Molecular Human Reproduction, Vol. 8, No. 2, 136-141,
February 2002
© 2002 European Society of Human Reproduction and Embryology
Ovary and oogenesis |
Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa–luteal cells
1 Department of Pathology, P.O.Box 21, University of Helsinki, FIN-00014 Helsinki, 2 Department of Paediatrics and 3 Department of Pathology and Forensic Medicine, P.O.Box 1777, Kuopio University Hospital and University of Kuopio, FIN-70211 Kuopio and 4 Department of Obstetrics and Gynaecology, P.O.Box 140, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland
Insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) have been shown to be involved in ovarian follicular growth/development and steroidogenesis. Recently, a number of low-affinity IGFBP-related proteins (IGFBP-rP) have been characterized. In this study, we investigated the expression of the gene for IGFBP-rP2 (also known as connective tissue growth factor, CTGF) in human granulosa cells in vitro and in vivo. Northern blot analysis demonstrated that IGFBP-rP2 mRNA is expressed in cultured human granulosa–luteal cells obtained from women undergoing an IVF programme. Accumulation of IGFBP-rP2 mRNA was dose-dependently down-regulated by FSH and LH after 24 h treatment (both P < 0.05) in cultured granulosa–luteal cells. The inhibitory effects of gonadotrophins were mimicked by treatment with the protein kinase A activator, (Bu)2cAMP. Protein kinase C inhibitor staurosporine reduced, whereas protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) increased, IGFBP-rP2 mRNA accumulation. These results suggest that the inhibitory effects of gonadotrophins on IGFBP-rP2 gene expression may involve signal transduction via both protein kinase A and C pathways. Immunohistochemical analysis revealed positive staining for IGFBP-rP2 in the granulosa and theca cells of normal human ovarian follicles. Corpus luteum and ovarian surface epithelial cells were also positively stained. Modulation of IGFBP-rP2 expression by gonadotrophic hormones may have a role in ovarian follicular development and in the ovulatory process.
gonadotrophin/granulosa-luteal/IGFBP-rP/ovary/protein kinase
5 To whom correspondence should be addressed. E-mail: Jiangi.Liu{at}helsinki.fi
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