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001-es BibID:BIBFORM033606
035-os BibID:WOS:000173450100076
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Changes in subcellular distribution of pituitary receptors for luteinizing hormone-releasing hormone (LH-RH) after treatment with the LH-RH antagonist cetrorelix / Gabor Halmos, Andrew V. Schally
Dátum:2002
ISSN:0027-8424
Megjegyzések:Treatment with antagonists of luteinizing hormone-releasing hormone (LH-RH) leads to down-regulation of pituitary LH-RH receptors. Thus, the effect of LH-RH antagonists is similar to that of the LH-RH agonists, but the mode of action of antagonists is not completely understood. The aim of this study was to investigate the effects of LH-RH antagonist cetrorelix on the binding characteristics and subcellular localization of receptors for LH-RH in rat pituitaries. Radioligand binding studies, performed after in vitro desaturation, revealed that a single s.c. injection of cetrorelix at a dose of 100 mug per rat significantly decreased the number of pituitary membrane receptors for LH-RH in a time-dependent manner with the nadir occurring at 6 h. In contrast, 2-6 h after cetrorelix treatment, the concentration of binding sites for LH-RH in the nuclei of rat pituitaries was significantly higher (P < 0.01) than in controls, Chronic administration of cetrorelix also decreased the level of membrane receptors for LH-RH by 83% (P < 0.01) after 7 days, and 86% (P < 0.01) after 14 days. The number of LH-RH binding sites in the nuclear pellet was increased 3-fold (P < 0.01) by days 7 and 14 after the initiation of treatment with cetrorelix. A single injection or prolonged treatment with LH-RH antagonist also decreased the mRNA expression of pituitary receptors for LH-RH. Our results demonstrate that the down-regulation of LH-RH receptors on the cell membranes of rat pituitaries after therapy with antagonist cetrorelix is associated with an increase in receptor concentration in the nuclei. These phenomena could be related to the internalization and subcellular translocation of LH-RH receptors.
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Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 99 : 2 (2002), p. 961-965. -
További szerzők:Schally, Andrew Victor
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