Regulation of granulosa cell-derived insulin-like growth factor binding proteins (IGFBPs): Role for protein kinase-C in the pre- and posttranslational modulation of IGFBP-4 and IGFBP-5

Diran Chamoun, Doo Seok Choi, Adriano B. Tavares, Laurence C. Udoff, Eliahu Levitas, Carol E. Resnick, Ron G. Rosenfeld, Eli Y. Adashi

Research output: Contribution to journalArticle

4 Scopus citations


A growing body of information suggests antigonadotropic and atretogenic roles for granulosa cell-derived insulin-like growth factor binding proteins (IGFBPs) 4 and 5 during ovarian folliculogenesis. Activation of protein kinase-A (PKA) in rat granulosa cells has been shown to modulate the relative expression of IGFBP-4 and -5 transcripts and proteins. In this article, we assess the role of protein kinase-C (PKC) in this regard. Provision of granulosa cells with phorbol 12-myristate 13-acetate (PMA) (but not 4αPMA, an inert analogue), a tumor-promoting phorbol ester and an established activator of PKC, was without significant effect on the expression of IGFBP-4 transcripts but resulted in biphasic dose-dependent alterations in IGFBP-5 transcripts and in the accumulation of the IGFBP-4 and -5 proteins. Comparable effects were noted for GnRH, an established PKC agonist. Provision of staurosporine, a potent inhibitor of the catalytic subunit of PKC, produced significant dose-dependent decrements in the relative expression of IGFBP-5 transcripts. Treatment with FSH (presumptively PKA-mediated) markedly attenuated the ability of PMA or GnRH to upregulate the accumulation of the IGFBP-5 (but not IGFBP-4) protein. Taken together, our present findings indicate that the modulation of rat ovarian IGFBP-4 and -5 is PKC as well as PKA dependent and that these two signaling pathways interact in a diametrically opposed and antagonistic fashion.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalBiology of reproduction
Issue number3
StatePublished - Sep 1 2002



  • Female reproductive tract
  • Granulosa cells
  • Insulin-like growth factor receptor
  • Kinases
  • Ovary

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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