The role of cyclic AMP production, calcium channel activation and enzyme activities in the inhibition of testosterone secretion by amphetamine

Tsai, Shau‐Wei; Chen, Jiann Jong; Chiao, Yu Chung; Lu, Chien Chen; H, Lin; Yeh, Jiun Yih; Lo, Ming Jae; Kau, Mei Mei; Wang, Shyi Wu; Wang, Paulus S.

doi:10.1038/sj.bjp.0701463

Cited by 32 publications

(37 citation statements)

References 44 publications

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“…It is well established that hCG stimulates the secretion of testosterone both in vivo (Saez & Forest, 1979;Padron et al, 1980;Wang et al, 1994;Tsai et al, 1996a) and in vitro (Simpson et al, 1987;Nakhla et al, 1989;Wang et al, 1994;Tsai et al, 1996a;1997) via mechanisms involving increased production of cyclic AMP (Avallet et al, 1987;Petersson et al, 1988;Sakai et al, 1989;Wang et al, 1994, Tsai et al, 1996a. In accord with these data we observed a marked increase in the cyclic AMP content of cells exposed to hCG.…”

Section: Discussionsupporting

confidence: 81%

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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

H¹,

Wang

Tsai³

et al. 1998

British J Pharmacology

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1 In vivo and in vitro experiments were performed to examine inhibitory e ects of digoxin on testosterone secretion and to determine possible underlying mechanisms. 2 A single intravenous injection of digoxin (1 mg kg 71 ) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats. 3 Digoxin (10 77 ± 10 74 M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro. 4 Digoxin (10 77 ± 10 74 M) also diminished the basal and hCG-stimulated production of cyclic 3' : 5'-adenosine monophosphate (AMP) and attenuated the stimulatory e ects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells. 5 Digoxin (10 74 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 in¯uence 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 .

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Section: Discussionsupporting

confidence: 81%

“…The method of collagenase dispersion of testicular interstitial cells followed the procedure described by Tsai et al, (1997). Five decapsulated testes were added to a 50 ml polypropylene tube containing 5 ml preincubation medium and 700 mg collagenase (Type IA, Sigma, U.S.A.).…”

Section: Preparation Of Testicular Interstitial Cellsmentioning

confidence: 99%

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

H¹,

Wang

Tsai³

et al. 1998

British J Pharmacology

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“…The method used for the collagenase dispersion of TICs has been described elsewhere [Tsai et al, 1997]. Briefly, the medium (1% bovine serum albumin in Hank's balanced salt solution, with HEPES 25 mM, sodium bicarbonate 0.35 g/L, penicillin-G 100 IU/ml, streptomycin sulfate 50 mg/ml, heparin 2550 USP K U/L, pH 7.3) was aerated and saturated with 95% O 2 and 5% CO 2 before use.…”

Section: Preparation Of Ticsmentioning

confidence: 99%

Role of testicular interstitial macrophages in regulating testosterone release in hyperprolactinemia

Huang¹,

Yeh²,

Kan³

et al. 2002

J of Cellular Biochemistry

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Hyperprolactinemia-induced hypogonadism has been linked to a dysfunction of the hypothalamus-pituitary-testis axis. The direct inhibitory effects of prolactin on the testicular release of testosterone have also been demonstrated, though their mechanisms remain unclear. Incubation of rat testicular interstitial cells (TICs) with prolactin stimulated the release of testosterone. TICs from rats with anterior pituitary-grafting-induced hyperprolactinemia release lower amounts of testosterone than controls. However, Leydig cells isolated from anterior pituitary-grafted rats release a greater amount of testosterone. These paradoxical observations have remained unexplained. This study examined the roles of testicular interstitial macrophages and of their product, tumor necrosis factor-alpha (TNF-alpha), in regulating Leydig cells under condition of hyperprolactinemia. Hyperprolactinemia was induced by grafting two anterior pituitary glands of rats under the renal capsule. Control animals were grafted with rat cortex tissue. The rats were sacrificed 6 weeks later. TICs and macrophages, and Leydig cells were isolated for in vitro incubation and drugs challenge. Testosterone released by testicular interstitial or Leydig cells was measured by radioimmunoassay. TNF-alpha concentration in the medium of TICs or macrophages was measured by enzyme-linked immunosorbent assay (ELISA). A dose-dependent stimulation of TNF-alpha secretion in the medium of TICs or macrophages by the prolactin challenge was observed. Higher amounts of TNF-alpha were released by TICs in the anterior pituitary-grafted rats than in the control group. In contrast, the release of TNF-alpha by testicular interstitial macrophages isolated from the anterior pituitary- and cortex-grafted groups was quantitatively similar. Challenge with human chorionic gonadotropin did not modify the TNF-alpha release by testicular interstitial macrophages in either group. Challenge of Leydig cells with TNF-alpha inhibited their release of testosterone stimulated by human chorionic gonadotropin, but not their basal testosterone release. These different patterns of testosterone release in TICs versus Leydig cells cultures in anterior pituitary-grafted rats may be due to the influence of testicular interstitial macrophages. These observations correlate with in vivo conditions, where prolactin increases the release of TNF-alpha by testicular interstitial macrophages, which, in turn, decreases the human chorionic gonadotropin-stimulated release of testosterone by Leydig cells. In summary, hyperprolactinemia-induced hypogonadism involves a mechanism of prolactin-originated, macrophage-mediated inhibitory regulation of testosterone release by Leydig cells. TNF-alpha, one of the cytokines secreted by macrophages, may play a key role in this mechanism.

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“…The method of collagenase dispersion of testicular interstitial cells followed the procedure described by Tsai et al [1997]. Generally, each group contained cells from eight dispersions (n ϭ 8).…”

Section: Preparation Of Testicular Interstitial Cellsmentioning

confidence: 99%

Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

Wang¹,

Lin²,

Hwang³

et al. 1999

J. Cell. Biochem.

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Both in vivo and in vitro experiments were conducted to determined the effects of digitoxin on the secretion of testosterone, and its underlying mechanisms including testicular adenosine 3':5'-cyclic monophosphate (cAMP), and the activities of steroidogenic enzymes. Male rats were injected with digitoxin, human chorionic gonadotropin (hCG), or hCG plus digitoxin via a jugular catheter. Blood samples were collected immediately before and at 30 and 60 min after the challenge, and analyzed for testosterone by radioimmunoassay. In an in vitro study, rat testicular interstitial cells were isolated and incubated with digitoxin, hCG, 8-bromo-cAMP (8-Br-cAMP), digitoxin plus hCG, or digitoxin plus 8-Br-cAMP at 34 degrees C for 1 h. The media were collected and analyzed for testosterone. For studying cAMP accumulation, testicular interstitial cells were incubated for 1 h in the medium containing isobutyl-1-methylxanthine (IBMX) and different doses of digitoxin with the absence or presence of hCG. After incubation, cells were processed for determining cAMP content. Intravenous injection of digitoxin decreased hCG-stimulated, but not basal, plasma testosterone levels. Administration of digitoxin in vitro resulted in an inhibition of both basal and hCG- as well as 8-Br-cAMP-stimulated release of testosterone. In addition, digitoxin diminished hCG-stimulated cAMP accumulation in rat testicular interstitial cells. Furthermore, digitoxin inhibited the activity of cytochrome P450 side chain cleavage enzyme (P450scc) but failed to affect the activities of other steroidogenic enzymes. Taken together, these results suggest that the acute inhibitory effect of digitoxin on the testosterone production in testicular interstitial cells involves, at least partly, an inefficiency of post-cAMP events, and a decrease of P450scc activity.

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The role of cyclic AMP production, calcium channel activation and enzyme activities in the inhibition of testosterone secretion by amphetamine

Cited by 32 publications

References 44 publications

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

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

Role of testicular interstitial macrophages in regulating testosterone release in hyperprolactinemia

Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

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The role of cyclic AMP production, calcium channel activation and enzyme activities in the inhibition of testosterone secretion by amphetamine

Cited by 32 publications

References 44 publications

Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells

Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells

Role of testicular interstitial macrophages in regulating testosterone release in hyperprolactinemia

Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

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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

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