Connective tissue growth factor expression in the human corpus luteum: paracrine regulation by human chorionic gonadotropin.
BACKGROUND
The molecular mechanisms of luteolysis and its inhibition during maternal recognition of pregnancy remain unclear.


OBJECTIVE
The objective of this study was to investigate the differential regulation of connective tissue growth factor (CTGF) expression in human corpora lutea using in vivo and in vitro models.


METHODS
Corpora lutea from different stages of the luteal phase and after luteal rescue with human chorionic gonadotropin (hCG) were studied. Primary cultures and cocultures of luteinized granulosa cells and luteal fibroblast-like cells were performed.


METHODS
This study was performed at the research center of a university teaching hospital.


METHODS
Women with regular cycles having hysterectomy for nonmalignant conditions and women undergoing oocyte collection for assisted conception were studied.


METHODS
CTGF localization was determined by in situ hybridization, and expression by quantitative RT-PCR.


RESULTS
The outcome measures were the effect of hCG on the expression and localization of CTGF mRNA in human corpora lutea and the effect of hCG on CTGF expression in primary cultures of luteinized granulosa cells and luteal fibroblast-like cells.


RESULTS
Luteal rescue reduced CTGF expression compared with that in the late luteal phase (P < 0.05). CTGF expression was localized to fibroblast-like cells and endothelial cells of larger blood vessels, not to steroidogenic cells. The expression of CTGF by fibroblast-like cells in vitro was not regulated by hCG. When cocultured with luteinized granulosa cells, fibroblast-like cell CTGF expression was inhibited by hCG (P < 0.001). This effect was independent of stimulated progesterone concentrations and was not blocked by follistatin or indomethacin. Both IL-1alpha (P < 0.05) and cAMP (P < 0.001) inhibited CTGF expression in fibroblast-like cells.


CONCLUSIONS
These results provide evidence for negative regulation of CTGF by hCG during luteal rescue mediated by paracrine signals.
Duncan
W Colin
WC
Department of Reproductive and Developmental Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. w.c.duncan@ed.ac.uk
Hillier
Stephen G
SG
Gay
Eva
E
Bell
Julie
J
Fraser
Hamish M
HM
D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D018920:Coculture Techniques; D055513:Connective Tissue Growth Factor; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019899:Paracrine Communication; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
C526317:CCN2 protein, human; D006063:Chorionic Gonadotropin; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D011374:Progesterone