The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells.
We examine the pathways involved in the luteinizing hormone receptor (LHR)-dependent activation of the epidermal growth factor (EGF) network using cocultures of LHR-positive granulosa cells and LHR-negative test cells expressing an EGF receptor (EGFR)-green fluorescent protein fusion protein. Activation of the LHR in granulosa cells results in the release of EGF-like growth factors that are detected by measuring the phosphorylation of the EGFR-green fluorescent protein expressed only in the LHR-negative test cells. Using neutralizing antibodies and real-time PCR, we identified epiregulin as the main EGF-like growth factor produced upon activation of the LHR expressed in immature rat granulosa cells, and we show that exclusive inhibition or activation of the ERK1/2 cascade in granulosa cells prevents or enhances epiregulin release, respectively, with little or no effect on epiregulin expression. These results show that the LHR-stimulated ERK1/2 pathway stimulates epiregulin release.
Andric
Nebojsa
N
Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
Ascoli
Mario
M
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066260:Epiregulin; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D045726:Metalloproteases / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011974:Receptors, LH / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D066260:Epiregulin; C587882:Ereg protein, rat; D011974:Receptors, LH; D004815:Epidermal Growth Factor; C483803:Egfr protein, rat; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D045726:Metalloproteases