Disease relevance of Growth Hormone-Secreting Pituitary Adenoma

• In contrast to somatotroph adenoma seen in patients with classical acromegaly, the hypophysial lesion represents somatotroph hyperplasia in acromegalic patients with GRH-producing tumor [1].
• The highest degrees of EGF-R mRNA expression were present in somatotroph adenomas and the aggressive silent subtype 3 adenomas [2].
• Although ras mutations were not found in glycoprotein hormone-secreting or somatotroph adenomas, we recently identified a mutation in the H-ras gene (Gly-Val) at codon 12 in a highly invasive prolactinoma [3].
• Hypersecretion of the pituitary glycoprotein hormone alpha-subunit has been reported in pituitary adenomas, particularly in clinically nonfunctioning tumors and somatotroph adenomas [4].
• Phorbol ester and phospholipase C-induced growth hormone secretion from pituitary somatotroph adenoma cells in culture: effects of somatostatin, bromocriptine, and pertussis toxin [5].

High impact information on Growth Hormone-Secreting Pituitary Adenoma

• Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas [6].
• These data indicate that overexpression of GHRH gene is an event associated with the neoplastic progression and clinical aggressiveness of somatotroph adenomas [7].
• The cyclic adenosine 3',5'-monophosphate-responsive factor CREB is constitutively activated in human somatotroph adenomas [8].
• Reversible shrinkage of a growth hormone-secreting pituitary adenoma by a long-acting somatostatin analogue, octreotide [9].
• The higher number of responders of GH-secreting pituitary adenoma cultures to SOM230, compared with OCT, suggest that SOM230 has the potency to increase the number of acromegalic patients which can be biochemically controlled [10].

Chemical compound and disease context of Growth Hormone-Secreting Pituitary Adenoma

• Glycoprotein hormone alpha-subunit production in somatotroph adenomas with and without Gs alpha mutations [11].
• This article reports the effect of dopamine (DA) on adenylyl cyclase (AC) activity and intracellular free calcium concentration ([Ca2+]i) in 20 GH-secreting pituitary adenomas exclusively composed of somatotrophs (GH-omas) and 3 tumors largely constituted by mammosomatotrophs (MS-omas) [12].
• Mutant, guanosine triphosphatase-deficient, alpha-subunits of the G protein, Gs, gsp ocogene have been discovered in 40% of GH-secreting pituitary adenomas [13].
• Recent studies in molecular pathogenesis aiming to find novel therapy targets and reports on new pharmacological drugs effecting GH-secreting pituitary adenomas are reviewed (for example, lanreotide 60, SOM320 and pegvisomant) [14].
• GnRH (100 nM) increased inositol phospholipid turnover in five of five somatotroph adenomas tested by an average of 36.4 +/- 9.4% (mean +/- SE) [15].

Biological context of Growth Hormone-Secreting Pituitary Adenoma

• Impact of gsp oncogene on the expression of genes coding for Gsalpha, Pit-1, Gi2alpha, and somatostatin receptor 2 in human somatotroph adenomas: involvement in octreotide sensitivity [16].
• DESIGN: Thirteen GH-secreting pituitary adenoma postsurgical specimens were analysed for somatostatin receptor (SSTR) mRNA expression and a subset of them was analysed in vitro for the effect of somatostatin on cell proliferation, assessed by means of [3H]-thymidine uptake, and GH release, using an immunoradiometric assay [17].

Anatomical context of Growth Hormone-Secreting Pituitary Adenoma

• The effects of vasoactive intestinal polypeptide (VIP), TRH, dopamine, and rat median eminence extract on GH release from GH-secreting pituitary adenomas were studied in vitro using a sensitive superfusion method [18].
• GHRH synthesis in the pituitary gland has recently been demonstrated, however, there have been no previous reports of a GHRH-producing pituitary somatotroph adenoma associated with an elevated plasma GHRH concentration [19].
• In order to study the mechanism of GH secretion from somatotroph adenoma cells, we have compared the effect of 12-O-tetradecanoyl phorbol-13-acetate (TPA) with that of growth hormone releasing factor (GRF) on GH secretion from human somatotroph adenoma cells cultured in monolayer [20].

Gene context of Growth Hormone-Secreting Pituitary Adenoma

• GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner [21].
• Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture [21].
• Treatment with somatostatin analogues in humans causes a reduction in size and secretory activity of endocrine tumours, including GH-secreting pituitary adenomas [17].
• SSTR3 and SSTR4 mRNAs were detected in 1 and 2 cases of somatotroph adenoma, respectively [22].
• Six of 9 somatotroph adenomas, 1 of 4 lactotroph adenomas and 1 of 2 thyrotroph adenomas also expressed SSTR5 [22].

Analytical, diagnostic and therapeutic context of Growth Hormone-Secreting Pituitary Adenoma

• Interleukin-1 beta enhances interleukin-1 receptor antagonist content in human somatotroph adenoma cell cultures [23].
• Eleven patients with PRL and three with GH-secreting pituitary adenomas were treated with a single intramuscular injection of 50 mg of bromocriptine retard (Parlodel, LA (long-acting)) [24].
• We thus performed gel filtration analyses of his plasma and somatotroph adenoma to determine elution patterns of immunoreactive (IR) and receptor active (RA) GH [25].
• External beam pituitary irradiation has been frequently used in the treatment of growth hormone (GH) secreting pituitary adenomas [26].
• These data suggested that some somatotroph adenoma cells have an aberrant response to GIP which may go toward explaining paradoxical GH secretions to OGTT in acromegalics [27].

References