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Inhibitory effects of gossypol on adrenal function
Y W Wu1, C L Chik, B D Albertson
1Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Maryland.
Acta Endocrinologica
|June 1, 1991
Summary
Gossypol affects adrenal gland function by altering cell membrane properties and inhibiting key steroidogenic enzymes. This impacts hormone production and responses to stimulation.
Area of Science:
- Endocrinology
- Cell Biology
- Pharmacology
Background:
- Gossypol is known as an antifertility agent.
- It exhibits inhibitory actions on various membrane-associated enzymes.
- This suggests a potential generalized effect on cell membranes.
Purpose of the Study:
- To investigate the hypothesis that gossypol has a generalized effect on cell membranes.
- To examine the impact of gossypol on human and rat adrenal gland function.
- To determine gossypol's effects on membrane microviscosity, steroidogenic enzymes, and hormonal responses.
Main Methods:
- Assessed membrane microviscosity using fluorescence polarization in human adrenal microsomal- and mitochondrial-enriched membranes.
- Measured the activity of three adrenal steroidogenic enzymes: 3 beta-hydroxysteroid dehydrogenase delta 5-delta 4 isomerase, 11-hydroxylase, and 21-hydroxylase.
- Evaluated cAMP and cortisol responses to ACTH in intact human adrenocortical cells and in vivo corticosterone response to ACTH in rats.
Main Results:
- Gossypol increased membrane microviscosity in a dose-dependent manner.
- Inhibition of 3 beta-hydroxysteroid dehydrogenase delta 5-delta 4 isomerase and 11-hydroxylase was observed, while 21-hydroxylase remained unaffected.
- High doses of gossypol inhibited ACTH-stimulated cAMP and cortisol levels in human cells, and reduced corticosterone response in rats.
Conclusions:
- Gossypol exerts multiple effects on adrenal function.
- These effects likely stem from a generalized impact on cell membranes, influencing microviscosity and steroidogenesis.
- Gossypol's actions on adrenal steroidogenesis and hormonal responses suggest a broad mechanism of action.
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