HUMAN MYOMETRIAL SMOOTH-MUSCLE CELLS ARE NOVEL TARGETS OF DIRECT REGULATION BY HUMAN CHORIONIC-GONADOTROPIN
HUMAN MYOMETRIAL SMOOTH-MUSCLE CELLS ARE NOVEL TARGETS OF DIRECT REGULATION BY HUMAN CHORIONIC-GONADOTROPIN
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DOI：
10.1095/biolreprod49.6.1149
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发表时间：
1993-12-01
影响因子：
3.6
通讯作者：
RAO, CV
中科院分区：
文献类型：
--
作者：
KORNYEI, JL;LEI, ZM;RAO, CV
人子宫肌层含有hCG/人LH（hLH）受体。这表明hCG和hLH可能调节人子宫肌层，而子宫肌层以前并不被认为是促性腺激素调节的直接靶点。为了研究这种可能性，从非妊娠人子宫肌层中分离出高纯度和活的平滑肌细胞，并培养成单层细胞。这些细胞含有hCG/LH受体mRNA转录物和一种50 kDa的免疫反应性蛋白，该蛋白可以以配体特异性方式结合I-125-hCG。培养过程中hCG的存在导致子宫肌层平滑肌细胞密度显著增加。hCG的作用是时间和浓度依赖性的，并模仿hLH，但不是由人FSH或人促甲状腺激素。人CG也大大增加了子宫肌层平滑肌细胞亚群的大小，而不影响其染色体倍性。hCG/LH受体和hCG的抗体阻断hCG的作用。不与hCG/LH受体结合的人催乳素和生长激素也增加了子宫肌层平滑肌细胞密度。蛋白激酶A抑制剂（H-89）阻断hCG反应，而calphostin（蛋白激酶C抑制剂）和laviustin A（酪氨酸激酶抑制剂）对hCG反应没有影响，表明cAMP/蛋白激酶A信号传导机制参与hCG作用。花生四烯酸代谢的环氧合酶和5-脂氧合酶途径的类花生酸可能不参与，因为这些酶的抑制剂对hCG反应没有影响。虽然孕酮和雌二醇不能减少或改变hCG的作用，但表皮生长因子确实能模拟hCG增加子宫肌层平滑肌细胞密度，总之，我们的结果表明hCG可直接调节子宫肌层平滑肌细胞，引起增生和肥大。
Human myometrium contains receptors for hCG/human LH (hLH). This suggested the possibility that hCG and hLH might regulate human myometrium, which has not previously been considered a direct target of gonadotropin regulation. To investigate such a possibility, highly pure and viable smooth muscle cells were isolated from nonpregnant human myometrium and cultured as monolayers. The cells contained hCG/LH receptor mRNA transcripts and a 50-kDa immunoreactive protein that can bind I-125-hCG in a ligand-specific manner. The presence of hCG during culture resulted in a significant increase of myometrial smooth muscle cell density. The hCG effect was time- and concentration-dependent and was mimicked by hLH but not by human FSH or human thyroid-stimulating hormone. Human CG also greatly increased the size of a subpopulation of myometrial smooth muscle cells without affecting their chromosomal ploidy. Antibodies to hCG/LH receptors and hCG blocked hCG effects. Human prolactin and growth hormone, which do not bind to hCG/LH receptors, also increased the myometrial smooth muscle cell density. A protein kinase A inhibitor (H-89) blocked hCG response whereas calphostin (a protein kinase C inhibitor) and lavendustin A (a tyrosine kinase inhibitor) had no effect on hCG response, suggesting that a cAMP/protein kinase A signaling mechanism is involved in hCG action. Eicosanoids from cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism are probably not involved, because the inhibitors of these enzymes had no effect on hCG response. While progesterone and estradiol could not minic or modify hCG action, epidermal growth factor did mimic hCG in increasing myometrial smooth muscle cell density.In summary, our results demonstrate that hCG can directly regulate myometrial smooth muscle cells, causing hyperplasia as well as hypertrophy.