PUBLICATION
Gonadotropin releasing hormone - gonadotropes interactions revealed by pituitary single-cell transcriptomics in zebrafish
- Authors
- Tanaka, S., Yu, Y., Levavi-Sivan, B., Zmora, N., Zohar, Y.
- ID
- ZDB-PUB-241106-3
- Date
- 2024
- Source
- Endocrinology 165(12): (Journal)
- Registered Authors
- Levavi-Sivan, Berta, Yu, Yang, Zohar, Yonathan
- Keywords
- Gnrh, Lh, Pituitary, Reproduction, Transcriptomics, teleost
- Datasets
- GEO:GSE272806
- MeSH Terms
-
- Luteinizing Hormone, beta Subunit/genetics
- Luteinizing Hormone, beta Subunit/metabolism
- Transcriptome
- Female
- Gonadotropin-Releasing Hormone*/genetics
- Gonadotropin-Releasing Hormone*/metabolism
- Pyrrolidonecarboxylic Acid/analogs & derivatives
- Pyrrolidonecarboxylic Acid/metabolism
- Luteinizing Hormone/metabolism
- Gonadotrophs*/metabolism
- Single-Cell Analysis
- Animals
- Pituitary Gland*/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 39499852 Full text @ Endocrinology
Citation
Tanaka, S., Yu, Y., Levavi-Sivan, B., Zmora, N., Zohar, Y. (2024) Gonadotropin releasing hormone - gonadotropes interactions revealed by pituitary single-cell transcriptomics in zebrafish. Endocrinology. 165(12):.
Abstract
Gonadotropin-releasing hormone (GnRH) governs reproduction by regulating pituitary gonadotropins. Unlike most vertebrates, gnrh-/- zebrafish are fertile. To elucidate the role of the hypophysiotropic-Gnrh3 and other mechanisms regulating pituitary gonadotropes, we profiled the gene expression of all individual pituitary cells of wild-type and gnrh3-/- adult female zebrafish. The single-cell RNA-Seq showed that Lh and Fsh gonadotropes express the two gonadotropin beta subunits with a ratio of 140:1 (lhb:fshb) and 4:1 (fshb:lhb), respectively. Lh gonadotropes predominantly express genes encoding receptors for Gnrh (gnrhr2), thyroid hormone, estrogen, and steroidogenic factor 1 (SF1). No Gnrh receptor transcript was enriched in Fsh gonadotropes. Instead, cholecystokinin receptor-b and galanin receptor-1b transcripts were enriched in these cells. The loss of Gnrh3 gene in gnrh3-/- zebrafish resulted in downregulation of fshb in Lh gonadotropes and upregulation of pituitary hormones like thyroid-stimulating hormone, growth hormone, prolactin and proopiomelanocortin-a. Likewise, targeted chemogenetic ablation of Gnrh3 neurons led to a decrease in the number of fshb+, lhb+ and fshb+/lhb+ cells. Our studies suggest that Gnrh3 directly acts on Lh gonadotropes through Gnrhr2, but the outcome of this interaction is still unknown. Gnrh3 also regulates fshb expression in both gonadotropes, most likely via a non-Gnrh receptor route. Altogether, while Lh secretion and synthesis are likely regulated in a Gnrh-independent manner, Gnrh3 seems to play a role in the cellular organization of the pituitary. Moreover, the co-expression of lhb and fshb in both gonadotropes provides a possible explanation as to why gnrh3-/- zebrafish are fertile.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping