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Trifluoperazine inhibits progesterone and cyclic AMP production in granulosa cells of the hen (Gallus domesticus).

Authors
  • Asem, E K
  • Hertelendy, F
Type
Published Article
Journal
General and comparative endocrinology
Publication Date
Oct 01, 1986
Volume
64
Issue
1
Pages
107–111
Identifiers
PMID: 3030874
Source
Medline
License
Unknown

Abstract

Unstimulated (basal) as well as luteinizing hormone (LH)-promoted progesterone production in collagenase-dispersed hen granulosa cells was inhibited in a dose-related manner by two phenothiazines, trifluoperazine (TFP) and chlorpromazine (CP), both of which are known calmodulin antagonists. Using TFP, the more potent antagonist of the two, it was found that LH-stimulated cyclic AMP production was also suppressed. Moreover, TFP attenuated the steroidogenic effects of both 8-bromo-cyclic AMP and isobutylmethylxanthine but had no effect on the conversion of pregnenolone to progesterone. The inhibitory effects of TFP on steroidogenesis were reversible. It is concluded that phenothiazines inhibit steroidogenesis in ovarian granulosa cells by acting at multiple sites both proximal and distal to cyclic AMP generation without influencing the enzyme complex responsible for the conversion of pregnenolone to progesterone. The results are discussed in relation to calmodulin- and non-calmodulin-mediated actions of phenothiazines.

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