Thyrotrophin receptor protein expression in normal and adenomatous human pituitary

Theodoropoulou, Marily; Arzberger, Thomas; Gruebler, Yvonne; Korali, Z.; Mortini, Pietro; Joba, Werner; Heufelder, Armin E.; Stalla, GK; Schaaf, Ludwig

doi:10.1677/joe.0.1670007

Cited by 34 publications

(16 citation statements)

References 30 publications

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“…tSH, the pituitary hormone whose main role is to stimulate thyroid growth and thyroid hormone production, had no effect on GH3 cell proliferation in the t-screen, which is in agreement with previous studies (Felice et al, 2004;theodoropoulou et al, 2000). It did, nonetheless, exhibit a physiologically relevant and concentration-dependent mitogenic effect on FRtl-5 cells in the tSH-screen.…”

Section: Discussionsupporting

confidence: 91%

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

Jomaa

2013

ALTEX

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Summary This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

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Section: Discussionsupporting

confidence: 91%

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

Jomaa

2013

ALTEX

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“…More likely, thyrostimulin may play a paracrine role in the anterior pituitary and other tissues expressing TSH receptors. In addition to thyroid cells, expression of the TSH receptor has been demonstrated in the folliculo-stellate cells and thyrotrophs of human anterior pituitary based on in situ hybridization and immunohistochemistry studies (25,26). Folliculostellate cells form a network for long-distance communication in the anterior pituitary (27) but their exact role is not clear.…”

Section: Discussionmentioning

confidence: 99%

Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor

Nakabayashi¹,

Matsumi²,

Bhalla³

et al. 2002

J. Clin. Invest.

149

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IntroductionHuman thyrotropin (TSH), follitropin (FSH), lutropin (LH), and chorionic gonadotropin (CG) are members of the glycoprotein hormone family derived from heterodimerization of a common α subunit with hormone-specific β subunits. These hormones were originally purified from the anterior pituitary (TSH, LH, and FSH) and placenta (human CG) and shown to activate specific G protein-coupled receptors in the thyroid (TSH receptor) and gonads (LH and FSH receptors), respectively (1-4). These three pituitary-derived glycoprotein hormones form the basis of the classic pituitary-peripheral target feedback systems and are essential for the development and differentiation of thyroid and gonadal tissues. In particular, TSH is essential for the production of iodothyronines by the thyroid gland and disorders of the pituitary-thyroid gland-thyroid hormone axis lead to disturbances of essentially all metabolic pathways and organs (5, 6).Based on GenBank searches, we identified two additional human glycoprotein hormone subunitlike genes and named them α2 (A2) and β5 (B5), due to their structural similarities to known subunits and the chronology of discovery (7). (The GenBank accession numbers for A2 and B5 are AF403384 and AF403430, respectively.) A2 and B5 have conserved cysteine residues, similar to those found in the well-characterized α and β subunits (8, 9) important for the formation of key disulfide bonds. Like all other glycoprotein hormone subunits, A2 and B5 have the unique cystine knot structure characteristic of proteins related to the TGF-β, the PDGF, and the bone morphogenetic protein families (10, 11). Because the putative A2 subunit is likely to combine with either known or novel β subunits to yield bioactive heterodimeric hormones, we performed a yeast two-hybrid protein-protein interaction screen to identify potential dimerization partners for A2 and found interactions between A2 and B5. We generated Ab's against A2 and B5 to confirm the interactions between these putative subunits and their colocalization in the anterior pituitary. Following testing for the activation of glycoprotein hormone receptors, Human thyrotropin (TSH), luteotropin (LH), follitropin (FSH), and chorionic gonadotropin are members of the heterodimeric glycoprotein hormone family. The common α subunit forms noncovalent heterodimers with different β subunits. Two novel human glycoprotein hormonelike genes, α2 (A2) and β5 (B5), recently have been identified. Using a yeast two-hybrid assay, the two subunits were found as potential heterodimerization partners. Immunological analyses confirmed the heterodimerization of A2 and B5 in transfected cells and their colocalization in the anterior pituitary. Recombinant A2/B5 heterodimeric glycoproteins, purified using cation exchange and size fractionation chromatography, activated human TSH receptors, but not LH and FSH receptors, and showed high affinity to TSH receptors in a radioligand receptor assay. The heterodimer also stimulated cAMP production and thymidine incorporation by cultured th...

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“…TSH receptors have been identified in the anterior pituitary (Theodoropoulou, et al, 2000) offering the , possibility of a feedback loop through thyrotropin-releasing hormone. Rates of conversion have been reported in slices of human tissue, kidney, liver, heart, and skeletal muscle (Albright and Larson, 1959).…”

Section: Animal Experiments: Prevagotomy Thyrotropinmentioning

confidence: 99%

On the pulmonary toxicity of oxygen. 4. The thyroid arena

Shanklin

2012

Experimental and Molecular Pathology

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Thyrotrophin receptor protein expression in normal and adenomatous human pituitary

Cited by 34 publications

References 30 publications

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor

On the pulmonary toxicity of oxygen. 4. The thyroid arena

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