[show abstract][hide abstract] ABSTRACT: Regulation of cellular responses to external stimuli such as hormones, neurotransmitters, or cytokines is achieved through the control of all steps of the complex cascade starting with synthesis, going through maturation steps, release, distribution, degradation and/or uptake of the signalling molecule interacting with the target protein. One possible way of regulation, referred to as scavenging or neutralization of the ligand, has been increasingly studied, especially for small protein ligands. It shows innovative potential in chemical biology approaches as well as in disease treatment. Neutralization of protein ligands, as for example cytokines or chemokines can lead to the validation of signalling pathways under physiological or pathophysiological conditions, and in certain cases, to the development of therapeutic molecules now used in autoimmune diseases, chronic inflammation and cancer treatment. This review explores the field of ligand neutralization and tries to determine to what extent small chemical molecules could substitute for neutralizing antibodies in therapeutic approaches.
[show abstract][hide abstract] ABSTRACT: Acromegaly is a chronic disease with signs and symptoms due to growth hormone (GH) excess. The most frequent cause of acromegaly is a GH-producing pituitary adenoma. Chronic GH excess is accompanied by long-term complications of the locomotor (arthrosis) and cardiovascular (atherosclerosis, cardiomyopathy) systems and is, when untreated, associated with an increased mortality. The aim of treatment of acromegaly is to improve symptoms, to achieve local tumour mass control, and to decrease morbidity and mortality. Treatment options include surgery, medical therapy and radiotherapy. Transsphenoidal surgery is the first choice of treatment when a definitive cure can be achieved, particularly in the case of microadenomas and when decompression of surrounding structures (optic chiasm, ophthalmic motor nerves) is indicated. Primary medical therapy has been increasingly applied in recent years, especially when a priori chances of surgical cure are low (because of adenoma size and localization) and in patients with advanced age and/or serious co-morbidity. In addition, preoperative primary medical therapy may result in tumour shrinkage, facilitating tumour resection, and may reduce perioperative complications due to GH excess. Within the spectrum of medical therapy, long-acting somatostatin analogues (somatostatins) are considered as first-line treatment. Treatment with somatostatin analogues results in GH control in approximately 60% of patients. In addition, somatostatin analogues induce tumour shrinkage in 30-50% of patients, particularly when applied as primary therapy. Prolonged treatment with somatostatin analogues appears to be safe and is usually well tolerated. The currently available somatostatin analogues, octreotide and lanreotide, seem to be equally effective; however, this should still be evaluated in prospective, randomized trials evaluating efficacy with respect to GH control and tumour shrinkage. In patients with an insufficient clinical and biochemical response to somatostatin analogues, combination therapy with dopamine receptor agonists or the GH receptor antagonist pegvisomant usually leads to disease control. New developments in the medical therapy of acromegaly include the universal somatostatin receptor agonist pasireotide, which has a broader affinity for all somatostatin receptor (sst) subtypes compared with the currently available somatostatin analogues with preferential affinity for the sst2 receptor, and chimeric compounds that interact with both somatostatin and dopamine receptors with synergizing effects on GH secretion.
[show abstract][hide abstract] ABSTRACT: Somatotropin-release inhibitory factor (SRIF) is a major regulator of pituitary function, mostly inhibiting hormone secretion and to a lesser extent pituitary cell growth. Five SRIF receptor subtypes (SSTR1-5) are ubiquitously expressed G-protein coupled receptors. In the pituitary, SSTR1, 2, 3 and 5 are expressed, with SSTR2 and SSTR5 predominating. As new SRIF analogs have recently been introduced for treatment of pituitary disease, we evaluate the current knowledge of cell-specific pituitary SRIF receptor signaling and highlight areas of future research for comprehensive understanding of these mechanisms. Elucidating pituitary SRIF receptor signaling enables understanding of pituitary hormone secretion and cell growth, and also encourages future therapeutic development for pituitary disorders.
Trends in Endocrinology and Metabolism 02/2010; 21(3):123-33. · 8.90 Impact Factor
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