Cloning and sequencing of complete thyrotropin receptor transcripts in pretibial fibroblast culture cells

Wu, Shih-Lu; Chang, T. C.; Chang, Tien‐Jye; Kuo, Yea-Fhey; Hsiao, Yung-Lien; Chang, Cheng-Chi

doi:10.1007/bf03344971

Cited by 21 publications

(15 citation statements)

References 22 publications

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“…TSHR mRNA transcripts and immunoreactivity have previously been reported in orbital (41)(42)(43) and pretibial (12,13) fibroblast-like cells in Graves' disease. In our view, the important aspect of our findings, and the basis for our present hypothesis, is that we also observed TSHR immunoreactivity in dermal fibroblasts from individuals without Graves' disease.…”

Section: Discussionmentioning

confidence: 94%

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Elephantiasic Pretibial Myxedema: Insight into and a Hypothesis Regarding the Pathogenesis of the Extrathyroidal Manifestations of Graves' Disease

Rapoport

Alsabeh

Aftergood

et al. 2000

Thyroid

110

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The basis for the extrathyroidal manifestations of Graves' ophthalmopathy (GO) and dermopathy are not well understood. We describe immunohistochemical studies on the skin of a patient with an extreme, elephantiasic form of Graves' dermopathy that developed after periods of prolonged standing with dependent edema. Excision of part of the lesion with subsequent skin grafting from a normal donor site resulted in recurrence of the disease at the original site as well as in development of disease at the donor site. A murine monoclonal antibody reacted with the thyrotropin receptor (TSHR) or a cross-reacting protein in fibroblast-like cells in the patient's upper dermis and, surprisingly, with dermal cells from unaffected individuals. The patient's dermis containing lymphoid follicles comprising B cells and CD3+, CD4+ T cells, with few CD8+ T cells. CD21+ cells (most likely follicular dendritic cells) were also present in the dermis. Based on past and present observations, we raise an unifying hypothesis to explain the diverse extrathyroidal manifestations of Graves' disease and their apparent lack of association with TSHR autoantibodies. As opposed to the present concept that these phenomena relate to site-specific properties on preadipocytes or fibroblasts, we suggest that clinically evidence GO and dermopathy are primarily caused by local factors (particularly in the orbit) superimposed on a systemic, low-grade connective tissue inflammation.

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Section: Discussionmentioning

confidence: 94%

“…TSHR mRNA transcripts have now been detected in many such tissues (reviewed in refs. 3,11), including fibroblasts cultured from Graves' dermopathy lesions (12,13). In most tissues, the extent and functionality of TSHR expression is unknown.…”

Section: Introductionmentioning

confidence: 99%

Elephantiasic Pretibial Myxedema: Insight into and a Hypothesis Regarding the Pathogenesis of the Extrathyroidal Manifestations of Graves' Disease

Rapoport

Alsabeh

Aftergood

et al. 2000

Thyroid

110

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“…It has been speculated that the thyroid-stimulating hormone receptor antibody plays a role (11,12). Heat shock protein (13), IL-1, and TGF-␤ (14) have also been implicated in PTM, although their roles are not clearly defined.…”

Section: Cause Of Thyroid Dermopathymentioning

confidence: 99%

Dermopathy of Graves’ Disease (Pretibial Myxedema): Long-Term Outcome

Schwartz¹,

Fatourechi²,

Ahmed³

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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Little is known about the long-term outcome of patients with thyroid dermopathy, an extrathyroidal manifestation of Graves' disease. Also, it is not known to what degree treatment promotes remission of the lesions. The present report supplies information on the natural course of mild, untreated and severe, treated thyroid dermopathy. In this study, we report on the outcomes of 178 patients seen at our institution between January 1969 and November 1995 with thyroid dermopathy who were followed up for an average of 7.9 yr. Nonpitting edema was the most prevalent form of dermopathy (43.3%), and the pretibial area was the region most commonly involved (99.4%). The majority of patients with dermopathy had ophthalmopathy (97.0%). Topical corticosteroids were the most commonly used treatment (53.9%). Patients with milder forms of dermopathy (40.4%) did not receive any therapy for dermopathy. Twenty-six percent of the patients experienced complete remission, 24.2% had moderate improvement (partial remission), and 50.0% had no or minimal improvement of their dermopathy at last follow-up. Patients who did not receive therapy experienced a significantly (P = 0.03) higher rate of complete remission (34.7%) than those who received local therapy (18.7%), although the combined complete and partial remission rates were not significantly different for the treated and untreated groups (P = 0.3). However, the treated and untreated groups were not comparable because our practice is to use therapy for more extensive and severe cases. All five cases of elephantiasis were in the treatment group and were less likely to have remission because of the severity of their skin condition. Patients receiving treatment were more likely to have dermatologic consultation and histologic diagnosis (P < 0.001). The beneficial effect of topical corticosteroid therapy on long-term remission rates remains to be determined.

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“…The seventh segment is followed by a hydrophilic carboxyl terminal domain that resides within the cytoplasmic compartment. To this group belong the parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor which is expressed in dermal fibroblasts but not in epidermal keratinocytes [32, 33], the thyroid-stimulating hormone (TSH) receptor which is present in dermal fibroblasts [34], the CRH receptors from which type 1 is present in epidermal and follicular keratinocytes, melanocytes, and dermal fibroblasts, whereas sebocytes express types 1 and 2 [4, 19], the melanocortin receptors (MCR), among them MCR1 which presents high affinity for α-MSH and ACTH and is expressed in epidermal and follicular keratinocytes, epidermal and follicular melanocytes, sebocytes, sweat gland cells, endothelial cells, Langerhans cells, monocytes, macrophages, lymphocytes and dermal fibroblasts, MCR2 which is specific for ACTH and is expressed in epidermal melanocytes and adipocytes, and MCR5 which shows affinity for α-MSH and ACTH and is present in sebocytes, sweat gland cells and adipocytes [4, 12, 35, 36], the µ-opiate receptors which bind with high affinity β-endorphin and are expressed in epidermal and outer root sheat keratinocytes, undifferentiated sebocytes and cells of the sweat gland secretory portion [4], the vasoactive intestinal popypeptide (VIP) receptors which are expressed in epidermal keratinocytes, sebocytes, sweat gland cells, endothelial cells, mononuclear cells and dermal nerve fibers [37, 38, 39], the neuropeptide Y receptor which is present in sebocytes [38], and the calcitonin gene-related peptide (CGRP) receptor which is expressed in sebocytes and Langerhans cells [38, 40]. …”

Section: Hormone Receptors In Human Skinmentioning

confidence: 99%

Human Skin: An Independent Peripheral Endocrine Organ

2000

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The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth factor-binding proteins. Therefore, the human skin fulfils all requirements for being the largest, independent peripheral endocrine organ.

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Cloning and sequencing of complete thyrotropin receptor transcripts in pretibial fibroblast culture cells

Cited by 21 publications

References 22 publications

Elephantiasic Pretibial Myxedema: Insight into and a Hypothesis Regarding the Pathogenesis of the Extrathyroidal Manifestations of Graves' Disease

Elephantiasic Pretibial Myxedema: Insight into and a Hypothesis Regarding the Pathogenesis of the Extrathyroidal Manifestations of Graves' Disease

Dermopathy of Graves’ Disease (Pretibial Myxedema): Long-Term Outcome

Human Skin: An Independent Peripheral Endocrine Organ

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