van Wijk P A, van Neck J W, Rijnberk A, Croughs R J, Mol J A
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Mol Cell Endocrinol. 1995 Apr 28;111(1):13-9. doi: 10.1016/0303-7207(95)03541-e.
In pituitary-dependent hyperadrenocorticism (Cushing's disease), the disturbed regulation of ACTH secretion is associated with neoplastic transformation of corticotropic cells. As these two phenomena are almost indissolubly connected, it is of prime importance to elucidate the factor(s) that induce corticotropic cell proliferation. Here we report on the effects of hypophysiotrophic hormones and intrapituitary growth factors on the proliferation and hormone secretion of the murine corticotropic tumour cell line AtT20/D16v, as measured by DNA content, and ACTH concentration in culture media. In addition, sensitivity to the inhibitory effect of cortisol was assessed under various conditions. Corticotropin releasing hormone (CRH) and vasopressin (AVP) induced proliferation of AtT20-cells. In contrast to that caused by AVP, the CRH-induced proliferation was associated with increased ACTH secretion, which could be inhibited by cortisol. Insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) also stimulated the proliferation of AtT20-cells. The proliferation of AtT20-cells was significantly inhibited by cortisol in all tests. The IGF-I-induced proliferation was the least sensitive to inhibition by cortisol. The growth factors did not stimulate ACTH secretion but IGF-I differed in that it prevented the inhibition of basal ACTH secretion by cortisol. Additional experiments (Western ligand blot analysis) concerning the relative insensitivity of IGF-I induced proliferation to inhibition by cortisol revealed that IGF-I increased the concentration of a 29 kDa IGF binding protein (IGFBP) in the culture medium. The concentration of the 29 kDa IGFBP was slightly decreased by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)
在垂体依赖性肾上腺皮质增生症（库欣病）中，促肾上腺皮质激素（ACTH）分泌调节紊乱与促肾上腺皮质细胞的肿瘤性转化相关。由于这两种现象几乎紧密相连，阐明诱导促肾上腺皮质细胞增殖的因素至关重要。在此，我们报告了促垂体激素和垂体内生长因子对小鼠促肾上腺皮质肿瘤细胞系AtT20/D16v增殖和激素分泌的影响，通过DNA含量及培养基中ACTH浓度来测定。此外，还评估了在各种条件下对皮质醇抑制作用的敏感性。促肾上腺皮质激素释放激素（CRH）和血管加压素（AVP）诱导AtT20细胞增殖。与AVP所致的增殖不同，CRH诱导的增殖与ACTH分泌增加相关，而皮质醇可抑制该分泌。胰岛素样生长因子-I（IGF-I）、表皮生长因子（EGF）和碱性成纤维细胞生长因子（bFGF）也刺激AtT20细胞增殖。在所有测试中，皮质醇均显著抑制AtT20细胞增殖。IGF-I诱导的增殖对皮质醇抑制最不敏感。生长因子未刺激ACTH分泌，但IGF-I不同，它可防止皮质醇对基础ACTH分泌的抑制。关于IGF-I诱导的增殖对皮质醇抑制相对不敏感的额外实验（Western配体印迹分析）显示，IGF-I增加了培养基中一种29 kDa胰岛素样生长因子结合蛋白（IGFBP）的浓度。皮质醇使29 kDa IGFBP的浓度略有降低。（摘要截短于250词）
