Evidence of Thyrotropin-Releasing Hormone (TRH) and TRH-Binding Sites in Human Nonsecreting Pituitary Adenomas

Dafniet, M. Le; Grouselle, Dominique; Li, J. Y.; Kujas, M; Bression, D.; Barret, Alain; Tixier-Vidal, A; Peillon, F

doi:10.1210/jcem-65-5-1014

Cited by 24 publications

(19 citation statements)

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“…Highperformance liquid chromatography showed only one peak of immunoreactive material that eluted at the same position than synthetic 3H-TRH. The concentrations of immunoreactive TRH were in the same range as those obtained in nonsecreting adenomas and normal human pituitary [20].…”

Section: Trh Content O F Adenomatous Tissuesupporting

confidence: 71%

“…However, other authors have shown that SRIH receptors, although not numerous, could be present in nonsecreting adenomas. This proba bly explains the possible therapeutical effect of SRIH analogues in such cases [19], In a study focused on nonsecreting adenomas com pletely devoid of immunoreactive cells, we found spe cific TRH receptors in nearly all these adenomas [20]. The mean IQ of TRH-binding sites was similar to that found in PRL-and GH-secreting adenomas and in nor mal human pituitary.…”

Section: Receptor Studies In Nonsecreting Pituitary Adenomassupporting

confidence: 70%

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Receptors and Neurohormones in Human Pituitary Adenomas

Peillon

Dafniet²,

Garnier³

et al. 1989

Horm Res

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In order to go further into the pathogenesis of human pituitary adenomas, we studied receptors for neurohormones (thyroliberin, TRH; dopamine, DA; somatostatin, SRIH), for estradiol and epidermal growth factor (EGF) thought to influence hormone secretion and/or cell growth. The following results were obtained: (1) the receptors listed above, with the exception of EGF receptors in the adenomas, are present in normal pituitary tissue and in prolactin (PRL)- and growth hormone (GH)-secreting adenomas; (2) they are functional and their affinities are not different in normal or tumoral tissues; (3) their density is variable and depends on the type of secreting adenoma (GH or PRL), the size of the tumor and the plasma level of the hormone which is secreted, and (4) in nonsecreting adenomas, only TRH receptors are found with characteristics identical to those observed in secreting adenomas. We also showed that TRH is contained in normal and tumoral pituitary tissues. TRH and SRIH are released in vitro from adenomatous cells in large amounts, suggesting their possible synthesis by the pituitary. In both cases a local regulation is observed. TRH release is stimulated in the presence of DA while SRIH is inhibited in the presence of TRH. This neuropeptide release may be implicated in the pituitary hormone regulation through a paracrine or an autocrine mechanism. Thus, the neurohormone receptors found in pituitary adenomas should be dependent on a more complex regulation than it has been envisaged till now.

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Section: Trh Content O F Adenomatous Tissuesupporting

confidence: 71%

Section: Receptor Studies In Nonsecreting Pituitary Adenomassupporting

confidence: 70%

Receptors and Neurohormones in Human Pituitary Adenomas

Peillon

Dafniet²,

Garnier³

et al. 1989

Horm Res

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“…PAM activity is expressed in all pituitary hormone-producing cells of the AP, a finding consistent with the presence of a multitude of regulatory peptides, many of which are amidated, in the pituitary gland (16,37,38). To investigate whether TRH acts in a paracrine fashion within cultured AP cells, we chose Dis as a highly specific tool to reduce the formation of bioactive TRH, which we previously established to be expressed in this system (11,12,15,16,28).…”

Section: Discussionmentioning

confidence: 78%

Thyrotropin-Releasing Hormone Gene Expression in the Anterior Pituitary. IV. Evidence for Paracrine and Autocrine Regulation

1998

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Disulfiram (Dis), an inhibitor of peptidyl-glycine ␣-amidating monooxygenase, the enzyme responsible for the production of ␣-amidated peptides from their immediate, glycine-extended precursors was used to investigate the paracrine effects of TRH on anterior pituitary (AP) hormone secretion. It reduces the production of TRH without directly affecting the classical pituitary hormones, none of which is amidated.Dis (8 M) decreased the accumulation of TRH accompanied by an equimolar increase in TRH-Gly levels, indicating that pro-TRH biosynthesis persisted. TRH and TSH release into the medium was significantly lowered, whereas other pituitary hormones were unaffected. In contrast, dexamethasone (10 nM), which up-regulates TRH gene expression in this system, increased TRH (ϩ89.5%) and TSH (ϩ61.3%) secretion. The combination of dexamethasone and Dis further diminished the release of TRH (Ϫ73%) and TSH (Ϫ40.3%) observed with Dis alone, indicating that TRH synthesized within the AP regulates TSH secretion.Dis significantly elevated prepro-TRH (25-50) and pro-TRH messenger RNA levels, suggesting that reduced TRH formation leads to increased pro-TRH biosynthesis and that TRH regulates its own secretion. Thus, TRH synthesized by cultured AP cells not only stimulates TSH release through a paracrine effect, but has a negative feedback on its own biosynthesis by an autocrine mechanism. (Endocrinology 139: 3416 -3422, 1998)

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“…Reverse transcription was performed by incubating 1 mg total RNA with 1 ml of PowerScript reverse transcriptase (Clontech, USA) and 1 ml of 0.5 mg/ml oligo(dT) [12][13][14][15][16][17][18] primer (Life Technologies, USA) at 42°C for 70 minutes in 20 ml reaction buffer. RT products were diluted ten times with 10 mM Tricine-KOH (pH 9.2)/0.1 mM EDTA, and stored at -20°C until used for PCR.…”

Section: Histological Studiesmentioning

confidence: 99%

Gene Expression Study of Thyrotropin Releasing Hormone (TRH) Receptor Using RT-PCR: Relationship to Clinical and Immunohistochemical Phenotypes in a Series of Human Pituitary Adenomas

et al. 2003

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Abstract. Thyrotropin releasing hormone receptor 1 (TRHR1) and 2 (TRHR2) mRNAs were examined using reverse transcription polymerase chain reaction (RT-PCR). These data were then correlated with endocrinological and histological characteristics in 65 human pituitary adenomas including one non tumorous pituitary gland, to clarify the role of TRHR1 and 2 gene expression in human pituitary adenomas, especially as it relates to the paradoxical stimulatory effects of TRH found in pituitary adenomas. TRHR mRNA was not identified in four ACTH cell adenomas, whereas TRHR mRNA expression was found in 12/23 acromegaly specimens, 7/8 prolactinomas, 3/3 TSH cell adenomas, and 22/27 clinically nonfunctioning adenomas. Specimens obtained from patients expressing the TRHR gene were found to express TRHR1 and TRHR2 or TRHR1 alone, whereas no cases were identified in which TRHR2 alone was expressed. In examining the relationship between GH, PRL, TSH, or gonadotropin subunit response to TRH administration and TRHR gene expression, TRHR mRNA was found to be absent in 9 out of 10 GH cell adenomas without paradoxical GH response to TRH (non-responder), whereas TRHR genes were shown to be expressed in 10 out of 12 GH cell adenomas with paradoxical GH response to TRH (responders) (c 2 = 11.73, p = 0.0009). However, there was no significant correlation between TRHR gene expression and responsiveness to PRL or gonadotropins to TRH administration in PRL cell adenomas (c 2 = 0.16, p = 0.87) or gonadotroph cell adenomas (c 2 = 0.0006, p = 1), respectively. We concluded that the existence of the TRH receptor in adenoma cells plays an important role in the paradoxical GH response to TRH administration in GH cell adenomas. It should be noted that the PRL response to TRH in prolactinoma or an abnormal response of gonadotropin and/or its subunits to TRH in gonadotroph cell adenomas is considered to be due to a mechanism other than direct TRH action in adenoma cells. However, further studies are required to elucidate the role of TRHR2 in pituitary adenomas.

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Evidence of Thyrotropin-Releasing Hormone (TRH) and TRH-Binding Sites in Human Nonsecreting Pituitary Adenomas

Cited by 24 publications

References 0 publications

Receptors and Neurohormones in Human Pituitary Adenomas

Receptors and Neurohormones in Human Pituitary Adenomas

Thyrotropin-Releasing Hormone Gene Expression in the Anterior Pituitary. IV. Evidence for Paracrine and Autocrine Regulation

Gene Expression Study of Thyrotropin Releasing Hormone (TRH) Receptor Using RT-PCR: Relationship to Clinical and Immunohistochemical Phenotypes in a Series of Human Pituitary Adenomas

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