Abstract. During in vitro maturation of porcine cumulus-oocyte complexes (COCs), progesterone was secreted from cumulus cells and acted on the cumulus cells themselves, which required for cumulus expansion and oocyte maturation. EGF-like factor (amphiregulin, AREG; epiregulin, EREG) and its protease, TACE/ADAM17, are also expressed in cumulus cells, and thereby, soluble EGF domain was acted on the EGF receptor expressed on cumulus cells. In this study, we examined the relationship between progesterone function and EGF-like factor stimuli in cumulus cells of porcine COCs. When COCs were cultured with FSH and LH, Areg, Ereg and Tace/Adam17 were expressed in cumulus cells. Treatment with a progesterone receptor (PGR) antagonist, RU486, did not affect the Areg and Ereg mRNA expression levels at any culture time points. However, the Tace/Adam17 mRNA level, protein level and its activity were significantly suppressed by RU486 at the 30 or 40 h time point. At 20 h of culture, phosphorylation of ERK1/2 and the expressions of target genes (Has2, Tnfaip6 and Ptgs2) were not suppressed by RU486; however, at 40 h, ERK1/2 phosphorylation and the target gene expression levels were significantly downregulated by RU486 in cumulus cells. Furthermore, the negative effects of RU486 at 40 h were overcome by the addition of EGF. These results indicated that the level of TACE/ADAM17 in cumulus cells was regulated by the progesterone-PGR pathway during in vitro maturation of porcine COCs. Therefore, we concluded that the progesterone-induced TACE/ADAM17 leads to production of soluble EGF domain from cumulus cells, which enhances functional changes of cumulus cells and progresses meiotic maturation of oocytes during in vitro maturation of porcine COCs. Key words: Cumulus expansion, EGF-like factor, Oocyte maturation (J. Reprod. Dev. 56: [315][316][317][318][319][320][321][322][323] 2010) n mammals, the LH surge acted on granulosa cells, and induced the ovulation process. During this period, the estrogen concentration was decreased, whereas the progesterone concentration was risen in follicular fluid concomitantly with the downregulation of Cyp19a1 mRNA and upregulation of Cyp11a1 and Hsd3b1 mRNA in granulosa and/or cumulus cells [1,2]. Numerous functions of progesterone were mediated by the intracellular receptor, progesterone receptor (PGR) [3][4][5]. PGR was induced in the granulosa cells of the rat preovulatory follicle by LH [6,7]. Pgr knockout mice (PRKO) fail to ovulate [8,9], indicating that the progesterone-dependent pathway played a critical role in functional change of follicular cells during the ovulatory process.The EGF-like factor (amphiregulin, AREG; Epiregulin, EREG;ÎČ-cellulin, BTC) is expressed in granulosa cells and cumulus cells in the rodent and pig in response to ovulational stimuli [10,11]. The cleaved enzyme of EGF-like factor, TACE/ADAM17, is also expressed in porcine granulosa cells after hCG administration in vivo [12]. Since double-mutant mice with null that are Areg and homozygous for the Egfr wa2 allele (...