The role of endopeptidase 24.15 in the metabolism of LHRH.
Item
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Title
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The role of endopeptidase 24.15 in the metabolism of LHRH.
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Identifier
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AAI9020776
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identifier
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9020776
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Creator
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Lasdun, Abraham M.
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Contributor
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Adviser: Marian Orlowski
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Date
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1990
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Animal Physiology | Biology, General
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Abstract
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Inhibitors of endopeptidase-24.15 (EP-24.15) a zinc-containing metalloendopeptidase, cleaves the Tyr{dollar}\sp 5{dollar}-Gly{dollar}\sp 6{dollar} bond of luteinizing hormone releasing-hormone (LHRH) were used to probe the role of this enzyme in the in vivo metabolism of LHRH and its role in regulating the response of pituitary gonadotropes to LHRH. Inhibitors of EP-24.15 are also shown to block the in vivo degradation of intracerebroventricularly (ICV) and intravenously (IV) administered LHRH. Concurrent ICV administration of LHRH and a specific inhibitor of EP-24.15, led to a more than 10-fold increase in LHRH recovery above controls treated with LHRH alone. In addition, IV administration of LHRH and EP-24.15 inhibitor, resulted in a dramatic 8-fold increase in the half-life of LHRH from 10 min to 80 min, similar to values reported for superactive LHRH analogs.;Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations were also measured in rats after ICV and IV administration of LHRH alone or in conjunction with inhibitors of EP-24.15. In animals treated with two potent EP-24.15 inhibitors, IV and ICV LHRH injections induced a much greater and longer-lasting increase of plasma LH and FSH concentrations than in controls receiving LHRH alone. The magnitude and duration of the increases was similar to those after administration of two superactive LHRH analogs.;It is concluded that: (1) EP-24.15 is the dominant factor determining the in vivo LHRH degradation both in the CNS and periphery; (2) LHRH degradation by EP-24.15 limits the magnitude and duration of the response of the pituitary to LHRH; and (3) the increased in vivo activity of the "superactive" LHRH analogs can largely be attributed to their resistance to degradation by EP-24.15.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
