Estrogen receptors (α and β) and 17β-hydroxysteroid dehydrogenase Type 1 and 2 in thyroid disorders: Possible in situ estrogen synthesis and actions

Both epidemiological and experimental findings suggest the possible roles of sex steroids in the pathogenesis and/or development of various human thyroid disorders. In this study, we evaluated the expression of estrogen receptors (ER) α and β in normal thyroid glands (N = 25; female: n = 13, male: n = 10, unknown: n = 2) ranging in age from fetus to adult. Furthermore, using immunohistochemistry, we investigated the expression of ERα and β in 206 cases of thyroid disorders, including 24 adenomatous goiters, 23 follicular adenomas, and 159 thyroid carcinomas. In addition, we also studied the mRNA expression of ERα and β and 17β-hydroxysteroid dehydrogenase Type 1 and 2, enzymes involved in the interconversion between estrone and estradiol, using reverse transcription polymerase chain reaction (RT-PCR), in 48 of these 206 cases (10 adenomatous goiters, 10 follicular adenomas, and 28 papillary thyroid carcinomas) in which fresh frozen tissues were available for examination to further elucidate the possible involvement of intracrine estrogen metabolism and/or actions in thyroid disorders. ERα labeling index, or percentage of cells immunopositive for ERα, was significantly higher in adenomatous goiter (14.2 ± 6.4), follicular adenoma (13.4 ± 5.1), and thyroid carcinoma (16.4 ± 2.1) than in normal thyroid gland (0; P < .05). Few follicular cells were positive for ERα in normal thyroid glands. In papillary carcinoma, ERα labeling index was significantly higher in premenopausal women (28.1 ± 4.5) than in postmenopausal women (14.2 ± 2.9) and in men of various ages (7.6 ± 2.7; P < .05). In other histological types of thyroid carcinoma, no significant correlations were detected. ERβ immunoreactivity was detected in both follicular and C-cells of normal thyroid glands, including those in developing fetal thyroid glands. In addition, ERβ immunoreactivity was detected in the nuclei of various thyroid lesions. But no significant correlations were detected between ERβ labeling index and clinicopathological findings including age, menopausal status, gender, and/or histological type of thyroid lesions. 17β-hydroxysteroid dehydrogenase Type 1 expression was detected in 31/48 (64.0%) of the cases examined, whereas Type 2 was detected only in 3/46 (6.3%) of all the cases examined. These results demonstrated that estrogens may influence the development, physiology, and pathology of human thyroid glands, and these effects, especially through ERα, may become more pronounced in neoplasms, particularly in papillary carcinoma arising in premenopausal women.