The IGF‐I receptor sub‐membrane domain is intact in GH‐secreting pituitary tumours

Greenman, Yona; Prager, Dlane; Melmed, Shlomo

doi:10.1111/j.1365-2265.1995.tb01858.x

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…However, no mutations in the gene for the GH-receptor were observed in our series of sporadic pituitary tumors [20], although others have claimed mutations in a subset of sparsely-granulated somatotroph tumors [21]. Earlier research by Melmed et al showed that mutations of the IGF-1 receptor were also not commonly seen [22].…”

Section: Abnormalities In Signalling Pathwayscontrasting

confidence: 50%

The molecular biology of pituitary tumors: a personal perspective

Grossman

2008

Pituitary

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Oncogenes and tumor suppressor genes involved in most common cancers are not involved in the great majority of pituitary adenomas. Similarly, there is little evidence to suggest that the mutations involved in genetic syndromes associated with pituitary tumors (such as the gsp, MEN1, PKAR1A or AIP mutations) are common in sporadic tumors. A novel pituitary tumor transforming gene (PTTG, securin) has been identified which is over-expressed in most tumors--but it is unclear as to its causal role in oncogenesis. Cell signaling abnormalities have been identified in pituitary tumors but their genetic basis is unknown. However, both the Akt pathway and the MAPK pathway are over-expressed in many pituitary tumors, which results in the inhibition of cell cycle inhibitors. These pathways share a common root in the tyrosine kinase receptor, and a change to these receptors or their relationship to membrane matrix-related proteins may be an early event in tumorigenesis.

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Section: Abnormalities In Signalling Pathwayscontrasting

confidence: 50%

The molecular biology of pituitary tumors: a personal perspective

Grossman

2008

Pituitary

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“…We also sequenced the coding region of the GH receptor gene in 15 somatotroph adenomas, but apart from known polymorphisms no other alteration of the sequence was identified [37]. No mutations had previously been found in the IGF receptor β-subunit in 19 somatotroph adenomas [38]. …”

Section: Feedback Regulation In Adenomasmentioning

confidence: 99%

Akting and Cycling: A Tale of the Pituitary

Grossman¹,

Korbonits²

2004

Horm Res Paediatr

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Pituitary tumours are characterized by a series of phenotypic abnormalities, but the molecular nature of the underlying defects has proved peculiarly intractable. Oncogenes and tumour suppressor genes involved in other tumours do not appear to play a major role in the pathogenesis of pituitary tumours. In addition, germline genetic disorders in which pituitary tumours are a common feature have not shed much light on the more common sporadic tumour. A number of defects in specific feedback regulation in the secretory tumours have been identified, but it is presently unclear as to what extent these are a consequence of the tumour, possibly enhancing its growth or survival, rather than the cause. However, recent studies on the cell cycle have demonstrated significant abnormalities that have been traced to a cytoplasmic kinase which appears to be abnormally expressed in the majority of pituitary adenomas, and we are beginning to see a possible unifying abnormality.

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“…Alternatively, receptor mutations or postreceptor abnormalities might be present. However, analysis of a submembrane domain in the IGF-I receptor that is important for ligand-mediated signaling did not find any mutations in 19 GH-secreting tumors (26). More studies are needed to define the pathophysiology behind the attenuated IGF-I feedback in acromegaly.…”

Section: Discussionmentioning

confidence: 97%

Regulation of GH Secretion in Acromegaly: Reproducibility of Daily GH Profiles and Attenuated Negative Feedback by IGF-I

Jaffe

Pan

Brown

et al. 2001

The Journal of Clinical Endocrinology &Amp; Metabolism

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GH hypersecretion is a hallmark of acromegaly. It is unknown whether the secretory activity of somatotroph adenoma is autonomous or is still governed by central or peripheral mechanisms. In this study we investigated whether GH secretion in acromegaly 1) has a reproducible circadian pattern and 2) is inhibited by exogenous IGF-I. Eleven patients with newly diagnosed acromegaly were studied in 2 protocols. In protocol 1, peripheral blood was sampled every 10 min for 48 h in 6 patients for the determination of concordance between 24-h GH profiles. There was no significant day to day variability in mean 24-h output. There was, however, a significant time effect, and the 24-h GH secretion pattern was maintained between days. In protocol 2, 5 patients were sampled for GH every 10 min twice, once during infusion of normal saline and once during iv infusion of recombinant human IGF-I (10 microg/kg x h). The recombinant human IGF-I infusion increased plasma IGF-I to approximately 230% of the baseline concentration. This resulted in GH suppression (4220 +/- 1950 vs. 3223 +/- 1472 microg/liter.min; P = 0.001), but did not alter GH secretion pattern. There were highly significant cross-correlations for 10 of the 11 of the subjects in the two protocols when the lag was 0 min. By harmonic analysis, nocturnal augmentation of GH was maintained, and maximum daily GH occurred at approximately 2300 h. These data demonstrate that the pattern of GH secretion in acromegaly is not random, but is highly preserved with 24-h periodicity. In addition, negative feedback regulation by IGF-I is preserved, although the degree of negative feedback is grossly attenuated. Thus, secretory activity of somatotroph adenomas is not autonomous or haphazard, but is still subject to both feedback and feedforward regulatory mechanisms.

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The IGF‐I receptor sub‐membrane domain is intact in GH‐secreting pituitary tumours

Abstract: We conclude that mutations in the IGF-I receptor sub-membrane domain which disrupt the negative feedback loop are not involved in the pathogenesis of acromegaly.

Cited by 12 publications

References 26 publications

The molecular biology of pituitary tumors: a personal perspective

The molecular biology of pituitary tumors: a personal perspective

Akting and Cycling: A Tale of the Pituitary

Regulation of GH Secretion in Acromegaly: Reproducibility of Daily GH Profiles and Attenuated Negative Feedback by IGF-I

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