Inverse correlation between thyroid peroxidase(TPO) and gamma-glutamyl transpeptidase(GGT) activities expressed in diisopropanolnitrosamine(DIPN) induced rat thyroid lesions. An enzyme histochemical study.

Abstract

The histochemical localization of thyroid peroxidase (TPO) and gammaglutamyl transpeptidase (GGT) in diisopropanolnitrosamine (DIPN) induced rat thyroid lesions was examined.The former was utilized as a marker of the endocrine function of the follicular epithelium and the latter as that of neoplastic growth.The two enzymes revealed an inverse correlation in their patterns of localization, i.e., TPO was positive in most of the benign nodular lesions and negative in malignant nodules, while GGT was positive in the nodules or areas of nodules which were negative for TPO.It is generally accepted that phenotypical alteration occurs in cells and tissues during carcinogenesis of various origins in association with functional retardation and elevated growth activity (2,3,10,18,20,24,25).In the thyroid gland, the activity of thyroid peroxidase (TPO), an essential enzyme of endocrine function (15), is known to decrease or to disappear during the course of tumorigenesis (4, 24). On the other hand, gamma-glutamyl transpeptidase (GGT) which is detected normally in the rat thyroid gland in the early stage of the fetal period, comes to be expressed in the malignant type of diisopropanolnitrosamine (DIPN) induced-rat thyroid lesions (12, 13).The present study was undertaken to investigate the precise correlation in the localization patterns between both enzymes by alternate detection of their activity in serial tissue sections from various stages of carcinogenesis. MATERIALS AND METHODSAnimals Twenty adult male Wistar strain rats of 100-150 g in body weight were injected subcutaneously with DIPN (diisopropanolnitrosamine, Nakarai Chemical Co.) at a dose of 750 mg per kg body weight weekly for 10 weeks. As controls, five rats were prepared and were injected with PBS (phosphate buffered saline) in the same manner. After the final injection, animals were sacrificed weekly by cardiac bleeding, 455

Cell proliferation and differentiation of cancerous and non-cancerous thyroid tissues of rats.

“…By the immunohistochemical stains for thyroglobulin, we recognized that the carcinoma lesion, both non-invasive and invasive parts, showed reduced expression of cytodifferentiation whereas epithelial cells in hyperplastic, regenerative, and normal thyroid tissues were positive for thyroglobulin. These findings are in good agreement with the previous reports of rat thyroid tumors (13,21).…”

Follicular Thyroglobulin (TG) Suppression of Thyroid-restricted Genes Involves the Apical Membrane Asialoglycoprotein Receptor and TG Phosphorylation

“…Each thyrocyte is faced with the same levels of TSH and insulin/IGF-1 in the blood stream, yet the functional state of each follicle varies (18,19,(51)(52)(53)(54). Some have high levels of TG and thyroid hormones in their follicular lumen, exhibit high levels of TPO activity, and are surrounded by metabolically active columnar epithelial cells; others are nearly devoid of TG, TPO, and thyroid hormones and are surrounded by flattened and quiescent thyroid cells (18,19,(51)(52)(53)(54).…”

“…Some have high levels of TG and thyroid hormones in their follicular lumen, exhibit high levels of TPO activity, and are surrounded by metabolically active columnar epithelial cells; others are nearly devoid of TG, TPO, and thyroid hormones and are surrounded by flattened and quiescent thyroid cells (18,19,(51)(52)(53)(54). Recent studies suggest that TG accumulated in the follicular lumen partially explains the heterogeneity of follicular function (17,18).…”

Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin

“…Indeed, significant follicular variability exists, not only in shape, size and colloid density, but also in the ability to accumulate iodide, diffusion of iodinated thyroglobulin (Tg) within the follicular lumen (Gerber et al 1985, 1986, Suzuki et al 1999c, levels of Tg and thyroid hormones within the follicles (Suzuki et al 1999a(Suzuki et al , 1999c, and even in expression of thyroid transcription factor (TTF-1), an essential transcription factor (Suzuki et al 1999a(Suzuki et al , 1999b. In addition, heterogeneity in the expression of other proteins and cell growth has been noted under various experimental conditions (Yamamoto et al 1988 and in human goiters (Peter et al 1985, Studer et al 1989.…”