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The role of adenosine triphosphate in human granulosa -luteal cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The role of adenosine triphosphate in human granulosa -luteal cells./
Author:	Tai, Chen-Jei.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2001,
Description:	225 p.
Notes:	Source: Dissertations Abstracts International, Volume: 63-06, Section: B.
Contained By:	Dissertations Abstracts International63-06B.
Subject:	Obstetrics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NQ61180
ISBN:	9780612611801

The role of adenosine triphosphate in human granulosa -luteal cells.
Tai, Chen-Jei.

The role of adenosine triphosphate in human granulosa -luteal cells. - Ann Arbor : ProQuest Dissertations & Theses, 2001 - 225 p.

Source: Dissertations Abstracts International, Volume: 63-06, Section: B.

Thesis (Ph.D.)--The University of British Columbia (Canada), 2001.

This item must not be sold to any third party vendors.

Adenosine triphosphate (ATP) is released from cells such as platelets and co-released with neurotransmitter granules from autonomic nerves by exocytosis. Extracellular ATP binds to a G protein-coupled P2 purinoceptor that activates phospholipase C and phosphatidylinositol hydrolysis, generating diacylglycerol and inositol 1,4,5-trisphosphate, which stimulate protein kinase C (PKC) and cytosolic calcium mobilization, respectively. Autonomic nerves have been shown to innervate the ovary and may be involved in regulating steroidogenesis. It is tempting to speculate that the co-released ATP from autonomic nerve endings in the ovary may play a role in regulating ovarian function. A series of experiments has been performed in this study to examine (1) the expression and regulation of P2U purinergic receptor (P2UR) in human granulosa-luteal cells (hGLCs), (2) the role of PKC in ATP-induced calcium oscillations, (3) the action and mechanism of antigonadotropic effect of ATP on hGLCs, (4) the functional role of extracellular ATP in the ovary, and (5) the effect of ATP on the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in hGLCs. This study demonstrated for the first time the expression of P2UR mRNA in hGLCs, and the regulation of P2UR mRNA by hCG, cAMP and forskolin. The P2UR was functional in hGLCs, since activation of the P2UR by ATP or UTP resulted in rapid and transient mobilization of cytosolic calcium at the single cell level. It appears that PKC may have dual actions by providing positive forward actions as well as negative feedback in controlling various signaling steps. As shown in this study, ATP was capable of inducing calcium mobilization, which was negatively regulated by PKC, from both intracellular stores and extracellular influx in cultured hGLCs. The antigonadotropic effect of extracellular ATP was revealed as it significantly reduced hCG-stimulated cAMP production. The inhibitory effect of ATP was reversed by PKC inhibitors, staurosporin and bisindolymaleimide I, indicating the involvement of PKC in mediating the antigonadotropic action of ATP in hGLCs. Further, our data demonstrated that ATP was able to activate the MAPK signaling pathway in hGLCs. After binding to P2-purinoceptor, ATP activated MAPK subsequent to PLC and PKC activation through a PTX-insensitive G-protein in hGLCs. MAPK mediated the anti-gonadotropic action of ATP in steroidogenesis by reducing hCG-stimulated progesterone production. These findings support a potential role of ATP in regulating ovarian function.

ISBN: 9780612611801Subjects--Topical Terms:

634501
Obstetrics.
Subjects--Index Terms:

Adenosine triphosphate

The role of adenosine triphosphate in human granulosa -luteal cells.
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100 1 $a Tai, Chen-Jei. $3 3683558
245 1 4 $a The role of adenosine triphosphate in human granulosa -luteal cells.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2001
300 $a 225 p.
500 $a Source: Dissertations Abstracts International, Volume: 63-06, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Leung, C. K.
502 $a Thesis (Ph.D.)--The University of British Columbia (Canada), 2001.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a Adenosine triphosphate (ATP) is released from cells such as platelets and co-released with neurotransmitter granules from autonomic nerves by exocytosis. Extracellular ATP binds to a G protein-coupled P2 purinoceptor that activates phospholipase C and phosphatidylinositol hydrolysis, generating diacylglycerol and inositol 1,4,5-trisphosphate, which stimulate protein kinase C (PKC) and cytosolic calcium mobilization, respectively. Autonomic nerves have been shown to innervate the ovary and may be involved in regulating steroidogenesis. It is tempting to speculate that the co-released ATP from autonomic nerve endings in the ovary may play a role in regulating ovarian function. A series of experiments has been performed in this study to examine (1) the expression and regulation of P2U purinergic receptor (P2UR) in human granulosa-luteal cells (hGLCs), (2) the role of PKC in ATP-induced calcium oscillations, (3) the action and mechanism of antigonadotropic effect of ATP on hGLCs, (4) the functional role of extracellular ATP in the ovary, and (5) the effect of ATP on the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in hGLCs. This study demonstrated for the first time the expression of P2UR mRNA in hGLCs, and the regulation of P2UR mRNA by hCG, cAMP and forskolin. The P2UR was functional in hGLCs, since activation of the P2UR by ATP or UTP resulted in rapid and transient mobilization of cytosolic calcium at the single cell level. It appears that PKC may have dual actions by providing positive forward actions as well as negative feedback in controlling various signaling steps. As shown in this study, ATP was capable of inducing calcium mobilization, which was negatively regulated by PKC, from both intracellular stores and extracellular influx in cultured hGLCs. The antigonadotropic effect of extracellular ATP was revealed as it significantly reduced hCG-stimulated cAMP production. The inhibitory effect of ATP was reversed by PKC inhibitors, staurosporin and bisindolymaleimide I, indicating the involvement of PKC in mediating the antigonadotropic action of ATP in hGLCs. Further, our data demonstrated that ATP was able to activate the MAPK signaling pathway in hGLCs. After binding to P2-purinoceptor, ATP activated MAPK subsequent to PLC and PKC activation through a PTX-insensitive G-protein in hGLCs. MAPK mediated the anti-gonadotropic action of ATP in steroidogenesis by reducing hCG-stimulated progesterone production. These findings support a potential role of ATP in regulating ovarian function.
590 $a School code: 2500.
650 4 $a Obstetrics. $3 634501
650 4 $a Gynecology. $3 618102
653 $a Adenosine triphosphate
653 $a Granulosa-luteal cells
653 $a P2U purinergic receptor
653 $a Protein kinase C
690 $a 0380
690 $a 0380
710 2 $a The University of British Columbia (Canada). $3 626643
773 0 $t Dissertations Abstracts International $g 63-06B.
790 $a 2500
791 $a Ph.D.
792 $a 2001
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NQ61180