Expression of GnRH receptor gene in human ectopic endometrial cells and inhibition of their proliferation by leuprolide acetate.
The present study was conducted to investigate whether GnRH-receptor (GnRH-R) gene is expressed in endometriosis ovarian implants and whether a GnRH-analogue (GnRH-a) may exert an effect on endometriosis cell proliferation in vitro. The presence of GnRH-R transcripts in ovarian endometriosis cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and further confirmed by Southern blot analysis. GnRH-R mRNA was detected in all the 13 samples examined. In contrast, GnRH-R transcripts were not detectable in endometriosis-free peritoneal tissue. In the second part of the study, endometriosis cells were cultured for 9 days with different doses of leuprolide acetate (ranging from 0 to 10(-5) M). In 4 out of 13 cases, a significant anti-proliferative effect was observed at doses of leuprolide acetate ranging from 10(-9) to 10(-5) M. In one case, a significant inhibition of cell proliferation was observed only at 10(-5) M leuprolide acetate concentration. In contrast, the GnRH-a did not affect cell growth, regardless of the expression of GnRH-R transcripts and the given doses, in the remaining 8 experiments. To date, this is the first evidence indicating that GnRH-R mRNA is expressed in human ovarian endometriomas. Moreover, the inhibition of endometriosis cell proliferation induced by the GnRH-a in vitro suggests that, at least in some cases, this compound might exert a direct effect on endometriosis lesions.
Borroni
R
R
II Department of Obstetrics and Gynecology, University of Milano, School of Medicine, Italy.
Di Blasio
A M
AM
Gaffuri
B
B
Santorsola
R
R
Busacca
M
M
Viganò
P
P
Vignali
M
M
D000328:Adult; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D015342:DNA Probes / Q000235:genetics; D004715:Endometriosis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D016729:Leuprolide / Q000494:pharmacology*; D010049:Ovarian Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics*
D015342:DNA Probes; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide