Basic Research on Peptide Analogs

点击翻译按钮获取中文摘要

In this study, we investigated (1) the effect of various peptide analogs, especialy analogs of luteinizing hormone releasing hormone (LHRH) and somatostatin, on the growth of human ovarian cancer or endometrial cancer and (2) the effect of LHRH analogs on rat ovarian follicle development.High-affinity LHRH binding sites and mRNA for LHRH receptor were detected in HTOA human epithelial ovarian cancer cell line. LHRH agonist (buserelin) and antagonist (SB-75) inhibited the growth of HTOA tumors xenografted in athymic nude mice dose-dependently. LHRH analogs directly inhibited the proliferation of HTOA cells through apoptosis and interference with EGF receptor phosphorylation. High-affinity somatostatin binding sites and mRNA for somatostatin receptor were detected in HEC-1 human endometrial cancer cell line. Somatostatin analog (RC-160) also inhibited the growth of HEC-1 cells in vivo and in vitro. RC-160 suppressed EGF receptor phosphorylation, but did not induce apoptosis in HEC-1 cells.LHRH analogs directly inhibited the proliferation of rat granulosa cells through apoptosis without interference with EGF receptor phosphorylation. In estrogen-primed hypophysectomized immature female rats, mRNA for LHRH and LHRH receptor was detected in ovarian granulosa cells by non-radioactive in situ hybridization. LHRH agonist decreased follicular growth and increased atretic follicles. In contrast, when local LHRH was blocked by administration of LHRH antagonist, follicular growth was promoted and incidence of atresia was significantly decreased in secondary and tertiary follicles less than 200mum in diameter. These results support that the possibility that endogenous LHRH is involved in atresia of immature follicles.