[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
[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: RATIONALE: Extrapyramidal motor signs are the major features of Parkinson's disease (PD). It is unclear whether there is a link between these signs and such PD-associated factors as brain somatostatin deficiency and aging. OBJECTIVES: This study aimed to examine whether an inhibition of the brain somatostatin system can initiate catalepsy, a model of extrapyramidal disorders, in young and aged rats. METHODS: The animals of 100-110 and 540-560 days of age were used. Catalepsy was measured using the bar test. The inhibition of the brain somatostatin activity was simulated by intracerebroventricular administration of a somatostatin antagonist, cyclosomatostatin. RESULTS: Cyclosomatostatin dose-dependently induced catalepsy in aged, but not in young rats. The cataleptic response was reversed by a somatostatin analog, octreotide. CONCLUSIONS: The combination of aging and brain somatostatin deficiency can lead to catalepsy in rats. Since both factors are frequently observed in PD patients, the present results might be of relevance for pathogenesis of extrapyramidal signs in this disease.
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