ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P611

Endometriotic cell proliferation and survival are inhibited by somatostatin analogues and GHRH antagonists

Marta Annunziata1, Letizia Trovato1, Fabio Settanni1, Cristina Grande1, Davide Gallo1, Marco Camanni2, Francesco Deltetto2, Ezio Ghigo1 & Riccarda Granata1

1University of Turin, Torino, Italy; 2Valdese Hospital, Torino, Italy.

Somatostatin (SST) and growth hormone-releasing hormone (GHRH) are hypothalamic hormones that, respectively, inhibit and stimulate pituitary GH secretion. In addition, in peripheral tissues somatostatin and its analogues inhibit, whereas GHRH stimulates, both normal and cancer cell growth and survival. Furthermore, both somatostatin receptor 2 (SSTR-2) and GHRH expression have been shown in normal human endometrium. Endometriosis is a common estrogen-dependent disorder defined by the presence of endometrial cells outside the uterus, resulting in pelvic pain and infertility. With respect to eutopic endometrium, the ectopic shows higher local oestradiol bioavailability, abnormalities in gene expression, impaired sensitivity to apoptosis and increased cell proliferation.

Aim of this study was to investigate the expression of GHRH and SST receptors in ectopic endometrium of patients with endometriosis and to test whether SST analogues and GHRH antagonists would inhibit in vitro proliferation and survival of primary endometrial cells obtained from endometriotic implants. In ectopic endometria (n=18) RT-PCR experiments showed the expression of all five somatostatin receptor subtypes (SSTR1 to 5), and of the splice variant-1 (SV1) of the GHRH-receptor (GHRH-R). By Real-time PCR we found that in 64% of patients SSTR2 and SSTR5 were significantly more expressed in ectopic than in eutopic tissues. Importantly, the SST analogues Lanreotide and Octreotide dose-dependently reduced ectopic more than eutopic endometrial cell growth and survival. Noteworthy, GHRH antagonist JV-1-36 showed significant inhibitory effect on stromal endometrial cell proliferation and viability.

In conclusion, these findings suggest that SST analogues, as well as GHRH antagonists, may be useful molecules for inhibiting proliferation and survival of ectopic endometrial cells in patients with endometriosis.

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