The Herbicide Metolachlor Induces Liver Cytochrome P450s 2B1/2 and 3A1/2, but Not Thyroxine-Uridine Dinucleotide Phosphate Glucuronosyltransferase and Associated Thyroid Gland Activity

2003 ◽  
Vol 22 (4) ◽  
pp. 287-295 ◽  
Author(s):  
Shana R. Dalton ◽  
Richard T. Miller ◽  
Sharon A. Meyer
Keyword(s):  
Thyroid Gland ◽  
Epithelial Cell ◽  
Thyroid Stimulating Hormone ◽  
Cytochrome P450s ◽  
Tumor Promoter ◽  
Sprague Dawley ◽  
Follicular Epithelial Cell ◽  
Rat Thyroid ◽  
Thyroid Gland Activity ◽  
Follicular Epithelial

Metolachlor (2-chloro- N-(2-ethyl-6-methylphenyl)- N-(2-methoxy-1-methylethyl) acetamide) is widely used internationally as a corn and cotton herbicide. The metolachlor effects noted in rats during testing for U.S. pesticide registration include increased liver weight and hepatocarcinogenicity associated with eosinophilic foci. These properties, plus nongenotoxicity, are also characteristic of the prototypical rat liver tumor promoter, phenobarbital. Phenobarbital induces hepatic cytochrome P450s CYP2B1/2 and CYP3A1/2 and thyroxine (T4)-UDP-glucuronosyltransferase (T4-UGT), which enhances thyroxine clearance and thus indirectly increases thyroid gland activity. Because other chloroacetanilide herbicides are known to similarly affect rat thyroid gland, this study tested the hypothesis that metolachlor would have these additional phenobarbital-like effects on liver, especially that of T4-UGT induction with consequential stimulation of thyroid gland. Effects of metolachlor, fed to male Sprague-Dawley rats for 14 days at the carcinogenic dose of 3000 ppm, were compared to those of equimolar phenobarbital. Liver microsomal CYP2B1/2 and CYP3A1/2 were probed by immunoblotting and T4-UGT was measured enzymat-ically. Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) and thyroid follicular epithelial cell morphology and proliferation were used to assess thyroid gland activity. Metolachlor induced CYP2B1/2 and CYP3A1/2 proteins, but unlike phenobarbital, did not affect T4-UGT activity. In agreement, serum T4, T3, or TSH were unaffected by metolachlor. Also, no significant effects of metolachlor on thyroid gland morphology or follicular epithelial cell height or proliferation were observed. These data demonstrate that metolachlor is an inducer of hepatic CYP2B1/2 activity. But unlike the prototypical CYP2B1/2 inducer phenobarbital, metolachlor does not cause an increase in T4-glucuronidation and thyroid gland activation.

scholarly journals Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (9) ◽  
pp. 2085-2092 ◽  
Author(s):  
Tomomi Kurashige ◽  
Yasuyo Nakajima ◽  
Mika Shimamura ◽  
Mutsumi Matsuyama ◽  
Masanobu Yamada ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Gene Knockout ◽  
Tissue Degeneration ◽  
Serum T4 ◽  
Follicular Epithelial Cell ◽  
Thyroid Morphology ◽  
And Function ◽  
Cellular Components ◽  
Follicular Epithelial

Abstract Autophagy is a catabolic process that involves the degradation of cellular components through the lysosomal machinery, relocating nutrients from unnecessary processes to more pivotal processes required for survival. It has been reported that systemic disruption of the Atg5 or Atg7 gene, a component of autophagy, is lethal and that its tissue-specific disruption causes tissue degeneration in several organs. However, the functional significance of autophagy in the thyroid glands remains unknown. Our preliminary data imply the possible involvement of dysfunctional autophagy in radiation-induced thyroid carcinogenesis. Therefore, we evaluated the effect of Atg5 gene knockout (KO) on thyroid morphology and function. To this end, Atg5flox/flox mice were crossed with TPO-Cre mice, yielding the thyroid follicular epithelial cell (thyrocyte)‒specific ATG5-deficient mice (Atg5thyr-KO/KO). Atg5 gene KO was confirmed by a lack of ATG5 expression, and disruption of autophagy was demonstrated by a decrease in microtubule-associated protein 1 light chain 3–II puncta and an increase in p62. Atg5thyr-KO/KO mice were born normally, and thyroid morphology, thyroid weights, and serum T4 and TSH levels were almost normal at 4 months. However, at 8 and 12 months, a decrease in the number of thyrocytes and an increase in TUNEL+-thyrocytes were observed in Atg5thyr-KO/KO mice even though thyroid function was still normal. The number of irregularly shaped (gourd-shaped) follicles was also increased. Excess oxidative stress was indicated by increased 8-hydroxy-2′-deoxyguanosine and 53BP1 foci in Atg5thyr-KO/KO mice. These data demonstrate that thyrocytes gradually undergo degradation/cell death in the absence of basal levels of autophagy, indicating that autophagy is critical for the quality control of thyrocytes.

The effects of propylthiouracil, thyroxine, and hypophysectomy on the iodinating activity of the rat thyroid gland

1968 ◽  
Vol 46 (3) ◽  
pp. 449-452 ◽  
Author(s):  
A. E. Zimmerman ◽  
C. C. Yip
Keyword(s):  
Drinking Water ◽  
Thyroid Gland ◽  
Thyroid Stimulating Hormone ◽  
Rapid Decrease ◽  
Daily Injection ◽  
The Third ◽  
Thyroxine Treatment ◽  
Rat Thyroid ◽  
Rat Thyroid Gland ◽  
Stimulating Hormone

The effects of increasing or decreasing the endogenous secretion of thyroid-stimulating hormone on the iodinating activity of the rat thyroid gland were investigated. The thyroid iodinating activity of rats on 0.01% propylthiouracil in the drinking water increased linearly for 3 days and reached a maximum of 230 to 240% of the control on or about the fourth day of treatment. The daily injection of thyroxine (10 μg/100 g intraperitoneally) or hypophysectomy resulted in a rapid decrease in the iodinating activity between the first and second day, approaching a basal level by the third day. When the iodinating activity was suppressed for 4 days by daily injections of thyroxine, the activity began to rise on the fifth day after termination of thyroxine treatment.

Chromatin distribution pattern and cell functioning

1986 ◽  
Vol 64 (9) ◽  
pp. 1908-1913 ◽  
Author(s):  
T. S. Sahota ◽  
F. G. Peet ◽  
A. Ibaraki ◽  
S. H. Farris
Keyword(s):  
Epithelial Cell ◽  
Distribution Patterns ◽  
Functional Differentiation ◽  
Cell Populations ◽  
Dendroctonus Pseudotsugae ◽  
Functional Changes ◽  
Pathological Conditions ◽  
Follicular Epithelial Cell ◽  
Two Populations ◽  
Follicular Epithelial

Chromatin distribution patterns of the nuclei of the follicular epithelial cell of Dendroctonus pseudotsugae Hopk. (Scolytidae: Coleoptera) were analyzed after creating their digital images. The five cell populations examined consisted of follicular epithelial cells at three different stages of structural and functional differentiation and two populations in which this differentiation was blocked. The results show that chromatin distribution patterns differ when cells are structurally and functionally different but are not different in cells that are structurally, developmentally, and functionally similar. The procedures are capable of detecting minute differences and appear useful for early detection of developmental and functional changes in relation to normal and pathological conditions.

Importance of lymph extranodal extension to therapy outcomes in patients with thyroid follicular epithelial cell-derived carcinoma evaluated at one year

2021 ◽  
Author(s):  
Hernández Olmeda Fernando ◽  
Espinosa De Los Monteros Patricia ◽  
Pérez Candel Xavier ◽  
Nevado Celia Lopez ◽  
Pallarés Raquel ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Therapy Outcomes ◽  
Extranodal Extension ◽  
Follicular Epithelial Cell ◽  
One Year ◽  
Follicular Epithelial

The Effects on Rat Thyroid Function of an Hepatic Microsomal Enzyme Inducer

1993 ◽  
Vol 12 (2) ◽  
pp. 153-158 ◽  
Author(s):  
S. Johnson ◽  
D. McKillop ◽  
J. Miller ◽  
I.K. Smith
Keyword(s):  
Hepatic Clearance ◽  
Liver Weight ◽  
Thyroid Stimulating Hormone ◽  
Albino Rats ◽  
Histopathological Changes ◽  
Hepatic Microsomal Enzyme ◽  
Pituitary Thyroid Axis ◽  
Related Enzyme ◽  
Rat Thyroid ◽  
Follicular Epithelial

1 Following daily administration to male albino rats for 2 weeks, β-naphthoflavone (25 and 60 mg kg-1, i.p.) and phenobarbitone (100 mg kg-1, p.o.) produced their characteristic patterns of induction of P450-related enzyme activities. β-naphthoflavone also induced p-nitrophenol glucuronidation by 160% over controls, while phenobarbitone produced only a 45% induction of this conjugation activity. 2 β-Naphthoflavone produced significant reductions in plasma thyroxine (T4) concentrations on days 4 and 16 and also decreased tri-iodothyronine (T3) on day 4. Thyroid-stimulating hormone (TSH) was significantly increased on day 16 by the higher dose of β-naphthoflavone. Thyroid weight was significantly increased at both dose levels on day 16 and liver weight was significantly increased on both days 4 and 16. No histopathological changes were seen in the liver or pituitary, but 30% of the animals showed minimal to mild follicular epithelial hypertrophy of the thyroid gland. 3 Phenobarbitone had no effect on T4 concentrations, but significantly decreased T3 on day 4. TSH increased by 60% on day 16, but was not statistically significant compared with controls. Thyroid weight was significantly increased on day 16 and liver weight was significantly increased on days 4 and 16. Mild to moderate thyroid follicular epithelial hypertrophy and moderate hepatocyte hypertrophy occurred in all animals. No histopathological changes were seen in the pituitary. 4 The early changes in T4 and/or T3 were probably due to increased hepatic clearance by induction of thyroxine glucuronidation with both compounds. Thyroid hypertrophy would be expected to follow as a result of activation of the hypothalamic-pituitary-thyroid axis. Data for the two compounds suggest some variation in the precise mechanism of action, which has not yet been fully elucidated.

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