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

Autor: DiMauro A; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA., Seger C; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA., Minor B; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA., Amitrano AM; Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA., Okeke I; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA., Taya M; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA., Rackow AR; Department of Environmental Medicine and Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, NY, USA., Kumar D; Division of Reproductive Endocrinology and Infertility, University of Rochester Medical Center, Rochester, NY, USA., Kottman RM; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA.; Division of Pulmonary Medicine, University of Rochester Medical Center, Rochester, NY, USA., Bhagavath B; Division of Reproductive Endocrinology and Infertility, University of Rochester Medical Center, Rochester, NY, USA., Hammes SR; Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Ave, Box 693, Rochester, NY, 14642, USA. Stephen_hammes@urmc.rochester.edu.
Jazyk: angličtina
Zdroj: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2022 Sep; Vol. 29 (9), pp. 2525-2535. Date of Electronic Publication: 2021 Nov 01.
DOI: 10.1007/s43032-021-00741-w
Abstrakt: 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.
(© 2021. Society for Reproductive Investigation.)
Databáze: MEDLINE
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