GnRH—Gonadotropes Interactions Revealed by Pituitary Single-cell Transcriptomics in Zebrafish

dc.contributor.authorTanaka, Sakura
dc.contributor.authorYu, Yang
dc.contributor.authorLevavi-Sivan, Berta
dc.contributor.authorZmora, Nilli
dc.contributor.authorZohar, Yonathan
dc.date.accessioned2024-12-11T17:02:24Z
dc.date.available2024-12-11T17:02:24Z
dc.date.issued2024-11-06
dc.description.abstractGonadotropin-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.
dc.description.sponsorshipUS National Science Foundation Division of Integrative Organismal Systems NSF-BSF #1947541: Studying the Compensatory Mechanisms Underlying Gene Loss-of-Function in the Nervous System.
dc.description.urihttps://academic.oup.com/endo/advance-article/doi/10.1210/endocr/bqae151/7876481
dc.format.extent11 pages
dc.genrejournal articles
dc.identifierdoi:10.13016/m2dszc-lluv
dc.identifier.citationTanaka, Sakura, Yang Yu, Berta Levavi-Sivan, Nilli Zmora, and Yonathan Zohar. “GnRH—Gonadotropes Interactions Revealed by Pituitary Single-Cell Transcriptomics in Zebrafish.” Endocrinology, November 6, 2024, bqae151. https://doi.org/10.1210/endocr/bqae151.
dc.identifier.urihttps://doi.org/10.1210/endocr/bqae151
dc.identifier.urihttp://hdl.handle.net/11603/37063
dc.language.isoen_US
dc.publisherOxford University Press
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Department of Marine Biotechnology
dc.relation.ispartofUMBC Student Collection
dc.relation.ispartofUMBC Philosophy Department
dc.relation.ispartofUMBC Faculty Collection
dc.rightsAttribution 4.0 International CC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleGnRH—Gonadotropes Interactions Revealed by Pituitary Single-cell Transcriptomics in Zebrafish
dc.title.alternativeGonadotropin releasing hormone-gonadotropes interactions revealed by pituitary single-cell transcriptomics in zebrafish
dc.typeText
dcterms.creatorhttps://orcid.org/0000-0003-3051-6975
dcterms.creatorhttps://orcid.org/0009-0008-9814-2790
dcterms.creatorhttps://orcid.org/0000-0003-1324-2458
dcterms.creatorhttps://orcid.org/0000-0003-1092-3557

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