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Differential regulation of inhibin/activin alpha- and beta A-subunit and follistin mRNAs by cyclic AMP and phorbol ester in cultured human granulosa-luteal cells.

Abstract：

:Granulosa cell-derived inhibin A (a dimer of alpha- and beta A-subunits), activin A (a homodimer of beta A-subunits) and the activin-binding protein follistatin are important regulators of human ovarian steroidogenesis. We here studied how 8-bromo-cAMP (8br-cAMP), a protein kinase A activator, and 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C activator, affect the steady-state levels of alpha- and beta A-subunit and follistatin mRNAs in cultured human granulosa-luteal cells. 8br-cAMP induced alpha- and beta A-subunit and follistatin steady-state mRNA levels in a time- and concentration-dependent manner. The levels of alpha-subunit mRNAs were stimulated by 8br-cAMP in a sustained manner with a maximal induction seen at the time points 24 and 48 h. By contrast, beta A-subunit and follistatin mRNA levels were rapidly and transiently induced by 8br-cAMP with maximal effects observed at 3 h and 8 h, respectively. TPA did not affect basal alpha-subunit mRNA levels but it rapidly induced beta A-subunit mRNAs at 3 h and the stimulation was still evident at 48 h. TPA induced follistatin mRNA levels with kinetics similar to 8br-cAMP but to a lesser extent. Moreover, 8br-cAMP and TPA stimulated beta A-subunit and follistatin mRNA levels synergistically at 3 h. By contrast, TPA had a potent inhibitory effect on 8br-cAMP- and hCG-induced alpha-subunit levels. Neither 8br-cAMP nor TPA regulated inhibin/activin beta B-subunit mRNA levels. Taken together the activation of protein kinase-A and -C by 8br-cAMP and TPA, respectively, lead to clearly differential responses in the steady-state levels of inhibin activin alpha- and beta A-subunit and follistatin mRNAs. These results suggest that the inhibin A vs. activin A ratio as well as follistatin levels are regulated by multiple second-messenger pathways in the human ovary.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Tuuri T,Erämaa M,Van Schaik RH,Ritvos O

doi

10.1016/0303-7207(96)03842-7

subject

Has Abstract

pub_date

1996-07-23 00:00:00

pages

1-10

issue

eissn

0303-7207

issn

1872-8057

pii

0303720796038427

journal_volume

121

pub_type

杂志文章

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Differential regulation of inhibin/activin alpha- and beta A-subunit and follistin mRNAs by cyclic AMP and phorbol ester in cultured human granulosa-luteal cells.