Bruno J F, Xu Y, Berelowitz M
Department of Medicine, SUNY at Stony Brook 11794.
Biochem Biophys Res Commun. 1994 Aug 15;202(3):1738-43. doi: 10.1006/bbrc.1994.2136.
Homologous up-regulation of somatostatin receptors (SSTR) was investigated in the GH3 clonal pituitary cell line. We report that chronic exposure to SRIF which has high affinity for all SSTR subtypes leads to a net increase in receptor binding and SSTR subtype mRNA. Treatment of cells with 1 microM SRIF increased specific [125I-Tyr11]SRIF binding to 280% of control values by 24 hr and to 350% by 48hr. Associated with the increase in SSTR binding was a net increase in SSTR subtype mRNA expression. Levels of SSTR1 increased to over 400% of control values by 6 hr and remained elevated for up to 48 hr. SSTR3, SSTR4, and SSTR5 mRNA was also dramatically increased at 24 and 48 hr. SSTR2 mRNA, in contrast, showed a biphasic response, initially increasing to 150% of control at 2 hr then decreasing to 50% at 6 hr with normalization by 48 hr. Our data suggests that multiple mechanisms contribute to the highly regulated expression of SSTR subtypes. The identification of specific molecular and cellular mechanisms mediating homologous SSTR up-regulation in GH3 cells and the involvement this process has in mediating the diverse biological effects of somatostatin are topics of current research.
在GH3克隆垂体细胞系中研究了生长抑素受体（SSTR）的同源性上调。我们报告，长期暴露于对所有SSTR亚型具有高亲和力的生长抑素释放抑制因子（SRIF）会导致受体结合和SSTR亚型mRNA的净增加。用1微摩尔SRIF处理细胞24小时后，特异性[125I-酪氨酸11]SRIF结合增加至对照值的280%，48小时后增加至350%。与SSTR结合增加相关的是SSTR亚型mRNA表达的净增加。SSTR1水平在6小时内增加至对照值的400%以上，并在长达48小时内保持升高。SSTR3、SSTR4和SSTR5 mRNA在24小时和48小时时也显著增加。相比之下，SSTR2 mRNA表现出双相反应，最初在2小时时增加至对照的150%，然后在6小时时降至50%，48小时时恢复正常。我们的数据表明，多种机制促成了SSTR亚型的高度调节表达。介导GH3细胞中SSTR同源性上调的特定分子和细胞机制的鉴定以及该过程在介导生长抑素的多种生物学效应中的作用是当前研究的课题。
