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Inhibition of protein synthesis and hormone-sensitive steroidogenesis in response to hydrogen peroxide in rat luteal cells.
- Source :
-
Endocrinology [Endocrinology] 1994 Feb; Vol. 134 (2), pp. 588-95. - Publication Year :
- 1994
-
Abstract
- Hydrogen peroxide (H2O2) is generated in the corpus luteum at functional luteal regression and produces rapid antigonadotropic effects in rat luteal cells. However, the mechanism by which peroxide interrupts LH- and cAMP-sensitive progesterone synthesis is unknown. The post-cAMP site of H2O2 action is due to the reduced cholesterol availability in mitochondria, and this process is well known to be dependent on protein synthesis. Therefore, we examined whether H2O2 may interfere with protein and RNA synthesis, and whether such responses may be associated with inhibition of steroidogenesis. Incorporation of radiolabeled amino acids into luteal proteins was inhibited in response to H2O2 in a time- and dose-dependent manner, and these doses are similar to those that inhibit progesterone synthesis, shown earlier in the identical paradigm. The inhibitory effect of H2O2 on amino acid incorporation was not due to increased protein degradation, impaired transport of amino acids, or depletion of cellular ATP levels. H2O2 also inhibited RNA synthesis, increased RNA degradation, and impaired the efficiency of mRNA as a translation template. The time course for the inhibitory effect of H2O2 on protein and RNA synthesis was very rapid and coincident with inhibition of steroidogenesis. Inhibition of protein and RNA synthesis and steroidogenesis were reversed by preincubation of cells with the cell-permeable metal chelator o-phenanthroline, which implicates metal-dependent radical generation as the probable mediator of these actions of H2O2. We conclude that the target of the post-cAMP site of peroxide-induced inhibition of cAMP-dependent steroidogenesis is the inhibition of rapidly inducible proteins that are known to mediate translocation of cholesterol within mitochondria, where it is used as a substrate for pregnenolone synthesis.
- Subjects :
- Amino Acids metabolism
Animals
Benzamides pharmacology
Carbon Radioisotopes
Corpus Luteum drug effects
Dose-Response Relationship, Drug
Female
Hydroxycholesterols pharmacology
In Vitro Techniques
Kinetics
Luteinizing Hormone pharmacology
Phenanthrolines pharmacology
RNA, Messenger biosynthesis
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Uridine metabolism
Corpus Luteum metabolism
Cycloheximide pharmacology
Dactinomycin pharmacology
Hydrogen Peroxide pharmacology
Progesterone biosynthesis
Protein Biosynthesis drug effects
RNA biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 134
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 7507829
- Full Text :
- https://doi.org/10.1210/endo.134.2.7507829