EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells.
Epiregulin and amphiregulin are growth factors involved in cancer development, but their potential role in signaling in the gonads is still obscure. We report here that basal expression of these growth factors is evident in human granulosa cells obtained from women treated for in vitro fertilization, when examined by RT-PCR using RNA isolated from primary cultures of ovarian granulosa cells. Expression of these factors was elevated concomitantly with elevation of progesterone production in these cells upon stimulation with luteinizing hormone (LH), and to a lesser extent with follicle stimulating hormone (FSH), both essential stimulants for ovulation and luteinization. Epiregulin and amphiregulin gene expression was dose- and time-dependent when measured subsequent to LH stimulation. Moreover, forskolin, which activates adenylate cyclase, was as efficient as LH in stimulating expression of these growth factors. It is suggested that upregulation of the epiregulin and amphiregulin expression is part of the signal transduction pathway which leads to ovulation and luteinization in the human ovary.
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
S
S
Freimann
I
I
Ben-Ami
A
A
Dantes
R
R
Ron-El
A
A
Amsterdam
D066258:Amphiregulin; D015153:Blotting, Western; D002478:Cells, Cultured; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D066260:Epiregulin; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry; D006062:Gonadotropins / Q000737:chemistry*; D006107:Granulosa Cells / Q000166:cytology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000737:chemistry; D007986:Luteinizing Hormone / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D011374:Progesterone / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; C587880:EREG protein, human; D066260:Epiregulin; D006023:Glycoproteins; D006062:Gonadotropins; D036341:Intercellular Signaling Peptides and Proteins; D005576:Colforsin; D011374:Progesterone; D004815:Epidermal Growth Factor; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP