Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium.

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This study demonstrates that human endometrial glandular cells express functional FSH and LH receptors, which mediate intracellular signaling through dose-dependent cAMP increases and steroidogenic gene induction.

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This study investigated the presence and function of follicle-stimulating hormone (FSH) and luteinizing hormone/choriogonadotrophin (LH/hCG) receptors in human endometrial tissue. Researchers analyzed endometrial samples from healthy patients using RT-PCR, sequencing, and immunohistochemistry to confirm receptor expression, followed by in vitro treatments with recombinant hormones to assess intracellular signaling. The results demonstrated that both FSH and LH/hCG receptors are expressed on the membrane of endometrial gland cells and mediate dose-dependent increases in cyclic AMP and steroidogenic gene expression. This paper is centrally about endometriosis research context, as it establishes a physiological mechanism in normal endometrium relevant to understanding hormonal influences on ectopic endometrial-like tissue, though it does not directly study endometriosis lesions.

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Abstract

PurposeFollicle-stimulating hormone (FSH) and luteinizing hormone (LH) mediate intracellular functions by binding their specific protein G-coupled gonadotrophin receptor, respectively FSH receptor (FSHR) and LH/choriogonadotrophin receptor (LHCGR). Whereas the expression of FSHR and LHCGR in mammals was considered gonad-specific and cell-specific, studies identified gonadotrophin receptors in human female extragonadal reproductive tissues. This study aims to demonstrate that gonadotrophin receptors are expressed in endometrium and mediates intracellular functions.MethodsCollected endometria (n = 12) from healthy patients (mean age of 36 ± 6) were primary cultured for 24 h. The presence of gonadotrophin receptors was evaluated by RT-PCR followed by the sequencing of the resulted amplicons and by immunohistochemistry in original samples. Endometrial primary cultures were treated with increasing concentration (range 0-100 ng/ml) of either recombinant human LH (rhLH) or recombinant human FSH (rhFSH). Endometria controls had gonadotrophin replaced by the same volume of the culture medium. In gonadotrophin-treated samples, it was evaluated the intracellular cyclic adenosine monophosphate (cAMP) content by enzymatic immunoassay and the expression of steroidogenic genes by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).ResultsThe sequencing of the RT-PCR amplicons confirmed the presence of both gonadotrophin receptors and immunohistochemistry localized them on the membrane of endometrial glands cells throughout the glandular epithelium. The gonadotrophin-receptor complex was able to increase the intracellular cAMP in a dose-response and time-course manner and to induce steroidogenic genes expression.ConclusionThis study demonstrates that both gonadotrophin receptors are expressed along the glandular epithelium of endometria and they mediate the effects of gonadotrophins on intracellular functions.
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Abstract

Purpose Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) mediate intracellular functions by binding their specific protein G-coupled gonadotrophin receptor, respectively FSH receptor (FSHR) and LH/choriogonadotrophin receptor (LHCGR). Whereas the expression of FSHR and LHCGR in mammals was considered gonad-specific and cell-specific, studies identified gonadotrophin receptors in human female extragonadal reproductive tissues. This study aims to demonstrate that gonadotrophin receptors are expressed in endometrium and mediates intracellular functions.

Methods

Collected endometria (n = 12) from healthy patients (mean age of 36 ± 6) were primary cultured for 24 h. The presence of gonadotrophin receptors was evaluated by RT-PCR followed by the sequencing of the resulted amplicons and by immunohistochemistry in original samples. Endometrial primary cultures were treated with increasing concentration (range 0–100 ng/ml) of either recombinant human LH (rhLH) or recombinant human FSH (rhFSH). Endometria controls had gonadotrophin replaced by the same volume of the culture medium. In gonadotrophin-treated samples, it was evaluated the intracellular cyclic adenosine monophosphate (cAMP) content by enzymatic immunoassay and the expression of steroidogenic genes by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).

Results

The sequencing of the RT-PCR amplicons confirmed the presence of both gonadotrophin receptors and immunohistochemistry localized them on the membrane of endometrial glands cells throughout the glandular epithelium. The gonadotrophin-receptor complex was able to increase the intracellular cAMP in a dose-response and time-course manner and to induce steroidogenic genes expression.

Conclusion

This study demonstrates that both gonadotrophin receptors are expressed along the glandular epithelium of endometria and they mediate the effects of gonadotrophins on intracellular functions. Similar content being viewed by others

References

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Experimental evidence suggests prolonged exposure to hCG is detrimental to endometrial receptivity. Hum Reprod. 2013;28(6):1610–9. Acknowledgments We are deeply grateful to Prof. Franchini Antonella (Life Science Department of the University of Modena and Reggio Emilia) for her patience, advices, and in providing assistance with the samples preparation for immunohistochemistry and to Prof. Malagoli Davide (Life Science Department of the University of Modena and Reggio Emilia) for providing the IPLB-LdFB Lymantria dispar (Lepidoptera) cell line. Author information Authors and Affiliations Corresponding author Ethics declarations Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study. Conflict of interest The authors declare that they have no conflict of interest. Electronic supplementary material ESM 1 (download DOCX ) Lines 1–6 refer to samples of original endometria recovered from six different patients. M, DNA standard ladder (DOCX 274 kb) Rights and permissions About this article Cite this article Sacchi, S., Sena, P., Degli Esposti, C. et al. Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium. J Assist Reprod Genet 35, 1703–1712 (2018). https://doi.org/10.1007/s10815-018-1248-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-018-1248-8

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