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Title: Effect of the protein phosphatase inhibitor okadaic acid on FSH-induced granulosa cell steroidogenesis
Authors: González Reyes, J.
Santana, P. 
González Robaina, I. 
Cabrera Oliva, J.
Estévez, F. 
Hernandez, I 
López Blanco, F. 
Quintana Aguiar, J. 
Fanjul, L. F. 
Ruiz De Galarreta, C. M.
UNESCO Clasification: 32 Ciencias médicas
320502 Endocrinología
Keywords: Gonadotropin-Releasing Hormone
Tumor Promoter
Phorbol Ester
Coordinated Regulation, et al
Issue Date: 1997
Publisher: 0022-0795
Journal: Journal of Endocrinology 
Abstract: To address a possible role of type 1 and 2A serine/threonine protein phosphatases (PP1 and PP2A) in regulating granulosa cell hormonal responses, we investigated the effects of okadaic acid (OA) on FSH- and cAMP-induced steroidogenesis in these cells. When added alone (0.01-1 nmol/l), the cell-permeant phosphatase inhibitor did not affect progesterone and 3 beta-hydroxysteroid dehydrogenase/Delta(5-4) isomerase (3 beta-HSD) enzyme activity, whereas when added with FSH it dose-dependently augmented (minimal effective dose, 0.1 nmol/l) gonadotropin-stimulated steroidogenesis in cultured granulosa cells. A similar stimulatory effect of the toxin was observed in cells cultured for 48 h with the cell-permeant analogue dibutyryl cAMP (1 mmol/l), or when granulosa cells were stimulated with the cAMP-inducing agents cholera toxin (1 mu g/ml), forskolin (15 mu mol/l) or 1-methyl-3-isobutyl-xanthine (0.1 mmol/l). The observed effect of OA on FSH-supported granulosa cell steroidogenesis was not a consequence of increased cAMP generation, and time course experiments also revealed that a minimal time period of 12 h was necessary for OA (0.1 and 1 nmol/l) to significantly enhance FSH-induced progesterone and 3 beta-HSD enzyme activity. Since OA also inhibits the dephosphorylation of protein kinase C (PKC) substrates, we also compared the effect of OA and the PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) on FSH-induced granulosa cell steroidogenic activity. While activation of the PKC pathway with the tumor promoter TPA (10 nmol/l) inhibited progesterone and cAMP accumulation in FSH-stimulated granulosa cells, treatment with OA augmented steroidogenesis and did not affect gonadotropin-induced cAMP generation. Collectively these results suggest that PP1 and PP2A may be important in regulating the phosphorylation state of proteins implicated in the cAMP-protein kinase A-stimulated steroidogenic activity of these cells.
ISSN: 0022-0795
Source: Journal of Endocrinology[ISSN 0022-0795],v. 152, p. 131-139 (Enero 1997)
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