Zatelli M C, Rossi R, del Senno L, degli Uberti E C
Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Italy.
Steroids. 1998 May-Jun;63(5-6):243-5. doi: 10.1016/s0039-128x(98)00027-0.
We have previously found that the androgen receptor gene is expressed both in normal and adenomatous human adrenal cortex and in the NCI-H295 human adrenocortical cancer cell line. Furthermore, we have observed that dihydrotestosterone (DHT) at physiological concentrations (10(-11) M) inhibits human adrenocortical cell growth in vitro and slightly decreases c-myc RNA levels in NCI-H295 cells. As c-myc is probably not the main mechanism mediating DHT-induced inhibition of cell growth, other genes controlling cell proliferation may be involved. Transforming Growth Factor beta (TGF beta) is a regulatory peptide that acts by both autocrine and paracrine mechanisms to control proliferation and differentiation, and there is previous evidence that TGF beta may exert an antimitotic effect on human fetal adrenal cells in vitro. This study examines a possible role for TGF beta 1 in mediating the DHT-induced reduction of human adrenocortical cell growth. TGF beta 1 and its receptor (TGF beta RII) are expressed in DHT-treated and nontreated NCI-H295 cells; on Northern blot analysis 24-h treatment with DHT (10(-11) M) produced a small increase in TGF beta RII RNA, and quantitative RT-PCR showed a 1.5-fold increase in TGF beta 1 RNA levels. These findings suggest that TGF beta 1 and its receptor may be involved in DHT-induced inhibition of human adrenocortical cell growth.
我们之前发现，雄激素受体基因在正常和腺瘤性人类肾上腺皮质以及NCI-H295人肾上腺皮质癌细胞系中均有表达。此外，我们观察到生理浓度（10⁻¹¹ M）的双氢睾酮（DHT）在体外可抑制人肾上腺皮质细胞生长，并使NCI-H295细胞中的c-myc RNA水平略有下降。由于c-myc可能不是介导DHT诱导的细胞生长抑制的主要机制，其他控制细胞增殖的基因可能也参与其中。转化生长因子β（TGFβ）是一种调节肽，通过自分泌和旁分泌机制发挥作用来控制细胞增殖和分化，并且之前有证据表明TGFβ在体外可能对人胎儿肾上腺细胞发挥抗有丝分裂作用。本研究探讨了TGFβ1在介导DHT诱导的人肾上腺皮质细胞生长减少中的可能作用。TGFβ1及其受体（TGFβRII）在DHT处理和未处理的NCI-H295细胞中均有表达；Northern印迹分析显示，用DHT（10⁻¹¹ M）处理24小时后，TGFβRII RNA略有增加，定量RT-PCR显示TGFβ1 RNA水平增加了1.5倍。这些发现表明，TGFβ1及其受体可能参与了DHT诱导的人肾上腺皮质细胞生长抑制。
