Effect of aromatase inhibitors on proliferation and apoptosis of endometriotic lesions

BILOTAS M; MERESMAN GF; STELLA I; SUELDO C; BARAÑAO RI

Buenos Aires, Argentina

Jornada; VIII Jornadas Multidisciplinarias de la Sociedad Argentina de Biología; 2006

Recent studies have shown that patients with endometriosis (EDT) have increased aromatase P450 expression in the endometrial tissue. The objective of this study was to evaluate the “in vivo” effect of aromatase inhibitors (Anastrozole=Ana and Letrozole=Let) on the implantation, proliferation and apoptosis of ectopic endometrial tissue. For this purpose we induced endometriotic lesions in 51 two months old female Balb/c mice. Animals were divided in 3 groups: Control (n=19), Ana (n=16) and Let (n=16). Treatments consisted of saline solution (control) or a daily s.c. injection of Ana or Let (10 mg/day). After 28 days of treatment (beginning on day 1 post- induction of EDT), lesions were measured, proliferation was evaluated by immunohistochemistry using anti-PCNA antibody, and percentages of apoptotic cells was determined using TUNEL technique. We observed that although percentages of animals that developed EDT and the number of lesions per animal were similar in all groups, the size of the endometriotic lesions was significantly smaller in Ana group (p< 0.05 vs. control) and in Let group (p<0.001 vs. control). Additionally we found that both Ana and Let treatments produced a significant decrease in cell proliferation (p<0.01 and p<0.001 vs. control respectively) and a significant increase in apoptosis (p<0.05 and p<0.01 vs. control respectively). In conclusion, the treatment of EDT with aromatase inhibitors in this animal model did not prevent the establishment of the lesions but significantly diminished the size of the lesions. Also, aromatase inhibitors inhibited cell proliferation in the EDT lesions and increased the degree of apoptosis. This data favors further investigation of aromatase inhibitors as a treatment for EDT.