Prolactin is Expressed in Uterine Leiomyomas and Promotes Signaling and Fibrosis in Myometrial Cells
Prolactin is Expressed in Uterine Leiomyomas and Promotes Signaling and Fibrosis in Myometrial Cells
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DOI：
10.1007/s43032-021-00741-w
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发表时间：
2021-11-01
影响因子：
2.9
通讯作者：
Hammes, Stephen R.
中科院分区：
文献类型：
--
作者：
DiMauro, Alessandra;Seger, Christina;Hammes, Stephen R.
子宫肌瘤是发生在子宫肌层的良性、雌激素敏感的纤维化平滑肌细胞肿瘤。平滑肌瘤是一个相当大的健康负担，终生患病率为 80%，且治疗选择有限。雌激素和孕激素对平滑肌瘤的生长具有积极作用，但人们对其他激素的作用知之甚少。一种令人感兴趣的激素是催乳素，因为它已被描述在平滑肌瘤中存在并发挥作用。目前的研究调查了平滑肌瘤内催乳素的产生及其对子宫肌层细胞的影响。相对于匹配的相邻子宫肌层，对人类平滑肌瘤样品进行 RNA 分离和定量 PCR 证实了催乳素和多巴胺受体 D2 的显着表达，催乳素受体 D2 是垂体中催乳素产生和释放的已知调节因子，而催乳素受体表达没有差异。免疫组织化学证实，与没有子宫肌瘤的女性的邻近子宫肌层和子宫相比，子宫肌瘤中的催乳素有所增加。这些结果表明，平滑肌瘤含有产生催乳素的细胞，催乳素可能会促进平滑肌瘤细胞中的信号传导，从而调节平滑肌瘤的发育/生长。因此，我们发现催乳素在大鼠和人子宫肌细胞系中强烈激活 STAT5 和 MAPK 信号传导。此外，催乳素刺激大鼠子宫肌细胞中肌成纤维细胞标志物的表达。我们的研究结果表明，平滑肌瘤中局部催乳素的产生可能刺激子宫肌层细胞向肌成纤维细胞的转分化，这反过来又促进了平滑肌瘤的纤维化性质。
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.