Transitional cell
metaplasia (TCM) of the uterine cervix and vagina is typically seen in patients with
adrenogenital syndrome with high serum
androgen levels and in those under
androgen treatment as well as in some peri/postmenopausal women. Considering that TCM occurs in patients with increased serum
androgen levels, a microenvironment with altered
sex hormones might be involved in the urothelial-like differentiation observed in TCM. To investigate a histogenetic role of
androgen in TCM development, we compared the distribution patterns and intensity of
androgen receptor (AR),
estrogen receptor (ER), GATA3 (a
transcription factor involved in
androgen regulation), Ki-67, and AKR1C3 (an
enzyme involved in
androgen biosynthesis) expression in normal exocervical mucosa in young women (n = 25), senile
atrophy (n = 23), and TCM (n = 29). In TCM, AR, ER, AKR1C3, and GATA3, expression was stronger and significantly increased upward into the intermediate and superficial layers compared with the senile atrophic mucosa and normal mucosa in young women. The epithelial layer in TCM is thicker than that in senile atrophic mucosa, although both conditions may occur in the same age group. Proliferation in TCM was significantly lower than that in young women but slightly higher than that in senile
atrophy. Considering the conversion activity of AKR1C3, thicker epithelial layers in TCM compared with those in senile
atrophy might be due to increased conversion of
androstenedione to
testosterone via increased AKR1C3 activity, increased conversion of
testosterone to 17β-estradiol by aromatization, and AR activation.