Thyrotropin Binding and Adenylate Cyclase Activation in Normal and Neoplastic Human Thyroid Tissue: Lack of Effect of Thyroglobulin

Clark, Orlo H.; Gerend, Patricia L.; Nissenson, Robert A.

doi:10.1210/jcem-54-6-1157

Cited by 15 publications

(10 citation statements)

References 21 publications

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“…Isolated HFs were either snap-frozen immediately (for RT-PCR analysis) or organ-cultured as previously described (Bodo ´et al, 2005;Ito et al, 2005a;Foitzik et al, 2006), following the basic technique pioneered by Philpott et al (1990). Bovine TSH (which activates also human TSH-R Clark et al, 1982) (1, 10, 100 mU ml À1 ) (from Sigma-Aldrich, Taufkirchen, Germany) or vehicle (distilled water) were administered once for each change of culture medium (that is every 48 h). HFs (15-20) were used per group and that all experiments where repeated twice, each experiment using HFs from one (different) individual.…”

Section: Methodsmentioning

confidence: 99%

Human Female Hair Follicles Are a Direct, Nonclassical Target for Thyroid-Stimulating Hormone

Bodó

Kromminga²,

Bı́ró

et al. 2009

Journal of Investigative Dermatology

122

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Pituitary thyroid-stimulating hormone (TSH) regulates thyroid hormone synthesis via receptors (TSH-R) expressed on thyroid epithelial cells. As the hair follicle (HF) is uniquely hormone-sensitive and, hypothyroidism with its associated, increased TSH serum levels clinically can lead to hair loss, we asked whether human HFs are a direct target for TSH. Here, we report that normal human scalp skin and microdissected human HFs express TSH-R mRNA. TSH-R-like immunoreactivity is limited to the mesenchymal skin compartments in situ. TSH may alter HF mesenchymal functions, as it upregulates alpha-smooth muscle actin expression in HF fibroblasts. TSH-R stimulation by its natural ligand in organ culture changes the expression of several genes of human scalp HFs (for example keratin K5), upregulates the transcription of classical TSH target genes and enhances cAMP production. Although the functional role of TSH in human HF biology awaits further dissection, these findings document that intracutaneous TSH-Rs are fully functional in situ and that HFs of female individuals are direct targets for nonclassical, extrathyroidal TSH bioregulation. This suggests that organ-cultured scalp HFs provide an instructive and physiologically relevant human model for exploring nonclassical functions of TSH, in and beyond the skin.

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Section: Methodsmentioning

confidence: 99%

Human Female Hair Follicles Are a Direct, Nonclassical Target for Thyroid-Stimulating Hormone

Bodó

Kromminga²,

Bı́ró

et al. 2009

Journal of Investigative Dermatology

122

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“…Classically, TSH is considered the most important trophic factor for the thyroid gland [6,7,44,45]. However, the exact role of TSH is not clear and results are controversial, because the effect of TSH on growth of follicular thyroid cells differs in different species.…”

Section: Discussionmentioning

confidence: 99%

Aberrations of growth factor control in metastatic follicular thyroid cancerin vitro

Hoelting¹,

Zielke²,

Siperstein³

et al. 1994

Clin Exp Metast

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The aggressiveness of follicular thyroid cancer (FTC) varies widely, and metastasis is the primary cause of death. Uncontrolled proliferation of cancer cells may be associated with loss of growth factor control. We investigated the effects of stimulating (epidermal growth factor [EGF]; thyreotropin [TSH] in low concentrations) and inhibiting growth factors (transforming growth factor beta 1 [TGF beta 1]; TSH in high concentrations) on invasion and growth of FTC cell lines from the thyroid tumor (FTC133) and from the lymph node (FTC236) and lung (FTC238) metastases of the same patient. Invasion-penetration through an 8 microns pore membrane, covered by Matrigel (basement membrane)-and growth were measured using the MTT-method. EGF (10 ng/ml) and TSH in low concentrations (1 mU/ml) stimulated invasion and growth of all FTC cell lines, but the amplitude of stimulation differed significantly. The parental cell line FTC133 was considerably more responsive to growth factor stimulation than the metastatic clones. Invasion of FTC133 was enhanced by 42% (EGF; p < 0.02) and 21% (TSH; p < 0.01), invasion of FTC236 by 8% (EGF; p < 0.02) and 8% (TSH; p < 0.01), and invasion of FTC238 by 9% (EGF; p < 0.02) and 8% (TSH; p < 0.01). Conversely, invasion and growth of FTC133 were significantly more inhibited by TGF beta 1 (10 ng/ml) and supraphysiologic concentrations of TSH (100 mU/ml) than the cell lines from the lymph node and lung metastases. At day 7, invasion of FTC133 was inhibited by 32% (TGF beta 1; p < 0.02) and 21% (TSH; p < 0.01), invasion of FTC236 by 18% (TGF beta 1; p < 0.02) and 11% (TSH; p < 0.01), and invasion of FTC238 by 16% (TGF beta 1; p < 0.02) and 12% (TSH; p < 0.01). Moreover, we analyzed growth factor independence in minimally supplemented or unsupplemented medium. Growth, but no invasion was evident when cells were cultured completely unsupplemented over 7 days. These results suggest that metastatic FTCs may have developed by escaping from the normal control of TSH and other growth factors.

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“…Many thyrotropin (thyroid-stimulating hormone, TSH) effects on thyrocytes are known to be transduced via adenylate cyclase. TSH stimulates growth and increases cAMP production in normal and neoplastic human thyroid tissues [7]. Thyrotropin also increases cAMP and stimulates growth of cultured human follicular thyroid cells (FTC-133) [8].…”

Section: ) ]L] Tumor Cells Of High Metastatic Potentialmentioning

confidence: 99%

Diminished expression of the α5β1 integrin (fibronectin receptor) by invasive clones of a human follicular thyroid cancer cell line

et al. 1994

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Altered adhesion plaques have been observed in transformed cell lines and are associated with enhanced metastatic potential. The prototypical adhesion plaque is formed by alpha 5 beta 1 fibronectin receptors (FnRs) interacting with the cellular actin network. We have found differences in the actin networks of noninvasive (FTC-133) and invasive (FTC-236, FTC-238) clones of a human follicular thyroid cancer cell line. Furthermore, thyroid-stimulating hormone (TSH) induces stress fibers in FTC-133. In order to investigate differences in adhesion plaques, expression of fibronectin (FN) and its receptor by these cells was analyzed. For these studies FTC-133, FTC-236, and FTC-238 were cultured in serum-depleted DME-H21 medium for 24 hours before the addition of TSH 30 mU/ml. No quantitative differences were noted in FN expression on Western blot in either the conditioned medium or cellular extracts. Western blots and immunohistochemical studies indicated that TSH induced secretion of FN only in FTC-133. Flow cytometry with an alpha 5 antibody demonstrated a 52% and 45% reduction (p < 0.01) in expression of FnR by FTC-236 and FTC-238, respectively, compared to FTC-133; this finding was supported by immunohistochemistry results. TSH treatment did not alter FnR expression. From these studies, we conclude that invasive clones of FTC decrease their expression of FnRs without changing their expression of FN. Furthermore, TSH treatment may promote FN secretion by FTC-133, although it does not seem to affect FnR or absolute FN expression. The diminished expression of FnR adhesion plaques may enhance metastatic potential in some follicular thyroid cancers.

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Thyrotropin Binding and Adenylate Cyclase Activation in Normal and Neoplastic Human Thyroid Tissue: Lack of Effect of Thyroglobulin

Cited by 15 publications

References 21 publications

Human Female Hair Follicles Are a Direct, Nonclassical Target for Thyroid-Stimulating Hormone

Human Female Hair Follicles Are a Direct, Nonclassical Target for Thyroid-Stimulating Hormone

Aberrations of growth factor control in metastatic follicular thyroid cancerin vitro

Diminished expression of the α5β1 integrin (fibronectin receptor) by invasive clones of a human follicular thyroid cancer cell line

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