The effects of growth factors and phorbol esters on steroid biosynthesis in isolated human theca interna and granulosa-lutein cells in long term culture

Janette McAllister, W. Byrd, Evan R. Simpson

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Abstract

In this report we examined the effects of growth factors and phorbol esters on steroid hydroxylase activity in cultured human thecal and granulosa-lutein cells. Treatment of thecal cells with epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-β (TGFβ), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17α-hydroxylase activity and 17α-hydroxyprogesterone and dehydroepiandrosterone production. In contrast, cAMP-stimulated 3β-hydroxysteroid dehydrogenase (3βHSD) activity was enhanced by FGF and TGFβ, and treatment with EGF enhanced cAMP-stimulated progesterone production. cAMP stimulated 3βHSD activity was unaffected by TPA (10 nmol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone production. Basal 3βHSD activity and progesterone production were inhibited by TPA. In contrast to the inhibitory actions of EGF, FGF, and TGFβ on 17α- hydroxylase expression, insulin and insulin-like growth factor-I enhanced forskolin-stimulated 17α-hydroxylase activity. In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA. TGFβ had no effect on forskolin-stimulated aromatase activity. EGF, FGF, and TGFβ did not affect forskolin-stimulated progesterone production, whereas treatment with TPA inhibited cAMP-stimulated progesterone secretion. These data suggest that growth factors may differentially regulate cAMP dependent processes in human thecal and granulosa cells of the developing follicle.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume79
Issue number1
DOIs
StatePublished - Jan 1 1994

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Theca Cells
Luteal Cells
Lutein
Biosynthesis
Phorbol Esters
Fibroblast Growth Factors
Transforming Growth Factors
Colforsin
Intercellular Signaling Peptides and Proteins
Epidermal Growth Factor
Acetates
3-Hydroxysteroid Dehydrogenases
Steroids
Progesterone
Mixed Function Oxygenases
Aromatase
Steroid Hydroxylases
17-alpha-Hydroxyprogesterone
Dehydroepiandrosterone
Granulosa Cells

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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abstract = "In this report we examined the effects of growth factors and phorbol esters on steroid hydroxylase activity in cultured human thecal and granulosa-lutein cells. Treatment of thecal cells with epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-β (TGFβ), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17α-hydroxylase activity and 17α-hydroxyprogesterone and dehydroepiandrosterone production. In contrast, cAMP-stimulated 3β-hydroxysteroid dehydrogenase (3βHSD) activity was enhanced by FGF and TGFβ, and treatment with EGF enhanced cAMP-stimulated progesterone production. cAMP stimulated 3βHSD activity was unaffected by TPA (10 nmol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone production. Basal 3βHSD activity and progesterone production were inhibited by TPA. In contrast to the inhibitory actions of EGF, FGF, and TGFβ on 17α- hydroxylase expression, insulin and insulin-like growth factor-I enhanced forskolin-stimulated 17α-hydroxylase activity. In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA. TGFβ had no effect on forskolin-stimulated aromatase activity. EGF, FGF, and TGFβ did not affect forskolin-stimulated progesterone production, whereas treatment with TPA inhibited cAMP-stimulated progesterone secretion. These data suggest that growth factors may differentially regulate cAMP dependent processes in human thecal and granulosa cells of the developing follicle.",
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N2 - In this report we examined the effects of growth factors and phorbol esters on steroid hydroxylase activity in cultured human thecal and granulosa-lutein cells. Treatment of thecal cells with epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-β (TGFβ), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17α-hydroxylase activity and 17α-hydroxyprogesterone and dehydroepiandrosterone production. In contrast, cAMP-stimulated 3β-hydroxysteroid dehydrogenase (3βHSD) activity was enhanced by FGF and TGFβ, and treatment with EGF enhanced cAMP-stimulated progesterone production. cAMP stimulated 3βHSD activity was unaffected by TPA (10 nmol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone production. Basal 3βHSD activity and progesterone production were inhibited by TPA. In contrast to the inhibitory actions of EGF, FGF, and TGFβ on 17α- hydroxylase expression, insulin and insulin-like growth factor-I enhanced forskolin-stimulated 17α-hydroxylase activity. In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA. TGFβ had no effect on forskolin-stimulated aromatase activity. EGF, FGF, and TGFβ did not affect forskolin-stimulated progesterone production, whereas treatment with TPA inhibited cAMP-stimulated progesterone secretion. These data suggest that growth factors may differentially regulate cAMP dependent processes in human thecal and granulosa cells of the developing follicle.

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