Estrogen Receptors (α and β) and 17β-Hydroxysteroid Dehydrogenase Type 1 and 2 in Thyroid Disorders: Possible In Situ Estrogen Synthesis and Actions

Abstract

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) ␣ and ␤ 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 ER␣ and ␤ 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 ER␣ and ␤ and 17␤-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. ER␣ labeling index, or percentage of cells immunopositive for ER␣, 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 ER␣ in normal thyroid glands. In papillary carcinoma, ER␣ 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. ER␤ immunoreactivity was detected in both follicular and C-cells of normal thyroid glands, including those in developing fetal thyroid glands. In addition, ER␤ immunoreactivity was detected in the nuclei of various thyroid lesions. But no significant correlations were detected between ER␤ labeling index and clinicopathological findings including age, menopausal status, gender, and/or histological type of thyroid lesions. 17␤-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 ER␣, may become more pronounced in neoplasms, particularly in papillary carcinoma arising in premenopausal women. Biological effects of estrogens are generally mediated through an initial interaction with the estrogen receptor (ER), a member of the superfamily of nuclear receptors. Identification of ER is an initial step in understanding the estrogenic effects on various

Practical Applications in Immunohistochemistry: Carcinomas of Unknown Primary Site

“…15,16 Furthermore, ER is expressed in a wide subset of carcinomas, including those primary to the endometrium and ovary, but also in ''unexpected'' sites, such as papillary carcinomas of the thyroid 17,18 and adnexal tumors of the skin. 19,20 Most important from a diagnostic standpoint, a significant number of primary lung adenocarcinomas (approximately 10%-20%) can also show positive immunostaining, although in general these tumors show only focal ER expression.…”

The relationship between thyroid nodules and uterine fibroids

“…It could be explained in two ways. First, human thyroid gland has both intracrine or paracrine estrogen responsiveness and in situ estrogen synthesis [19,20] as uterine fibroid has [21]. In previous studies about uterine fibroids, systemic E2 levels showed no difference between subjects with uterine fibroids and without [22][23][24].…”

Дисгормональні Стани Репродуктивної Системи В жінок Після Тиреоїдектомії Та радіойодтерапії З приводу Диференційованої Карциноми Щитоподібної Залози

“…Тому залишаєть-ся дискутабельним питання, чому в низці випад-ків диспластичні процеси поширюються не на всю молочну залозу, а тільки на певні ділянки. За да-ними дослідників [4,5], це пов'язано з дефіцитом гестагенів і чутливістю рецепторів до естрадіолу та прогестерону. Гормональний дисбаланс сприяє морфофункціональній перебудові молочних залоз, Практикуючому ендокринологу /To Practicing Endocrinologists/ і в частини жінок в умовах активації рецепторного апарата молочних залоз формуються патологічні зміни [6,7].…”