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Prolactin is Expressed in Uterine Leiomyomas and Promotes Signaling and Fibrosis in Myometrial Cells

  • Reproductive Endocrinology: Original Article
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Abstract

Uterine leiomyomas are benign, estrogen-sensitive, fibrotic smooth muscle cell tumors occurring in the uterine myometrium. Leiomyomas are a considerable health burden, with a lifetime prevalence of 80% and limited treatment options. Estrogen and progesterone have positive effects on leiomyoma growth, but little is known about the roles of other hormones. One hormone of interest is prolactin, as it has been described to be present and functional in leiomyomas. The current study investigates prolactin production within leiomyomas and its effects on myometrial cells. RNA isolation and quantitative-PCR of human leiomyoma samples relative to matched adjacent myometrium confirms significant expression of prolactin and dopamine receptor D2, a known regulator of prolactin production and release in the pituitary, with no difference in prolactin receptor expression. Immunohistochemistry confirms increased prolactin in leiomyomas compared to adjacent myometrium and uteri from women without leiomyomas. These results suggest that leiomyomas contain cells that produce prolactin, which may then promote signaling in leiomyoma cells to regulate leiomyoma development/growth. Accordingly, we find that prolactin robustly activates STAT5 and MAPK signaling in rat and human myometrial cell lines. Furthermore, prolactin stimulates expression of myofibroblast markers in rat myometrial cells. Our findings suggest that local prolactin production in leiomyomas may stimulate trans-differentiation of myometrial cells to myofibroblasts, which in turn contributes to the fibrotic nature of leiomyomas.

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All data generated or analyzed during this study are included in this published article.

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Funding

NIH grant R01CA193583 (S.R.H.) funded the majority of this work. B.M. was supported by T32AI007285. B.B. was supported by the Richard W. and Mae Stone Goode Grant Program.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA

    Alessandra DiMauro, Christina Seger, Briaunna Minor, Ifunanya Okeke, Manisha Taya, R. Matthew Kottman & Stephen R. Hammes

  2. Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA

    Andrea M. Amitrano

  3. Department of Environmental Medicine and Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, NY, USA

    Ashley R. Rackow

  4. Division of Reproductive Endocrinology and Infertility, University of Rochester Medical Center, Rochester, NY, USA

    Divya Kumar & Bala Bhagavath

  5. Division of Pulmonary Medicine, University of Rochester Medical Center, Rochester, NY, USA

    R. Matthew Kottman

Authors
  1. Alessandra DiMauro
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  2. Christina Seger
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Contributions

A.D. performed the majority of the studies in this manuscript, wrote the initial draft of the manuscript, and created most of the figures. C.S., B.M. A.A., and I.O. also performed experiments presented in the manuscript. A.R.K. performed the prolactin-induced fibroblast factor studies. M.T. served as an advisor for these studies. B.B. came up with the concept and with help of D.K. provided the uterine samples. S.R.H. supervised the project and assisted with data interpretation and presentation, as well as writing of the manuscript.

Corresponding author

Correspondence to Stephen R. Hammes.

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The authors declare that they have no competing interests.

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All patients were provided informed consent. IRB and IACUC approval was obtained for this study. All samples were de-identified.

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All work was performed in the Hammes laboratory at the University of Rochester Medical Center. All authors consent for publication.

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DiMauro, A., Seger, C., Minor, B. et al. Prolactin is Expressed in Uterine Leiomyomas and Promotes Signaling and Fibrosis in Myometrial Cells. Reprod. Sci. 29, 2525–2535 (2022). https://doi.org/10.1007/s43032-021-00741-w

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  • DOI: https://doi.org/10.1007/s43032-021-00741-w

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