Pituitary Adenomas of Patients with Acromegaly Express Thyrotropin-Releasing Hormone Receptor Messenger RNA: Cloning and Functional Expression of the Human Thyrotropin-Releasing Hormone Receptor Gene

Yamada, Masanobu; Monden, Tsuyoshi; Satoh, Tetsurou; Satoh, Noriko; Murakami, Masami; Iriuchijima, Tokuji; Kakegawa, Tadao; Mori, Masataka

doi:10.1006/bbrc.1993.2107

Cited by 60 publications

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“…The mechanism of action of TRH has been investigated in human GH-secreting adenomas in several in vitro studies (26,32). The human TRH receptor, whose gene has been cloned, is a member of the G protein-coupled receptor family (33). Mutations in this receptor might be involved in the etiology of pituitary adenomas, although a recent study found that the TRH-receptor structure was normal in TSH-, PRL-and GH-secreting pituitary adenomas (34).…”

Section: Discussionmentioning

confidence: 99%

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Iglesias²,

Sastre³

et al. 2000

European Journal of Endocrinology

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Objective: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. Methods: We studied 16 patients (8 females, aged 29±68 years) with active acromegaly and 12 control subjects (7 females, 24±65 years). All participants were tested with TRH (400 mg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between À30 and 120 min for GH and PRL determinations, and between À30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. Results: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any signi®cant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a signi®cant (P < 0.05) increase in PRL concentrations at 15±120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were signi®cantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were signi®cantly lower in patients than in controls. Infusion with rhEPO modi®ed neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. Conclusion: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modi®ed by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

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Section: Discussionmentioning

confidence: 99%

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Iglesias²,

Sastre³

et al. 2000

European Journal of Endocrinology

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“…Endogenous TRH was shown to be present in normal and adenoma pituitary cells both at the peptide and mRNA level [10][11][12]. The TRH receptor is expressed not only by thyrotroph but also somatotroph cells in normal pituitary and various pituitary adenomas including GH adenomas [13,14].…”

Section: Introductionmentioning

confidence: 99%

Somatotroph to thyrotroph cell transdifferentiation during experimental hypothyroidism ‐ a light and electron‐microscopy study

Radian

Coculescu

Morris

2003

J Cellular Molecular Medi

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Somatotroph and thyrotroph pituitary cells share a common precursor cell expressing the transcription factor Pit1 in ontogeny. Cells expressing both thyrotropin (TSH) and growth-hormone (GH) are found in adult rat pituitary and in human pituitary adenomas in acromegaly, and these tumors contain both thyrotropin-releasing hormone (TRH) and the TRH receptors (TRHR). It has been shown that stimulation of TSH expression in primary hypothyroidism promotes changes suggestive of somatotroph to thyrotroph cell transdifferentiation. We tested this hypothesis and the role of TRH in experimental primary hypothyroidism in rats. Adult female Long-Evans rats, 6 months old, were administered the antithyroid drug methimazole (0,1% w/v) in the drinking water for 42 days. Animals were sacrificed by perfusion fixation under anaesthesia at weekly intervals and pituitary tissue processed in acrylic resin for immunofluorescence and immuno-electronmicroscopy for TSH, GH and TRHR. In the hypothyroid rat pituitary immunofluorescent somatotrophs were greatly reduced in number and gradually replaced by thyrotrophs during methimazole administration. Colocalization of GH and TSH in the same cell was noted. Immunoelectronmicroscopy demonstrated the development of enlarged thyrotrophs with dilated rough endoplasmic reticulum containing an electron-dense material and intracisternal granules, both of which are immunoreactive for TSH ('thyroidectomy cells'). The somatotrophs showed reduced GH immunoreactivity and also the presence of TSH-type, small-size secretory granules. This suggests that the greatly increased number of TSH-cells in methimazole-induced-hypothyroidism is due, at least partially, to the transdifferentiation of somatotroph into thyrotroph cells. TRHR immunofluorescence was expressed in many somatotrophs in normal rat pituitary and unlike immunoreactive GH, its expression was enhanced during hypothyroidism. The number of TRHR-immunoreactive cells increased in parallel with the number of TSH-immunoreactive cells. This indicates a role for TRH stimulation in the transdifferentiation process. Taken together, these data suggest that, in addition to the cell mutation mechanism involving an early totipotential progenitor cell, transdifferentiation of existing somatotroph cells also plays a part in the pathogenesis of multihormonal GH-secreting adenomas.

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“…The isolated clones were sequenced and showed a high degree of identity to the nucleotide sequence of the region extending from the initiation codon to the fifth TMD of mouse [13], human [1,2,7,15] and rat [8][9][10][11]16] TRHR cDNAs. The N-terminus region encodes 263 amino acids.…”

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confidence: 99%

“…Reverse transcription of RNA to cDNA was carried out with Moloney Murine Leukemia Virus Reverse Transcriptase (MuLV-RT, Gibco-BRL, U.S.A.) and Oligo (dT) [12][13][14][15][16][17][18] . PCR primers were based on seven transmembrane domains (TMD) II, III and VI sequences of mouse TRHR cDNA [13].…”

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confidence: 99%

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Molecular Cloning of Bovine Thyrotropin-Releasing Hormone Receptor Gene.

Takata

Shimada

Ikeda³

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. The genomic DNA encoding bovine Thyrotropin-Releasing Hormone Receptor (TRHR) was isolated from a bovine (Holstein) genomic library. Using PCR fragments of bovine candidate TRHR Transmembrane domain (TMD-III-IV) and C-terminus domain of mouse TRHR cDNA as probes, 9 × 10 5 plaques were screened to obtain several clones each containing the N-terminus or C-terminus domain. The bovine TRHR gene encoded 398 amino acids and has a long intron. The identity of the deduced amino acid sequence of bovine TRHR exceeded 88% that of mouse, rat or human. RT-PCR analysis indicated TRHR mRNA to be expressed in the pituitary and brain. -KEY WORDS: bovine, molecular cloning, Thyrotropin-Releasing Hormone Receptor.

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Pituitary Adenomas of Patients with Acromegaly Express Thyrotropin-Releasing Hormone Receptor Messenger RNA: Cloning and Functional Expression of the Human Thyrotropin-Releasing Hormone Receptor Gene

Cited by 60 publications

References 0 publications

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Somatotroph to thyrotroph cell transdifferentiation during experimental hypothyroidism ‐ a light and electron‐microscopy study

Molecular Cloning of Bovine Thyrotropin-Releasing Hormone Receptor Gene.

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