GnRH actions on rat preovulatory follicles are mediated by paracrine EGF-like factors

Gonadotropin releasing hormone (GnRH) has been shown to mimic the actions of LH/hCG on oocyte maturation and ovulation. Recent studies demonstrated that induction of ovulation by LH/hCG is mediated, at least in part, by transactivation of epidermal growth factor receptors (EGFR) by autocrine/paracri...

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Veröffentlicht in:Molecular reproduction and development 2006-10, Vol.73 (10), p.1271-1276
Hauptverfasser: Motola, Shmulik, Cao, Xiumei, Ashkenazi, Helena, Popliker, Malka, Tsafriri, Alex
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container_end_page 1276
container_issue 10
container_start_page 1271
container_title Molecular reproduction and development
container_volume 73
creator Motola, Shmulik
Cao, Xiumei
Ashkenazi, Helena
Popliker, Malka
Tsafriri, Alex
description Gonadotropin releasing hormone (GnRH) has been shown to mimic the actions of LH/hCG on oocyte maturation and ovulation. Recent studies demonstrated that induction of ovulation by LH/hCG is mediated, at least in part, by transactivation of epidermal growth factor receptors (EGFR) by autocrine/paracrine EGF‐like factors activated by metalloproteases. Here we have examined whether the action of GnRH on the preovulatory follicles is exerted through similar mechanisms involving activation of EGFR. The EGFR kinase inhibitor, AG1478, inhibited GnRH‐induced oocyte maturation in explanted follicles in vitro. Its inactive analog, AG43, did not affect GnRH‐stimulated resumption of meiosis. GnRH, like LH, stimulated transient follicular expression of EGF‐like agents, as well as rat cycloxygenase‐2 (rCOX‐2), rat hyaluronan synthase‐2 (rHAS‐2), and rat tumor necrosis factor‐α‐stimulated gene 6 (rTSG‐6) mRNAs, known ovulatory enzymes. Likewise, GnRH stimulated follicular progesterone synthesis. Conversely AG1478 inhibited all these actions of GnRH. Furthermore, Galardin, a broad‐spectrum metalloprotease inhibitor, blocked GnRH‐induced oocyte maturation and follicular progesterone synthesis. In conclusion, we have demonstrated that follicular EGF‐like factors mediate also the GnRH‐stimulation of ovulatory changes, like these of LH/hCG. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
doi_str_mv 10.1002/mrd.20556
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Recent studies demonstrated that induction of ovulation by LH/hCG is mediated, at least in part, by transactivation of epidermal growth factor receptors (EGFR) by autocrine/paracrine EGF‐like factors activated by metalloproteases. Here we have examined whether the action of GnRH on the preovulatory follicles is exerted through similar mechanisms involving activation of EGFR. The EGFR kinase inhibitor, AG1478, inhibited GnRH‐induced oocyte maturation in explanted follicles in vitro. Its inactive analog, AG43, did not affect GnRH‐stimulated resumption of meiosis. GnRH, like LH, stimulated transient follicular expression of EGF‐like agents, as well as rat cycloxygenase‐2 (rCOX‐2), rat hyaluronan synthase‐2 (rHAS‐2), and rat tumor necrosis factor‐α‐stimulated gene 6 (rTSG‐6) mRNAs, known ovulatory enzymes. Likewise, GnRH stimulated follicular progesterone synthesis. Conversely AG1478 inhibited all these actions of GnRH. Furthermore, Galardin, a broad‐spectrum metalloprotease inhibitor, blocked GnRH‐induced oocyte maturation and follicular progesterone synthesis. In conclusion, we have demonstrated that follicular EGF‐like factors mediate also the GnRH‐stimulation of ovulatory changes, like these of LH/hCG. Mol. Reprod. 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Reprod. Dev</addtitle><description>Gonadotropin releasing hormone (GnRH) has been shown to mimic the actions of LH/hCG on oocyte maturation and ovulation. Recent studies demonstrated that induction of ovulation by LH/hCG is mediated, at least in part, by transactivation of epidermal growth factor receptors (EGFR) by autocrine/paracrine EGF‐like factors activated by metalloproteases. Here we have examined whether the action of GnRH on the preovulatory follicles is exerted through similar mechanisms involving activation of EGFR. The EGFR kinase inhibitor, AG1478, inhibited GnRH‐induced oocyte maturation in explanted follicles in vitro. Its inactive analog, AG43, did not affect GnRH‐stimulated resumption of meiosis. GnRH, like LH, stimulated transient follicular expression of EGF‐like agents, as well as rat cycloxygenase‐2 (rCOX‐2), rat hyaluronan synthase‐2 (rHAS‐2), and rat tumor necrosis factor‐α‐stimulated gene 6 (rTSG‐6) mRNAs, known ovulatory enzymes. Likewise, GnRH stimulated follicular progesterone synthesis. Conversely AG1478 inhibited all these actions of GnRH. Furthermore, Galardin, a broad‐spectrum metalloprotease inhibitor, blocked GnRH‐induced oocyte maturation and follicular progesterone synthesis. In conclusion, we have demonstrated that follicular EGF‐like factors mediate also the GnRH‐stimulation of ovulatory changes, like these of LH/hCG. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.</description><subject>amphiregulin</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Dipeptides - pharmacology</subject><subject>EGFR transactivation</subject><subject>Epidermal Growth Factor - genetics</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>epiregulin</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. 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Reprod. Dev</addtitle><date>2006-10</date><risdate>2006</risdate><volume>73</volume><issue>10</issue><spage>1271</spage><epage>1276</epage><pages>1271-1276</pages><issn>1040-452X</issn><eissn>1098-2795</eissn><coden>MREDEE</coden><abstract>Gonadotropin releasing hormone (GnRH) has been shown to mimic the actions of LH/hCG on oocyte maturation and ovulation. Recent studies demonstrated that induction of ovulation by LH/hCG is mediated, at least in part, by transactivation of epidermal growth factor receptors (EGFR) by autocrine/paracrine EGF‐like factors activated by metalloproteases. Here we have examined whether the action of GnRH on the preovulatory follicles is exerted through similar mechanisms involving activation of EGFR. The EGFR kinase inhibitor, AG1478, inhibited GnRH‐induced oocyte maturation in explanted follicles in vitro. Its inactive analog, AG43, did not affect GnRH‐stimulated resumption of meiosis. GnRH, like LH, stimulated transient follicular expression of EGF‐like agents, as well as rat cycloxygenase‐2 (rCOX‐2), rat hyaluronan synthase‐2 (rHAS‐2), and rat tumor necrosis factor‐α‐stimulated gene 6 (rTSG‐6) mRNAs, known ovulatory enzymes. Likewise, GnRH stimulated follicular progesterone synthesis. Conversely AG1478 inhibited all these actions of GnRH. Furthermore, Galardin, a broad‐spectrum metalloprotease inhibitor, blocked GnRH‐induced oocyte maturation and follicular progesterone synthesis. In conclusion, we have demonstrated that follicular EGF‐like factors mediate also the GnRH‐stimulation of ovulatory changes, like these of LH/hCG. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16865724</pmid><doi>10.1002/mrd.20556</doi><tpages>6</tpages></addata></record>
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subjects amphiregulin
Animals
Biological and medical sciences
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cyclooxygenase 2 - genetics
Cyclooxygenase 2 - metabolism
Dipeptides - pharmacology
EGFR transactivation
Epidermal Growth Factor - genetics
Epidermal Growth Factor - metabolism
epiregulin
Female
Fundamental and applied biological sciences. Psychology
Glucuronosyltransferase - genetics
Glucuronosyltransferase - metabolism
Gonadotropin-Releasing Hormone - pharmacology
Hormone metabolism and regulation
Hyaluronan Synthases
Mammalian female genital system
Meiosis
Ovarian Follicle - drug effects
Ovarian Follicle - growth & development
Ovarian Follicle - metabolism
Ovulation
Phosphorylation
Progesterone - biosynthesis
Protein Kinase Inhibitors - pharmacology
Quinazolines
Rats
Rats, Wistar
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - metabolism
resumption of meiosis
RNA, Messenger - metabolism
Signal Transduction
Tyrphostins - pharmacology
Vertebrates: reproduction
title GnRH actions on rat preovulatory follicles are mediated by paracrine EGF-like factors
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