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Role of thyroid stimulating hormone in the maintenance and functioning of the human corpus luteum

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Abstract

Purpose

To evaluate the impact of high thyroid stimulating hormone (TSH) levels on human granulosa–luteal (hGL) cells.

Methods

hGL cells were isolated from follicular aspirates derived from patients undergoing IVF treatment without any thyroid disorder (serum TSH 0.5–2 mU/L). Cells were cultured at 37 °C in DMEM, supplemented with 5% FBS. The cells were treated with 1 nM LH and increasing concentrations of TSH. At the end of culture, conditioned medium and cells were collected to analyze progesterone production, cell viability, and mRNA levels of genes involved in the steroidogenesis process. Human ovarian tissues were analyzed for TSH receptor (TSHR) expression by IHC.

Results

The expression of TSHR was detected in human corpus luteum by IHC and in hGL by RT-PCR. In hGL cells, TSH treatment did not modulate progesterone production nor the expression of steroidogenic genes, such as p450scc and HSD3b 1/2. However, TSH induced a dose-dependent increase in cell death. Finally, TSH did not affect LH-induced p450scc and HSD3b1/2 expression while LH partially reverted TSH negative effect on cell death in hGL.

Conclusions

Elevated TSH levels in hypothyroid women may be associated with impaired CL functioning and maintenance. These findings open a new line of research for the importance of the treatment of women with thyroid dysfunction that could contribute to the onset of infertility.

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Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

We are grateful to Stefania Fera and Tiziana Biscetti for excellent technical support.

Funding

This study was supported by Ateneo Sapienza Funds to R. C. and Ministry of Research MIUR Grant PRIN 2017 2017TK7Z8L to EV.

Author information

Author notes

  1. M. Taggi & G. Saturno

    Present address: IVIRMA Global Research Alliance, GENERA, Clinica Valle Giulia, Rome, Italy

Authors and Affiliations

  1. DAHFMO, Unit of Histology and Medical Embryology, Sapienza, University of Rome, Rome, Italy

    M. Taggi, C. Capponi, N. Bertani, G. Saturno, R. Canipari & E. Vicini

  2. IVIRMA Global Research Alliance, GENERA, Clinica Valle Giulia, Rome, Italy

    F. Innocenti, L. Dovere, S. M. Fabozzi, D. Cimadomo, R. Mazzilli, L. Rienzi & F. M. Ubaldi

  3. Department Tutela della Salute della Donna, del Bambino e di Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy

    O. Alesiani & R. Apa

  4. Department of Woman and Child Health and Public Health, Area of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    V. Arena

  5. Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

    R. Mazzilli

  6. Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Urbino, Italy

    L. Rienzi

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  1. M. Taggi
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Contributions

DC, RM, LR, FMU, RC, EV,RA contributed to the study conception and design; material collection was performed by FI, LD, SMF; methodology: MT, CC, NB, GS, OA and VA; formal analysis and investigation: MT, CC, RC, EV; supervision: RC, EV; writing—original draft preparation MT; writing—review and editing: RC and EV; all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to R. Canipari or E. Vicini.

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The authors have no relevant financial or non-financial interests to disclose.

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Institutional review board approval to the study was obtained.

Research involving human participants and/or animals

The present study complies with the guidelines for human studies.

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All patients consented to the anonymous donation of waste material of IVF.

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Taggi, M., Capponi, C., Bertani, N. et al. Role of thyroid stimulating hormone in the maintenance and functioning of the human corpus luteum. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-023-02269-z

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