Effect of a Dopamine Agoniston Luteinizing Hormone Receptors, Cyclic AMP Production and Steroidogenesis in Rat Leydig Cells

Dirami, Ghenima; Cooke, Brian A.

doi:10.1006/taap.1998.8429

Cited by 12 publications

(11 citation statements)

References 51 publications

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“…In vitro studies with Leydig cells from animals treated in vivo with mesulergine revealed a significant decrease of human [ 125 I]chorionic gonadotropin (hCG) binding to the Leydig cells. This effect was observed with cells from rats treated with mesulergine for only 1 week; and was more pronounced in cells from animals treated for 5 weeks (21). This effect was not due to a decrease in LH/hCG receptor affinity but due to a decrease in the number of receptors.…”

Section: Toxicologymentioning

confidence: 77%

“…As with many other compounds (calcium channel blockers, ammonium perfluoroctanoate, oxolinic acid, flutamide, cimetidine) dopamine agonists have been shown to induce Leydig cell hyperplasia and adenomas, when given chronically to rats (20,21,80). A sustained increase of luteinizing hormone (LH) levels is a common property that causes this effect.…”

Section: Toxicologymentioning

confidence: 99%

“…Rats receiving mesulergine for 1-2 years develop Leydig cell tumors, mostly adenomas. The underlying mechanism appears to be a rise in circulating LH levels that is preceded by short-term decrease in the secretion of LH (21,80,81). After approximately 5 weeks of treatment, mesulergine causes hypertrophy of Leydig cells that is followed by hyperplasia and, after 1 to 2 years of treatment, by Leydig cell adenomas (20).…”

Section: Toxicologymentioning

confidence: 99%

“…Glucocorticoids are also known to reduce LH receptors in rats in vivo (80,81). In Leydig cells of rats treated for 5 weeks with mesulergine, the production of testosterone as well as that of cAMP is decreased (21). Testosterone but not pregnenolone production remains decreased even after the addition of the cell permeant 22-R-hydroxycholesterol to Leydig cells, CNS Drug Reviews, Vol.…”

Section: Toxicologymentioning

confidence: 99%

See 3 more Smart Citations

Mesulergine: A Review

Galanopoulou

Giannakopoulos

1999

CNS Drug Reviews

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Section: Toxicologymentioning

confidence: 77%

Section: Toxicologymentioning

confidence: 99%

Section: Toxicologymentioning

confidence: 99%

Section: Toxicologymentioning

confidence: 99%

See 2 more Smart Citations

Mesulergine: A Review

Galanopoulou

Giannakopoulos

1999

CNS Drug Reviews

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“…An increased expression of the cytochrome P450 side chain cleavage (P450scc) enzyme (Lahav et al, 1996;Lauber et al, 1993), and 3b-hydroxysteroid dehydrogenase (3b-HSD) (GonzaÂ lezbeen demonstrated. The conversion of cholesterol to pregnenolone is the rate-limiting step in the ®nal formation of progesterone and this step is regulated by mitochondrial enzyme P450scc (Dirami & Cooke, 1998;Too et al, 1984;Waterman & Simpson, 1985). The steroidogenic acute regulatory (StAR) protein is thought to facilitate cholesterol transfer through the mitochondria membrane, making it available to P450scc (Reinhart et al, 1999), and it is believed to be the key regulator of the biosynthesis of steroid hormones.…”

Section: Introductionmentioning

confidence: 99%

Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells

Chen

Wang²,

Chien³

et al. 2001

British J Pharmacology

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1 Digoxin (10 77 ± 10 75 M) or digitoxin (10 77 ± 10 75 M) decreased the basal and human chorionic gonadotropin (hCG)-stimulated release of progesterone from rat granulosa cells. 2 Digoxin (10 75 M) or digitoxin (10 75 M) attenuated the stimulatory eects of forskolin and 8-bromo-cyclic 3' : 5'-adenosine monophosphate (8-Br-cAMP) on progesterone release from rat granulosa cells. 3 Digoxin (10 75 M) or digitoxin (10 75 M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450 scc ) activity (conversion of 25-hydroxyl cholesterol to pregnenolone) in rat granulosa cells but did not in¯uence the activity of 3b-hydroxysteroid dehydrogenase (3b-HSD). 4 Neither progesterone production nor P450scc activity in rat granulosa cells was altered by the administration of ouabain. 5 Digoxin (10 75 M) or digitoxin (10 75 M), but not ouabain, decreased the expression of P450scc and steroidogenic acute regulatory (StAR) protein in rat granulosa cells. 6 The present results suggest that digoxin and digitoxin decrease the progesterone release by granulosa cells via a Na + ,K + -ATPase-independent mechanism involving the inhibition of post-cyclic AMP pathway, cytochrome P450scc and StAR protein functions.

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Progesterone attenuates the inhibitory effects of cardiotonic digitalis on pregnenolone production in rat luteal cells

Chen¹,

Chien²,

Wang³

2002

J of Cellular Biochemistry

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Previous studies have shown that digoxin decreases testosterone secretion in testicular interstitial cells. However, the effect of digoxin on progesterone secretion in luteal cells is unclear. Progesterone is known as an endogenous digoxin-like hormone (EDLH). This study investigates how digitalis affected progesterone production and whether progesterone antagonized the effects of digitalis. Digoxin or digitoxin, but not ouabain, decreased the basal and human chorionic gonadotropin (hCG)-stimulated progesterone secretion as well as the activity of cytochrome P450 side chain cleavage enzyme (P450scc) in luteal cells. 8-Br-cAMP and forskolin did not affect the reduction. Neither the amount of P450scc, the amount of steroidogenic acute regulatory (StAR) protein, nor the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) was affected by digoxin or digitoxin. Moreover, in testicular interstitial and luteal cells, progesterone partially attenuated the reduction of pregnenolone by digoxin or digitoxin and the progesterone antagonist, RU486, blocked this attenuation. These new findings indicated that (1) digoxin or digitoxin inhibited pregnenolone production by decreasing the activity of P450scc enzyme, but not Na(+)-K(+)-ATPase, resulting in a decrease on progesterone secretion in rat luteal cells, and (2) the inhibitory effect on pregnenolone production by digoxin or digitoxin was reversed partially by progesterone. In conclusion, digoxin or digitoxin decreased progesterone production via the inhibition of pregnenolone by decreasing P450scc activity. Progesterone, an EDLH, could antagonize the effects of digoxin or digitoxin in luteal cells.

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Effect of a Dopamine Agoniston Luteinizing Hormone Receptors, Cyclic AMP Production and Steroidogenesis in Rat Leydig Cells

Cited by 12 publications

References 51 publications

Mesulergine: A Review

Mesulergine: A Review

Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells

Progesterone attenuates the inhibitory effects of cardiotonic digitalis on pregnenolone production in rat luteal cells

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