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Livio Casarini, Nafis Rahman, Eric Reiter, Pascale Crépieux, Adolfo Rivero-Müller, Kim C Jonas, T Rajendra Kumar, Alfredo Ulloa-Aguirre, Stephen Franks, Daniel J Bernard, Stine Gry Kristensen, John S Davis, George R Bousfield, James A Dias, Claus Y Andersen, David J Handelsman, Ilpo T Huhtaniemi, Manuela Simoni, Comment on “Atlas of Fshr Expression From Novel Reporter Mice”, Endocrinology, Volume 166, Issue 5, May 2025, bqaf066, https://doi.org/10.1210/endocr/bqaf066
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In recent years, there have been controversial claims of extragonadal effects of follicle-stimulating hormone (FSH). A paper by Chen et al (1) recently published in eLife further muddies the waters, though its intent was to provide clarity. Chen et al developed a new transgenic reporter mouse designed to map FSH receptor (FSHR) expression throughout the body. Using CRISPR/Cas9, the authors reportedly inserted a DNA fragment encoding a P2A-ZsGreen fluorescent protein between the end of the Fshr coding sequence and its 3′ untranslated region. These mice were expected to express a bicistronic Fshr/ZsGreen transcript under the control of the endogenous Fshr regulatory sequences. If successful, FSHR and ZsGreen should be coexpressed in cells as two distinct proteins via ribosomal skipping driven by the P2A sequence, with the former faithfully reporting the endogenous expression of the latter. The ZsGreen signal was unexpectedly observed in nearly all extragonadal tissues and cells examined. Even within the gonads, the reporter was more abundant in noncanonical FSH targets than in Sertoli or granulosa cells.