GISNe - Anatomia, Farmacologia e Medicina Legale

SOMATOSTATIN ANALOGUES AND GHRH ANTAGONISTS INHIBIT ECTOPIC
ENDOMETRIAL CELL PROLIFERATION AND SURVIVAL
Marta Annunziata, Letizia Trovato, Fabio Settanni, Cristina Grande, Marco Camanni*, Francesco
Deltetto*, Ezio Ghigo, Riccarda Granata.
Molecular and Cellular Endocrinology Laboratory, Department of Internal Medicine, University of
Turin. *Valdese Hospital, Turin.
Endometriosis, the presence of endometrial cells outside the uterus, is a common estrogendipendent
disorder that results in pelvic pain and infertility. Ectopic endometrium (outside the
uterus) shows increased proliferation, impaired sensitivity to apoptosis, and different gene
expression profiling with respect to eutopic endometrium (inside the uterus). Somatostatin (SS) 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 while GHRH stimulates both normal and cancer cell growth and survival. These
extra-pituitary effects are mediated by a family of five somatostatin receptor subtypes (SSTR1 to 5)
and by the GHRH receptor (GHRH-R), particularly the splice variant 1 (SV1). Moreover GHRH
antagonists act as antiproliferative molecules in normal and tumoral cells. Interestingly, both
SSTR2 and GHRH expression have been shown in normal human endometrium.
Aim of this study was to investigate the expression of GHRH, SS and their receptors in ectopic
endometrium of patients with endometriosis. Moreover, to test whether SS analogues and GHRH
antagonists would exert inhibitory effect on ectopic endometrial cell proliferation and survival. RT-
PCR results showed SSTR2 and 5 mRNA and GHRH-R SV1 in ectopic endometrium (n=14).
Further, by real- time PCR, we found that SSTR2 and SSTR5 were significantly more expressed in
ectopic than in eutopic tissues. Importantly, the SS analogues Lantreotide and Octreotide dosedependently
reduced ectopic endometrial stromal cell (ESC) growth and survival. Noteworthy, also
GHRH antagonist JV-1-36 showed potent inhibitory effect on ESC proliferation and viability.
In conclusion, these findings suggest that SS analogues, as well as GHRH antagonists may be
useful molecules for preventing proliferation and survival of ectopic endometrial cells in patients
with endometriosis.