Signal transduction pathways employed by thyrotropin-releasing hormone and pituitary adenylate cyclase activating polypeptide to stimulate prolactin promoter activity.
Item
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Title
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Signal transduction pathways employed by thyrotropin-releasing hormone and pituitary adenylate cyclase activating polypeptide to stimulate prolactin promoter activity.
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Identifier
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AAI9707076
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identifier
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9707076
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Creator
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Chen, Xiaohuai.
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Contributor
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Adviser: Carter Bancroft
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Date
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1996
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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, Molecular | Biology, Cell | Biology, Animal Physiology
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Abstract
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Production of prolactin (PRL), a protein hormone secreted from the anterior pituitary, is regulated by a number of hypothalamic hormones, including thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating peptide (PACAP). Both of them have been shown previously to stimulate PRL promoter activity in rat pituitary GH3 cells.;TRH has been shown to activate phospholipase C and increase the production of both diacylglycerol (DAG) and inositol triphosphate (IP3) in GH3 cells. DAG in turn leads to the activation of protein kinase C, and IP3 causes both the release of Ca{dollar}\sp{lcub}2+{rcub}{dollar} from intracellular stores and activation of Ca{dollar}\sp{lcub}2+{rcub}{dollar}/calmodulin kinase II activity. TRH has also been shown to stimulate phosphorylation of the oncogene raf and to activate mitogen activated protein kinase (MAP kinase) in these cells. Therefore, TRH stimulation of PRL promoter activity might be mediated by either one or a combination of these pathways. In my studies, I have employed pharmacological studies to provide evidence that TRH action is not mediated through either the PKC or the raf/MAP kinase pathways, but instead is mediated via a Ca{dollar}\sp{lcub}2+{rcub}{dollar}-Calmodulin-CaM kinase pathway. My studies also implicate the release of Ca{dollar}\sp{lcub}2+{rcub}{dollar} from intracellular stores in the transcriptional action of TRH.;I then compared the signal transduction pathways employed by TRH and PACAP to regulate PRL promoter activity. Since one of the PACAP receptor subtypes expressed in GH3 cells can stimulate both adenylate cyclase and phospholipase C, PACAP stimulation of the PRL promoter could be mediated via a pathway involving either cAMP or inositol phosphates or both. My finding that optimal concentrations of TRH and PACAP have additive stimulatory effects on PRL promoter activity implied that TRH and PACAP employ different pathways to regulate PRL promoter activity. My observation that both a dominant negative CREB mutant and mutation of a CRE-like element (CLE) in the PRL promoter partially block induction by PACAP, but not by TRH, further suggests that TRH and PACAP employ different pathways to regulate the PRL promoter activity.
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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.
