Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450(scc) activity in rat testicular interstitial cells

Ho Lin, Shyi Wu Wang, Shiow Chwen Tsai, Jiann Jong Chen, Yu Chung Chiao, Chien Chen Lu, William Ji Sien Huang, Guei Jane Wang, Chieh Fu Chen, Paulus S. Wang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

1. In vivo and in vitro experiments were performed to examine inhibitory effects of digoxin on testosterone secretion and to determine possible underlying mechanisms. 2. A single intravenous injection of digoxin (1 μg kg-1) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats. 3. Digoxin (10-7-10-4 M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro. 4. Digoxin (10-7-10-4 M) also diminished the basal and hCG-stimulated production of cyclic 3':5'-adenosine monophosphate (AMP) and attenuated the stimulatory effects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells. 5. Digoxin (10-4 M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450(scc) activity (conversion of 25-hydroxy cholesterol to pregnenolone) in the testicular interstitial cells but did not influence the activity of other steroidogenic enzymes. 6. These results suggest that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450(scc).

Original languageEnglish (US)
Pages (from-to)1635-1640
Number of pages6
JournalBritish Journal of Pharmacology
Volume125
Issue number8
DOIs
StatePublished - 1998

Fingerprint

Leydig Cells
Digoxin
Cyclic AMP
Cytochrome P-450 Enzyme System
Testosterone
Chorionic Gonadotropin
Pregnenolone
Colforsin
Enzymes
Adenosine Monophosphate
Adenylyl Cyclases
Intravenous Injections
Cholesterol

Keywords

  • Adenylyl cyclase
  • Cyclic AMP
  • Cytochrome P450(scc)
  • Digoxin
  • Testicular interstitial cells
  • Testosterone

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450(scc) activity in rat testicular interstitial cells. / Lin, Ho; Wang, Shyi Wu; Tsai, Shiow Chwen; Chen, Jiann Jong; Chiao, Yu Chung; Lu, Chien Chen; Huang, William Ji Sien; Wang, Guei Jane; Chen, Chieh Fu; Wang, Paulus S.

In: British Journal of Pharmacology, Vol. 125, No. 8, 1998, p. 1635-1640.

Research output: Contribution to journalArticle

Lin, Ho ; Wang, Shyi Wu ; Tsai, Shiow Chwen ; Chen, Jiann Jong ; Chiao, Yu Chung ; Lu, Chien Chen ; Huang, William Ji Sien ; Wang, Guei Jane ; Chen, Chieh Fu ; Wang, Paulus S. / Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450(scc) activity in rat testicular interstitial cells. In: British Journal of Pharmacology. 1998 ; Vol. 125, No. 8. pp. 1635-1640.
@article{ddd4a36bc55349ef84e5a192b200ff2a,
title = "Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450(scc) activity in rat testicular interstitial cells",
abstract = "1. In vivo and in vitro experiments were performed to examine inhibitory effects of digoxin on testosterone secretion and to determine possible underlying mechanisms. 2. A single intravenous injection of digoxin (1 μg kg-1) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats. 3. Digoxin (10-7-10-4 M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro. 4. Digoxin (10-7-10-4 M) also diminished the basal and hCG-stimulated production of cyclic 3':5'-adenosine monophosphate (AMP) and attenuated the stimulatory effects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells. 5. Digoxin (10-4 M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450(scc) activity (conversion of 25-hydroxy cholesterol to pregnenolone) in the testicular interstitial cells but did not influence the activity of other steroidogenic enzymes. 6. These results suggest that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450(scc).",
keywords = "Adenylyl cyclase, Cyclic AMP, Cytochrome P450(scc), Digoxin, Testicular interstitial cells, Testosterone",
author = "Ho Lin and Wang, {Shyi Wu} and Tsai, {Shiow Chwen} and Chen, {Jiann Jong} and Chiao, {Yu Chung} and Lu, {Chien Chen} and Huang, {William Ji Sien} and Wang, {Guei Jane} and Chen, {Chieh Fu} and Wang, {Paulus S.}",
year = "1998",
doi = "10.1038/sj.bjp.0702229",
language = "English (US)",
volume = "125",
pages = "1635--1640",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450(scc) activity in rat testicular interstitial cells

AU - Lin, Ho

AU - Wang, Shyi Wu

AU - Tsai, Shiow Chwen

AU - Chen, Jiann Jong

AU - Chiao, Yu Chung

AU - Lu, Chien Chen

AU - Huang, William Ji Sien

AU - Wang, Guei Jane

AU - Chen, Chieh Fu

AU - Wang, Paulus S.

PY - 1998

Y1 - 1998

N2 - 1. In vivo and in vitro experiments were performed to examine inhibitory effects of digoxin on testosterone secretion and to determine possible underlying mechanisms. 2. A single intravenous injection of digoxin (1 μg kg-1) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats. 3. Digoxin (10-7-10-4 M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro. 4. Digoxin (10-7-10-4 M) also diminished the basal and hCG-stimulated production of cyclic 3':5'-adenosine monophosphate (AMP) and attenuated the stimulatory effects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells. 5. Digoxin (10-4 M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450(scc) activity (conversion of 25-hydroxy cholesterol to pregnenolone) in the testicular interstitial cells but did not influence the activity of other steroidogenic enzymes. 6. These results suggest that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450(scc).

AB - 1. In vivo and in vitro experiments were performed to examine inhibitory effects of digoxin on testosterone secretion and to determine possible underlying mechanisms. 2. A single intravenous injection of digoxin (1 μg kg-1) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats. 3. Digoxin (10-7-10-4 M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro. 4. Digoxin (10-7-10-4 M) also diminished the basal and hCG-stimulated production of cyclic 3':5'-adenosine monophosphate (AMP) and attenuated the stimulatory effects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells. 5. Digoxin (10-4 M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450(scc) activity (conversion of 25-hydroxy cholesterol to pregnenolone) in the testicular interstitial cells but did not influence the activity of other steroidogenic enzymes. 6. These results suggest that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450(scc).

KW - Adenylyl cyclase

KW - Cyclic AMP

KW - Cytochrome P450(scc)

KW - Digoxin

KW - Testicular interstitial cells

KW - Testosterone

UR - http://www.scopus.com/inward/record.url?scp=0032406528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032406528&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0702229

DO - 10.1038/sj.bjp.0702229

M3 - Article

VL - 125

SP - 1635

EP - 1640

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 8

ER -