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, DooSeok Choi, Adriano B. Tavares, Laurence C. Udoff, Eliahu Levitas, Carol E. Resnick, Ronald (Ron) Rosenfeld, Eli Y. Adashi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
Volume67
Issue number3
DOIs
StatePublished - Sep 2002
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Proteins
Granulosa Cells
Protein Kinase C
Cyclic AMP-Dependent Protein Kinases
Gonadotropin-Releasing Hormone
Acetates
Proteins
Staurosporine
Phorbol Esters
Catalytic Domain
Up-Regulation

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

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. / Chamoun, Diran; Choi, DooSeok; Tavares, Adriano B.; Udoff, Laurence C.; Levitas, Eliahu; Resnick, Carol E.; Rosenfeld, Ronald (Ron); Adashi, Eli Y.

In: Biology of Reproduction, Vol. 67, No. 3, 09.2002, p. 1003-1012.

Research output: Contribution to journalArticle

Chamoun, Diran ; Choi, DooSeok ; Tavares, Adriano B. ; Udoff, Laurence C. ; Levitas, Eliahu ; Resnick, Carol E. ; Rosenfeld, Ronald (Ron) ; Adashi, Eli Y. / 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. In: Biology of Reproduction. 2002 ; Vol. 67, No. 3. pp. 1003-1012.
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AU - Tavares, Adriano B.

AU - Udoff, Laurence C.

AU - Levitas, Eliahu

AU - Resnick, Carol E.

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AU - Adashi, Eli Y.

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AB - 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.

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