Overexpression and Functional Relevance of Somatostatin Receptor-1, -2, and -5 in Endometrium and Endometriotic Lesions

摘要

Context: Somatostatin plays a role in physiological and pathological cell proliferation and angiogenesis. Five subtypes of somatostatin receptors have been identified, and the therapeutic use of somatostatin receptor-selective agonists has been reported in several diseases.Objectives: The aim was to describe the expression and the functional relevance of three human somatostatin receptors (sst_(1), sst_(2), and sst_(5)) in tissues of women with and without endometriosis.Patients and Methods: This pilot study analyzed endometrium, ovarian endometriomata, and peritoneal lesions in 15 patients affected by endometriosis and the endometrium of five women without endometriosis. ~(111)In-pentetreotide scintigraphy was used to detect endometriotic lesions; real-time RT-PCR and immunohistochemistry for sst_(1), sst_(2), and sst_(5) were performed. Migration and proliferation assays were performed on human endometrial stromal cells (ESC) treated with somatostatin and octreotide for 48 h.Results:~(111)In-pentetreotide scintigraphy was able to correctly identify and locate pelvic endometriotic lesions as confirmed by computed tomography scans. The endometrium of women with endometriosis expressed significantly more sst_(1), sst_(2), and sst_(5) in comparison to that of control women. Moreover, sst_(1), sst_(2), and sst_(5) were highly expressed in ovarian endometriomata and peritoneal lesions. The sst receptor ligand octreotide significantly inhibited ESC migration and proliferation with a maximum effect at 10~(?6)m, whereas somatostatin was effective only on ESC growth.Conclusions: This is the first report characterizing the overexpression and functional relevance of somatostatin receptors in eutopic endometrium and lesions of patients affected by endometriosis. Thus, the use of these receptors may provide new strategies for the diagnosis and treatment of endometriosis.