PARATHYROID-HORMONE AND PARATHYROID HORMOME-RELATED PROTEIN STIMULATE ADENYLATE-CYCLASE IN HUMAN ENDOMETRIAL STROMAL CELLS

PARATHYROID-HORMONE AND PARATHYROID HORMOME-RELATED PROTEIN STIMULATE ADENYLATE-CYCLASE IN HUMAN ENDOMETRIAL STROMAL CELLS
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DOI:
10.1111/j.1749-6632.1994.tb21767.x
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发表时间:
1994-01-01
期刊:
HUMAN ENDOMETRIUM
影响因子:
--
通讯作者:
MACDONALD, PC
MACDONALD, PC
中科院分区:
其他
文献类型:
--
作者:
CASEY, ML;ERK, A;MACDONALD, PC

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近年来,人们对血管活性蛋白在人类子宫内膜功能中的作用产生了相当大的兴趣。内皮素-1(ET-1)和甲状旁腺素相关蛋白(PTH-rP)是人子宫内膜产生的两种强有力的血管收缩剂和血管扩张剂。ET-1的生物合成和降解以及PTH-rP的生物合成也受到卵巢类固醇激素的调节。其中,分泌晚期和月经期子宫内膜中preproET-1 mRNA的表达水平较增殖期和分泌早中期升高。金属蛋白酶,脑啡肽酶,降解ET-1和其他小的,生物活性肽,在月经周期的中期分泌阶段,当血浆孕酮水平高时,其比活性最高。在单层培养的人子宫内膜间质细胞中,孕激素可使脑啡肽酶的比活性、脑啡肽酶蛋白水平和脑啡肽酶mRNA水平升高。另一方面,雌激素在人子宫内膜间质细胞中起作用,增加PTH-rP mRNA的水平,以及免疫反应性PTH-rP蛋白的水平。这两种血管活性蛋白的组织水平的调节还有其他共同的机制。转化生长因子-β 1(TGF-β 1)与其他细胞类型一样,可增加子宫内膜间质细胞中ET-1前体mRNA的水平。5. TGF-β在子宫内膜间质细胞中的作用是降低脑啡肽酶的比活性和脑啡肽酶免疫反应蛋白的水平。6 TGF-β 1还在子宫内膜基质细胞2和其他细胞类型7中起作用,以增加PTH-rP mRNA和免疫反应性和生物活性PTH-rP蛋白的水平。
In recent years, there has been appreciable interest in the role of vasoactive proteins in human endometrial function. Endothelin-1 (ET-l), a potent vasoconstrictor, and parathyroid hormone-related protein (PTH-rP), a vasodilator, are produced in human end~ metrium.'-~ Evidence also has been presented that the biosynthesis and degradation of ET-1 as well as the biosynthesis of PTH-rP are regulated by ovarian steroid hormones. Specifically, the levels of preproET-1 mRNA in endometrium during late secretory phase and during menses are increased compared with that in the proliferative and early/mid-secretory phases.'The specific activity of the metalloproteinase, enkephalinase, which degrades ET-1 and other small, bioactive peptides, is highest at mid-secretory phase of the menstrual cycle when plasma progesterone levels are high. In human endometrial stromal cells in monolayer culture, the specific activity of enkephalinase, the level of enkephalinase protein, and the level of enkephalinase mRNA are increased in response to pr~ gestin.~ On the other hand, estrogen acts in human endometrial stromal cells to increase the levels of PTH-rP mRNA, as well as immunoreactive PTH-rP protein^.^There are other common mechanisms for regulation of the tissue levels of these two vasoactive proteins. Transforming growth factor-p1 (TGF-P1) acts to increase the levels of preproET-1 mRNA in endometrial stromal cells' as in other cell types. 5 Furthermore, TGF-P acts in endometrial stromal cells to decrease the specific activity of enkephalinase, as well as the level of immunoreactive enkephalinase protein. 6 TGF-/31 also acts in endometrial stromal cells2 and in other cell types7 to increase the levels of PTH-rP mRNA and immunoreactive and bioactive PTH-rP protein.