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Pregnancy and labor increase the capacity of human myometrial cells to secrete parathyroid hormone-related protein.

机译:怀孕和分娩会增加人类子宫肌层细胞分泌甲状旁腺激素相关蛋白的能力。

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Parathyroid hormone-related protein (PTHrP), a oncofetal gene product possessing smooth muscle relaxant properties, has been found in rat and human uterine smooth muscle cells (USMC) where it is postulated to regulate myometrial tone and/or blood flow. Studies investigating the gestational regulation of PTHrP in human USMC have not been performed. This study was conducted to determine if pregnancy alters the capacity of USMC to secrete or respond to PTHrP. USMC cultures were established from 8 hysterectomy specimens (H) and 7 non-laboring (NP) and 5 laboring term pregnant uterine biopsies (LP). PTHrP secretion was measured at baseline and in response to TGF-beta1 using a immunoradiometric assay. The USMC response to PTHrP was assessed by incubating cultures with human (1-34)PTHrP and measuring cellular cAMP by radioimmunoassay. We found that cultures from the groups did not differ with respect to basal PTHrP secretion. TGF-beta1, on the other hand, produced dose-dependent increases in secreted PTHrP in each group such that LP>NP>H at 12 hrs and LP>NP and H 24 hrs. Maximal responses were found at 24 hrs in cells treated with 10 ng/ml TGF-beta1 (LP: 2034+/-366 vs NP: 1485+/-427; H: 1250+/-202 fmol/mg). Incubation of cultures with PTHrP produced dose-dependent increases in cAMP production, with 10(-7) M increasing levels by 64%. Neither pregnancy nor labor significantly affected the cAMP response. These findings indicate that the human myometrium has the capacity to increase PTHrP secretion during pregnancy and labor through a TGF-beta-dependent pathway. Such findings are consistent with a role of PTHrP in enhancing uterine blood flow.
机译:甲状旁腺激素相关蛋白(PTHrP)是一种具有胎膜平滑肌特性的胎粪基因产物,已在大鼠和人子宫平滑肌细胞(USMC)中发现,据推测该蛋白可调节肌层张力和/或血流。尚未进行研究人类USMC中PTHrP的妊娠调节的研究。进行这项研究是为了确定怀孕是否会改变USMC分泌PTHrP或对PTHrP作出反应的能力。 USMC培养是从8例子宫切除标本(H)和7例非人工(NP)和5例分娩期子宫活检(LP)建立的。使用免疫放射分析法在基线和对TGF-beta1的响应下测量PTHrP分泌。 USMC对PTHrP的反应是通过将培养物与人(1-34)PTHrP孵育并通过放射免疫法测量细胞cAMP来评估的。我们发现,各组的文化在基础PTHrP分泌方面没有差异。另一方面,TGF-β1在每组中导致分泌的PTHrP剂量依赖性增加,使得LP> NP> H在12小时时,LP> NP和H在24小时时。在用10 ng / ml TGF-beta1处理的细胞中,在24小时发现最大反应(LP:2034 +/- 366 vs NP:1485 +/- 427; H:1250 +/- 202 fmol / mg)。用PTHrP孵育培养物可产生剂量依赖性cAMP产生的增加,其中10(-7)M的水平增加64%。怀孕和分娩均未显着影响cAMP反应。这些发现表明,人子宫肌层具有通过TGF-β依赖性途径在妊娠和分娩过程中增加PTHrP分泌的能力。这些发现与PTHrP在增强子宫血流中的作用一致。

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