Please use this identifier to cite or link to this item:
http://hdl.handle.net/10553/53606
Title: | Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulosa cells: Key roles for prostaglandin synthase 2 and progesterone receptor | Authors: | Shimada, Masayuki Hernandez-Gonzalez, Inmaculada Gonzalez-Robayna, Ignacio Richards, JoAnne S. |
Keywords: | Follicle-Stimulating-Hormone Ribonucleic-Acid Expression Luteinizing-Hormone Endoperoxide Synthase-2 Mice Lacking, et al |
Issue Date: | 2006 | Publisher: | 0888-8809 | Journal: | Molecular Endocrinology | Abstract: | The molecular bridges that link the LH surge with functional changes in cumulus cells that possess few LH receptors are being unraveled. Herein we document that epidermal growth factor ( EGF)- like factors amphiregulin ( Areg), epiregulin ( Ereg), and betacellulin ( Btc) are induced in cumulus oocyte complexes ( COCs) by autocrine and paracrine mechanisms that involve the actions of prostaglandins ( PGs) and progesterone receptor ( PGR). Areg and Ereg mRNA and protein levels were reduced significantly in COCs and ovaries collected from prostaglandin synthase 2 ( Ptgs2) null mice and Pgr null ( PRKO) mice at 4 h and 8 h after human chorionic gonadotropin, respectively. In cultured COCs, FSH/forskolin induced Areg mRNA within 0.5 h that peaked at 4 h, a process blocked by inhibitors of p38MAPK ( SB203580), MAPK kinase (MEK) 1 ( PD98059), and PTGS2 ( NS398) but not protein kinase A ( PKA) ( KT5720). Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF receptor tyrosine kinase inhibitor AG1478 ( AG), PD98059, and NS398. PGE2 reversed the inhibitory effects of AG on AREG-induced expression of Areg but not Ptgs2, placing Ptgs2 downstream of EGF-R signaling. Phorbol 12- myristate 13-acetate (PMA) and adenovirally expressed PGRA synergistically induced Areg mRNA in granulosa cells. In COCs, AREG not only induced genes that impact matrix formation but also genes involved in steroidogenesis ( StAR, Cyp11a1) and immune cell-like functions (Pdcd1, Runx1, Cd52). Collectively, FSH-mediated induction of Areg mRNA via p38MAPK precedes AREG induction of Ptgs2 mRNA via ERK1/2. PGs acting via PTGER2 in cumulus cells provide a secondary, autocrine pathway to regulate expression of Areg in COCs showing critical functional links between G protein- coupled receptor and growth factor receptor pathways in ovulating follicles. | URI: | http://hdl.handle.net/10553/53606 | ISSN: | 0888-8809 | DOI: | 10.1210/me.2005-0504 | Source: | Molecular Endocrinology[ISSN 0888-8809],v. 20 (6), p. 1352-1365 |
Appears in Collections: | Artículos |
SCOPUSTM
Citations
352
checked on Mar 30, 2025
WEB OF SCIENCETM
Citations
337
checked on Mar 30, 2025
Page view(s)
64
checked on May 18, 2024
Google ScholarTM
Check
Altmetric
Share
Export metadata
Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.