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. 2023 Feb 16:14:1095031.
doi: 10.3389/fendo.2023.1095031. eCollection 2023.

Inadequate detection of the FSHR complicates future research on extragonadal FSHR localization

Victoria N Tedjawirja  1 , Gerrit K J Hooijer  2 , C Dilara Savci-Heijink  2 , Kristina Kovac  3 , Ron Balm  1 , Vivian de Waard  3
Affiliations

Inadequate detection of the FSHR complicates future research on extragonadal FSHR localization

Victoria N Tedjawirja et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: Recently, follicle stimulating hormone (FSH) through interaction with its receptor (FSHR) has been proposed to play a role in postmenopausal osteoporosis and cardiovascular disease, rather than the loss of estrogen. To explore this hypothesis, unravelling which cells express extragonadal FSHR on protein level is key.

Methods: We used two commercial anti-FSHR antibodies and validated them by performing immunohistochemistry on positive (ovary, testis) and negative controls (skin).

Results: The monoclonal anti-FSHR antibody could not identify the FSHR in ovary or testis. The polyclonal anti-FSHR antibody stained the granulosa cells (ovary) and Sertoli cells (testis), yet there was equally intense staining of other cells/extracellular matrix. Furthermore, the polyclonal anti-FSHR antibody also stained skin tissue extensively, suggesting that the antibody stains more than just FSHR.

Discussion: The findings in this study may add accuracy to literature on extragonadal FSHR localization and warrants attention to the use of inadequate anti-FSHR antibodies to value the potential role of FSH/FSHR in postmenopausal disease.

Keywords: antibodies; control; extragonadal cells; follicle stimulating hormone receptor; immunohistochemistry.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical analysis of FFPE human premenopausal ovary, testis and skin tissue (A–C, respectively). Polyclonal anti-FSHR antibody was ommitted (A1, B1 and C1) or the sections were incubated with the antibody (A2-3, B2-4, C2-3 in 1:500 dilution). Sections that were not incubated with the anti-FSHR antibody only showed blue nuclear staining. The asterisks show FSHR positive (red/brown) granulosa cells (A3) and possibly FSHR positive Sertoli cells among other positive cells in the seminiferous tubules of the testis (B3, B4). Staining inhibin in ovary tissue reveals how specific granulosa staining can be (A4). Staining of skin tissue with anti-cytokeratin 17 antibody shows specific staining of a hair follicle with its sebaceous gland (C4), as opposed to the aspecific staining throughout the skin tissue section by the anti-FSHR antibody. Magnification: Panels A1-2, B1-2, and C1-2 12.5x; Panels A3-4, B3-4, and C3-4 200x; Panel C4 100x.
Figure 2
Figure 2
Crystallographic image of the extracellular domain of the FSHR (blue, beige, yellow) folding over its ligand FSH (orange), adapted from Jiang et al. (22). In yellow the beta strands/leucine-rich repeat domains in amino acid stretch C18-N187 are highlighted, against which the polyclonal anti-FSHR antibody MBS178821 is raised. The blue ribbon represent the amino acids that exon 9 codes for, which lacks in the short FSHR variant.
See this image and copyright information in PMC

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