Identification and quantification of dopamine receptor 2 in human eutopic and ectopic endometrium: a novel molecular target for endometriosis therapy.
Previous studies in an experimental mouse model of endometriosis have shown that the dopamine agonist (DA) cabergoline (Cb2) reduces angiogenesis and endometriotic lesions, hypothetically binding to the dopamine receptor type-2 (DRD2). To date, this has not been described in human endometrium and/or endometriotic lesions. Thus, we aimed to investigate the presence of DRD2 in said tissues. Endometrium fragments were implanted in nude mice treated with different doses of Cb2. Polymerase chain reaction assays and immunohistochemistry were performed to analyze the gene and protein expressions (respectively) of DRD2, VEGF, and VEGF receptor-2 (KDR). In addition, lesions and endometrium from women with mild and severe endometriosis and endometrium from healthy women were collected to analyze their gene expression profile. In experimental endometriosis, DRD2 was expressed at gene and protein levels in all three groups. VEGF gene and protein expressions were significantly lower in lesions treated with Cb2 than in controls. KDR protein expression was significantly lower in experimental lesions treated with Cb2 than in controls. In eutopic endometria, there was a significant decrease in DRD2 expression and an increase in VEGF in women with mild and severe endometriosis with respect to healthy patients. In endometriosis, KDR expression was significantly higher in red than in white and black lesions. VEGF expression was significantly lower in black than in red lesions. DRD2 is present in the human eutopic and ectopic endometrium and is regulated by DA, which provides the rationale for pilot studies to explore its use in the treatment of endometriosis.
Novella-Maestre
Edurne
E
Unidad de Genetica, Hospital Universitario La Fe, Valencia, Spain. edurnenovella@yahoo.es
Carda
Carmen
C
Ruiz-Sauri
Amparo
A
Garcia-Velasco
Juan A
JA
Simon
Carlos
C
Pellicer
Antonio
A
D000293:Adolescent; D000328:Adult; D000818:Animals; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D004873:Ergolines / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D018587:Oocyte Donation; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D042442:Vascular Endothelial Growth Factors; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077465:Cabergoline