Novel function of ovarian growth factors: combined studies by DNA microarray, biochemical and physiological approaches.
Owing to the development of the DNA microarray technique, modulation of gene function can be studied systematically. Considerable attention has been focused on members of the growth factor family to elucidate the main regulators of oocyte maturation and ovarian follicle rupture. Among these growth factors, it was found both in rodents and in humans that amphiregulin (Ar) and epiregulin (Ep) of the epidermal growth factor (EGF) family were dramatically up-regulated by gonadotrophins in the intact ovary and in primary granulosa cells, respectively. Their role in cumulus expansion and oocyte maturation was established in rodents, and their formation under LH stimulation in granulosa cells was demonstrated in humans. To be activated, Ar and Ep must be cleaved by A Disintegrin And Metalloproteinases (ADAMs) family. However, the precise processing of Ar and Ep by the cumulus cells is still obscure. Future investigations using DNA microarray technique may reveal the repertoire of genes activated in Ar- and Ep-stimulated cumulus cells and may help elucidate the molecular basis of ovulation.
Ben-Ami
Ido
I
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Freimann
Sarit
S
Armon
Leah
L
Dantes
Ada
A
Ron-El
Raphael
R
Amsterdam
Abraham
A
D066258:Amphiregulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D066260:Epiregulin; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; C587880:EREG protein, human; D066260:Epiregulin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor