Regulation of granulosa cell proliferation and EGF-like ligands during the periovulatory interval in monkeys.
BACKGROUND
This study seeks to clarify cell cycle dynamics of granulosa cells following hCG and elucidate the expression of epidermal growth factor (EGF)-like ligands during luteinization.


METHODS
Granulosa cells were obtained from rhesus macaques undergoing controlled ovarian stimulation protocols before or after an ovulatory hCG bolus. Cell cycle characteristics were determined by flow cytometry and levels of EGF receptor (EGFR), amphiregulin (AREG), epiregulin (EREG) and betacellulin (BTC) mRNAs were measured by real-time RT-PCR.


RESULTS
The proportion of cells in S-phase was 7.5% prior to hCG and did not decline until 24 h after hCG (3.1%). EGFR protein and BTC mRNA did not change following hCG, whereas AREG and EREG mRNA increased starting at 3 and 12 h post-hCG, respectively, and remained elevated thereafter.


CONCLUSIONS
Cell cycle transit of macaque granulosa cells does not change until 24 h after an ovulatory stimulus, whereas the EGF-like ligands EREG and AREG are increased rapidly. This suggests that luteinizing granulosa cells are refractory to mitogenic stimulation by EGFR ligands.
Fru
K N
KN
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Cherian-Shaw
M
M
Puttabyatappa
M
M
VandeVoort
C A
CA
Chaffin
C L
CL
D066258:Amphiregulin; D000818:Animals; D066259:Betacellulin; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066260:Epiregulin; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism*; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008183:Luteal Phase / Q000378:metabolism; D008253:Macaca mulatta; D010060:Ovulation / Q000378:metabolism*; D010062:Ovulation Induction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism
D066258:Amphiregulin; D066259:Betacellulin; D006063:Chorionic Gonadotropin; D066260:Epiregulin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors