer #2 (Public Review):
This is a momentous work summing up brain hypophyseal localization. It is the culmination of a sustained programme of research by a number of these authors. This sequence of papers resulted in a paradigm shift in our understanding of such hormones. The present submission provides an invaluable reference source as well as a novel contribution to their field.
-
-
Reviewer #3 (Public Review):
Accumulating evidence supports the expression of anterior pituitary glycoprotein hormone family of receptors, namely FSHR, TSHR, and luteinizing hormone/human chorionic gonadotropin receptor (LHCGR), in various brain regions, and their function in regulating peripheral actions. However, the link between the stimulation of these receptors in the brain and the regulation of peripheral physiological processes remains poorly understood. Using RNAscope, a cutting-edge technology that detects single RNA transcripts, the authors created a comprehensive neuroanatomical atlas of glycoprotein hormone receptors in the mouse brain. Overall, these are a very comprehensive and well-done set of studies that offer new insights into the distributed brain network of anterior pituitary hormone receptors. The atlas provides an …
Reviewer #3 (Public Review):
Accumulating evidence supports the expression of anterior pituitary glycoprotein hormone family of receptors, namely FSHR, TSHR, and luteinizing hormone/human chorionic gonadotropin receptor (LHCGR), in various brain regions, and their function in regulating peripheral actions. However, the link between the stimulation of these receptors in the brain and the regulation of peripheral physiological processes remains poorly understood. Using RNAscope, a cutting-edge technology that detects single RNA transcripts, the authors created a comprehensive neuroanatomical atlas of glycoprotein hormone receptors in the mouse brain. Overall, these are a very comprehensive and well-done set of studies that offer new insights into the distributed brain network of anterior pituitary hormone receptors. The atlas provides an important resource for scientists to explore the link between the stimulation or inactivation of these receptors on somatic function.
-