Spontaneous Vacuolar Degeneration of the Thyroid Follicular Epithelium in
          Cynomolgus Monkeys

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Abstract

Vacuolar degeneration of the thyroid follicular epithelium was observed in two untreated female cynomolgus monkeys assigned to control groups. In light microscopy, large vacuoles containing a homogenous substance occupied the basal region of the epithelium, and the nuclei had shifted toward the apical region. The vacuoles showed negative reactions to PAS and thyroglobulin. Electron microscopic observation revealed dilatation of the rough endoplasmic reticulum corresponding to the vacuoles. The plasma TSH, T3 and T4 levels determined for the samples kept frozen were within the normal ranges, suggesting that the thyroid function was kept intact.

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Missing secretory granules, dilated endoplasmic reticulum, and nuclear dislocation in the thyroid gland of rdw rats with hereditary dwarfism.

S Furudate, S. Yamashina, Lynn Sakai (2000)

Previous studies on the rdw rat have suggested that its dwarfism is caused primarily by dysfunction of the thyroid gland. In this study, rat thyroid glands were analyzed endocrinologically and morphologically to clarify the primary cause of dwarfism in the rdw rat. The rdw rat showed lowered thyroid hormone (T4 and T3) levels but elevated TSH in serum. The rdw thyroid gland was almost proportional in size and it was not goiter in gross inspection. Our histological investigation produced three results that may lend important evidence in understanding the problem in the thyroid gland of rdw rats. First of all, secretory granules could not be detected in the follicular epithelial cells of the rdw. Secondly, thyroglobulin was found at very low levels in the follicular lumen by immunohistochemical analysis. In contrast, it could be detected in a substantial quantity inside the dilated rER and in the huge vacuoles that are formed by swelling of the rough endoplasmic reticulum (rER) at the basal side of the follicular epithelial cells. Additionally, the nucleus of the follicular epithelial cells was pressed to the luminal side by the enlarged rER. These morphological changes would indicate that the transport of thyroglobulin is stopped at or before the formation of the secretory granules and thyroglobulin is not secreted into the follicular lumen. The rdw characterization strongly supports that rdw dwarfism is induced by hypothyroidism due to some defect(s) in the thyroid gland. Copyright 2000 Wiley-Liss, Inc.

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Evaluation and Characterization of the hyt/hyt Hypothyroid Mouse

Stuart Stein, Douglas Shanklin, Ladislav Krulich … (1989)

The hyt/hyt mouse (BALB/cBY-hyt, C.hytRF) provides a useful model for exploring the effect of inherited severe primary hypothyroidism. Studies were undertaken to try to define the basis of the primary hypothyroidism in mice homozygous for the autosomal recessive gene, hyt. These mice had congenital hypothyroidism of fetal onset after 15 days post conception. Through their lifetime, the hyt/hyt mice had reduced serum thyroxine (T 4 ), triiodothyronine (T 3 ), reduced thyroid gland intralumenal colloid on electron microscopy and a 100-fold elevation of TSH-like activity compared to hyt/+ littermates. Thyroglobulin made in hyt/hyt animals was similar in size to normal thyroglobulin which was inconsistent with a major structural thyroglobulin gene defect. The thyroglobulin was iodinated. Marked, erratic dilation of rough endoplasmic reticulum (RER) was noted in hyt/hyt mouse follicular cells. Despite these ultrastructural findings, pulse chase and immunoprecipitation studies with isolated hyt/hyt and normal thyroid glands indicated that normal thyroglobulin processing occurred in the RER and Golgi of the hyt/hyt mice. The hyt/hyt thyroid glands were hypoplastic compared to hyt/ + littermates. Histologically, the hyt/hyt thyroid glands demonstrated an increase in smaller follicular cells, and greater variability in follicular size compared to hyt/ + littermates. Histological and ultrastructural abnormalities in the gland were similar to those seen in certain cases of human congenital hypothyroidism with TSH receptor insensitivity of the thyroid gland. These findings along with the significant TSH elevation, the reduction in colloid and in serum T 3 and T 4 , the efficacy of the hypothalamo-pituitary-thyroid feedback system, and previous observations of reduced iodine uptake and intrathyroidal T4 [3], suggested that primary hypothyroidism in the hyt/hyt mouse might be due to a defect in TSH responsivity of the thyroid gland.

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Ultrastructural aspects of the goiter in cog/cog mice.

A Mayerhofer, A G Amador, W Beamer … (2015)

Thyroids of congenitally goitrous (cog/cog) mice were studied with light and electron microscopy. The principal alteration in follicular cells was their largely overdistended rough endoplasmic reticulum (RER). Our findings resemble the ultrastructural features of human hypothyroid goiter caused by a thyroglobulin (TG) defect and thus support the previously suggested abnormalities of TG synthesis and/or processing in cog/cog mice.

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Journal

Journal ID (nlm-ta): J Toxicol Pathol

Journal ID (publisher-id): TOX

Title: Journal of Toxicologic Pathology

Publisher: The Japanese Society of Toxicologic Pathology

ISSN (Print): 0914-9198

ISSN (Electronic): 1881-915X

Publication date (Print): December 2011

Publication date (Electronic): 07 January 2012

Volume: 24

Issue: 4

Pages: 229-232

Affiliations

[1 ]Pathology Department, Safety Research Center, Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan

Author notes

Mailing address: Hirofumi Hatakeyama, D.V.M, DJST. Pathology Department, Safety Research Center, Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan TEL: 81-265-72-6616 FAX: 81-265-72-6657 E-mail: h-hata@ 123456ina-research.co.jp

Article

Publisher ID: 0600

DOI: 10.1293/tox.24.229

PMC ID: 3266358

PubMed ID: 22319235

SO-VID: b4a861c7-111d-46dc-9807-d30e2853c299

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This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

Spontaneous Vacuolar Degeneration of the Thyroid Follicular Epithelium in Cynomolgus Monkeys

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Most cited references 5

Missing secretory granules, dilated endoplasmic reticulum, and nuclear dislocation in the thyroid gland of rdw rats with hereditary dwarfism.

Evaluation and Characterization of the hyt/hyt Hypothyroid Mouse

Ultrastructural aspects of the goiter in cog/cog mice.

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