Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As an initial step in determining whether activin could play a role in the development of gonadotroph adenomas, we attempted to determine if activin/inhibin subunit messenger ribonucleic acids (mRNAs) are expressed by these pituitary tumors. We selected 19 pituitary adenomas that had been excised by transsphenoidal surgery and determined by immunocytochemical criteria to be gonadotroph adenomas. Total RNA was extracted from these adenomas and reverse transcribed. The resulting pit-1 complementary DNA, expected to be present only in somatotroph, lactotroph, and thyrotroph cells, was amplified by the polymerase chain reaction to test the possibility that the adenoma tissue was contaminated by normal pituitary tissue. Only the 10 adenomas that did not express pit-1 mRNA were subjected to further analysis by polymerase chain reaction amplification of the adenoma reverse transcriptase products for the activin/inhibin beta B-, beta A-. and alpha-subunits. All 10 adenomas expressed beta B-subunit, none of the 10 expressed the beta A-subunit, and 6 of the 10 expressed the alpha-subunit. We conclude that gonadotroph adenomas express mRNAs for activin/inhibin beta B- and alpha-subunits. The relationship of beta B expression to the pathogenesis of gonadotroph adenomas remains to be determined.
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PMID:Expression of activin/inhibin subunit messenger ribonucleic acids by gonadotroph adenomas. 796 35

Activin A is a homodimer of inhibin beta A subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The beta A subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0.01-10 nmol recombinant human activin A/l followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12-63% above control values during treatment with 0.01-10 nmol activin A/l, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0.01-1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of recombinant human activin A on growth hormone secretion by human somatotrophinomas in vitro. 832 58

What growth factors are involved in the pathogenesis of gonadotroph adenomas is not yet known. Activin is one possible candidate because it stimulates growth and differentiation in many cells, including the gonadotroph cell, and it stimulates FSH secretion, characteristic of gonadotroph adenomas. As activin beta B-subunit is expressed in gonadotroph adenomas, we sought to determine whether activin receptor II and follistatin are also expressed. Total ribonucleic acid (RNA) was extracted from 10 gonadotroph adenomas that did not express pit-1 and was reverse transcribed. The resulting complementary DNAs for human activin receptor II and follistatin were amplified by PCR. All 10 adenomas expressed activin receptor II messenger RNA (mRNA), as did nonadenomatous pituitary tissue. Only 2 of the 10 gonadotroph adenomas expressed detectable follistatin mRNA, although all 4 nonadenomatous pituitaries did. Quantitation of follistatin mRNA by competitive reverse transcription-PCR showed that none of the 10 gonadotroph adenomas expressed as much follistatin mRNA as did the 4 nonadenomatous pituitaries, and 8 of the 10 expressed less than 10% as much. Immunospecific staining showed follistatin in the cytoplasm of the gonadotroph cells of all 5 nonadenomatous pituitaries studied, but only faintly in 1 gonadotroph adenoma and not at all in the other 9. These results suggest that pit-1-negative gonadotroph adenomas express less follistatin mRNA and follistatin peptide than do nonadenomatous gonadotroph cells. A consequence could be less binding, and thereby enhanced effectiveness, of activin, contributing to adenoma growth.
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PMID:Decreased follistatin gene expression in gonadotroph adenomas. 878 3

Inhibin alpha and beta A subunit messenger ribonucleic acid (mRNA) levels were measured quantitatively by reverse transcription-polymerase chain reaction (RT-PCR) in human pituitary adenomas. The inhibin alpha subunit mRNA levels were undetectably low in cultured adenoma tissues, but beta A mRNA were 0.383 +/- 0.074 in 3 GH adenomas, 0.672 +/- 0.140 in 3 prolactinomas and 0.957 +/- 0.414 molecules/cell in 3 non-functioning adenomas. The addition of 10(-8) M activin A decreased the beta A mRNA levels within 4 h in 1 of 3 GH adenomas, 2 of 3 prolactinomas and 2 of 3 non-functioning adenomas, though the decreases were not statistically significant. The results showed an abundance of beta A subunit mRNA compared with alpha subunit mRNA in all human pituitary adenomas and a local role for activin in its own production through inhibin beta A mRNA subunit expression.
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PMID:Inhibin alpha and beta A subunit messenger ribonucleic acids expression in human pituitary adenomas: studies by quantitative reverse transcription-polymerase chain reaction. 888 32

Inhibins and activins have been known to modify the secretion of various pituitary hormones. To study whether inhibins and activins are present in human pituitary tissues, immunohistochemical studies with antisera to activin A and inhibin alpha subunit were performed on 9 human pituitary adenoma tissue specimens and one sample of normal pituitary tissue adjacent to one adenoma. Activin immunoreactivities were demonstrated in the cytoplasms of one GH and one PRL and two non-functioning adenomas and one normal pituitary tissue, but they were negative in one PRL, one ACTH, one FSH and two non-functioning adenomas. Thus, the presence and absence of activin in the same type of adenoma in regard to hormone production, suggested that the difference in immunostaining simply reflected the difference in the activin concentration. In contrast to this, inhibin alpha subunit immunoreactivity was not found in any of the tissues studied. These data suggested a local synthesis of activin in the normal pituitary as well as various kinds of pituitary adenoma tissues and its local role in the human pituitary gland.
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PMID:Demonstration of activin in normal pituitary and in various human pituitary adenomas by immunohistochemistry. 893 May 32

Activin A belongs to the transforming growth factor-beta superfamily that exerts a wide range of biologic activities on cellular proliferation and differentiation. Although it was suggested that gonadal tissue is the primary site of activin production, several extragonadal sources have subsequently been identified, including human thyrocytes. The goal of the present study was to evaluate serum activin A levels in a series of patients with different thyroid disorders during the active state of the diseases and after recovery. Serum activin A levels were evaluated in 60 healthy subjects (controls), 8 with multinodular nontoxic goiter (MNG), 30 hyperthyroid (15 with Graves' disease (GD), 12 with autonomous hyperfunctioning adenoma (ATA), and 3 with thyrotropin (TSH)-secreting pituitary adenoma, 16 hypothyroid (11 with Hashimoto's thyroiditis and 5 after total thyroidectomy), and 9 patients with resistance to thyroid hormone (RTH) by commercial enzyme-linked immunosorbent assay (ELISA) kit. Patients with GD and ATA showed activin A levels higher than those found in controls and similar to those observed in MNG (GD, 0.74 +/- 0.3 ng/mL; ATA, 0.86 +/- 0.4; and MNG; 1.0 +/- 0.2 vs. controls: 0.39 +/- 0.5, p < 0.001), while in patients with Hashimoto's thyroiditis, total thyroidectomy or RTH activin A levels were similar to those of controls. In conclusion, this study demonstrates that thyroid hyperplasia and hyperfunction result in increased levels of activin A, although the normal levels observed in thyroidectomized patients clearly demonstrate that the thyroid gland is not the predominant source of activin A in normal conditions. Because activin A may exert negative action on thyrocyte proliferation, it is conceivable that activin A hypersecretion in thyroid disorders might represent a counteracting mechanism.
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PMID:Serum activin A levels in different thyroid disorders. 1259 25

Activins are dimeric proteins of the transforming growth factor beta superfamily, which exhibit multiple functions in gonadal and extragonadal tissues. Expression of activin A, composed of two betaA subunits, has been shown in the thyroid, whereas there has been no study regarding activin B (betaBbetaB) in this gland. In other tissues, such as the gonads, pancreas, and adrenal cortex, expression of both activin betaA and activin betaB has been described. In this study, we detected activin betaB mRNA and protein expression using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in rat experimental goiter and in human thyroid, including multinodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma. Activin betaA mRNA and protein expression was also investigated in rat and human thyroid tissue. The expression of both activin betaB and activin betaA was highest in rat methimazole-induced goiter and in human follicular adenoma, and papillary and follicular carcinomas when compared with multinodular goiter and normal thyroid tissue. The increased expression of activin betaB as well as activin betaA, observed in this study, suggests that activin B and activin A may be involved in the proliferative and neoplastic processes of the thyroid.
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PMID:Activin betaB expression in rat experimental goiter and human thyroid tumors. 1272 72

Roles of activin/bone morphogenetic protein (BMP) system in the pathogenesis of human pituitary adenoma remain unknown although these factors stimulate follicle-stimulating hormone (FSH) secretion in the normal pituitary. Here we demonstrated that type-I and -II subunit mRNAs of activin/BMP receptors are expressed in Pit-1-negative FSH-producing (FSH-oma) and nonfunctioning pituitary adenomas (NF-oma). Basal levels of serum FSH standardized by luteinizing hormone (LH) were markedly high in FSH-omas in contrast to NF-omas. However, gonadotropin-releasing hormone (GnRH)-induced increment of FSH standardized by that of LH was not changed in FSH-omas, suggesting that imbalanced FSH secretion by FSH-oma is not attributable to GnRH regardless of the expression of GnRH receptor. Although activin betaA subunit was detected in neither adenoma, the betaB subunit was expressed highly in FSH-omas and, to lesser extent, in NF-omas. As for BMPs, BMP-6 and -7 were detected in NF-omas while BMP-4 and -15 were not detected in either type of adenoma. In the presence of pituitary activin/BMP system, the levels of co-expressing follistatin mRNA in the tumors were reduced in FSH-oma compared with NF-oma, suggesting that endogenous follistatin is involved in FSH overproduction through inhibition of activin/BMP system independently of GnRH.
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PMID:Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas. 1282 Nov 14

The molecular basis of pituitary tumorigenesis remains controversial, but there are two major theories which have been subject to most investigation: hormonal (usually hypothalamic factors) and/or growth factor overstimulation, or a molecular defect within the pituitary itself. It has been shown, for example, that excessive regulatory hormone stimulation can lead to an increased number of cells in the pituitary in various physiological or pathological states such as pregnancy (lactotrophs), untreated primary hypothyroidism (thyrotrophs and lactotrophs),primary hypoadrenalism (corticotrophs) and ectopic GHRH-secreting tumours (somatotrophs). Animal models also provide data that in the presence of excessive hypothalamic hormone stimulation, adenoma formation can occur. However, evidence in favour of the monoclonal nature of pituitary tumours argues for an intrinsic molecular defect as the primary initiating event in tumour formation. We review the various hormonal factors and their receptors effecting the different types of pituitary cells, such as CRH, AVP and cortisol feedback on corticotrophs; GHRH, Galpha PKA, somatostatin and GH and IGF feedback on somatotrophs; GnRH, LH/FSH, activin and oestrogen feedback on gonadotrophs; dopamine, oestrogen and prolactin feedback on lactotrophs; and TRH, TSH and thyroid hormone feedback on thyrotrophs. The monoclonal origin of adenomas makes it unlikely that hypothalamic factors could initiate pituitary transformation, but they could still create an environment where there is a higher chance that a possible causative tumorigenic mutation may occur in one (or several) of the overstimulated pituitary cells, or enhance the proliferation of an already-mutated cell.
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PMID:Role of regulatory factors in pituitary tumour formation. 1528 40

TMEFF2 is a transmembrane protein with unknown function, containing an altered epidermal growth factor (EGF)-like motif, two follistatin-like domains, and a cytosolic tail with a putative G-protein-activating motif. TMEFF2 is predominantly expressed in brain and prostate and has been implicated in cell signaling, neuronal cell survival, and tumor suppression. We found that expression of TMEFF2 in pituitary corticotrope cells inhibits the effects of corticotropin-releasing hormone (CRH) on the production of intracellular cAMP, and CREB, and transcription of Pomc. Regulation of the activity of CRH by TMEFF2 requires neither the cytoplasmic tail nor the EGF domain, while deletion of the follistatin modules abolishes the inhibitory function of TMEFF2. Moreover, a soluble secreted protein containing the complete extracellular domain is sufficient for inhibition of CRH signaling. TMEFF2-induced inhibition depends on serum components. Furthermore, TMEFF2 regulates the non-canonical activin/BMP4 signaling, PI3K, and Ras/ERK1/2 pathways. Thus, TMEFF2 inhibits the CRH signaling pathway and the PI3K/AKT and Ras/ERK1/2 pathways, contributing to a significant inhibition of transcription of Pomc. We found that expression of TMEFF2 in human Cushing's adenoma is reduced when compared with normal human pituitary, which may indicate that TMEFF2 acts as a tumor suppressor in these adenomas. Furthermore, the overexpression of TMEFF2 decreased proliferation of corticotrope cells. Our results indicate a potential therapeutic use of TMEFF2 or factors that stimulate the activity of TMEFF2 for the treatment of corticotrope tumors in order to reduce their secretion of ACTH and proliferation.
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PMID:TMEFF2 is an endogenous inhibitor of the CRH signal transduction pathway. 2557 2


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