Aromatase P450 (
P450arom) is the key
enzyme for the biosynthesis of
estrogen that is essential for the growth of human
endometriosis, a pathology characterized by endometrium-like tissue on the peritoneal surfaces of abdominal organs manifest by
pelvic pain and
infertility. Surgically transplanted autologous uterine tissue to ectopic sites on the peritoneum in mice has been used as an animal model to study
endometriosis. Using this mouse model, we evaluated the roles of the
P450arom gene and
aromatase enzyme activity in the growth of
endometriosis represented by ectopic uterine tissues in mice.
Endometriosis was induced surgically in the following groups of mice: 1) untreated transgenic mice with disrupted
P450arom gene (ArKO); 2) ArKO mice treated with systemic
estrogen; 3) untreated wild-type (WT) mice; 4) WT mice treated with
estrogen; 5) WT mice treated with the
aromatase inhibitor,
letrozole; and 6) WT mice treated with
letrozole and
estrogen. Each group contained eight mice; +/+ littermates of ArKO mice were used as WT controls. Treatment with
estrogen increased the size of ectopic uterine tissues in ArKO and WT mice significantly. The ectopic uterine lesions in untreated and
estrogen-treated ArKO mice were strikingly smaller than those in untreated and
estrogen-treated WT controls, respectively. Systemic treatment of WT mice with
letrozole significantly decreased the lesion size in a dose-dependent manner. The addition of
estrogen to
letrozole treatment increased the ectopic lesion size, although these lesions were significantly smaller than those in mice treated with
estrogen only. As tissue controls, the effects of these conditions on normally located (eutopic) uterine tissue were evaluated. The effects of disruption of the
P450arom gene and treatments with
letrozole and
estrogen seemed to be more profound on
ectopic tissues, suggesting that
ectopic tissues might be more sensitive to
estrogen for growth. We conclude that both an intact
P450arom gene and the presence of
aromatase enzyme activity are essential for the growth of ectopic uterine tissue in a mouse model of
endometriosis.