Testosterone production by mouse Leydig cells is stimulated in vitro by atrial natriuretic factor

Mukhopadhyay, Amal K.; Bohnet, H. G.; Leidenberger, Freimut A.

doi:10.1016/0014-5793(86)80659-7

Cited by 66 publications

(26 citation statements)

References 25 publications

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“…Our results indicated that digitoxin have the inhibitory effect on the testicular function both in vivo and in vitro. This effect may partly result from the increased secretion of atrial natriuretic peptide (ANP) from atrial myocytes, and ANP can exert a potent direct inhibitory effect on testicular function [Mukhopadhyay et al, 1986;Foresta et al, 1993]. In addition, this study showed that digitoxin can act directly on the testicular interstitial cells to inhibit the secretion of testosterone (Fig.…”

Section: Discussionmentioning

confidence: 81%

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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Section: Discussionmentioning

confidence: 81%

Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

Wang¹,

Lin²,

Hwang³

et al. 1999

J. Cell. Biochem.

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“…An early study suggested that long-term digoxin therapy may also depress LH secretion by the pituitary gland (Tappler & Katz, 1979), a phenomenon which would be expected to exacerbate the direct inhibitory actions of the drug on testicular testosterone secretion. Similarly, the digoxininduced blockade of testosterone synthesis in vivo may be reinforced by the concomitant fall of atrial natriuretic peptide (ANP), a peptide which stimulates testosterone secretion in vitro in a time and concentration-dependent manner (Mukhopadhyay et al, 1986;Foresta & Mioni, 1993).…”

Section: Discussionmentioning

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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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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“…A potential role for ANF in the maturation of the oocyte was previously suggested by the demonstration of ANF receptors in mammalian gonads [3,4,19] and the ability of these receptors to mediate ANF-induced increases in steroid production. The peptide stimulates testosterone production in mouse interstitial cells [20] and enhances both basal and gonadotropin-stimulated testosterone secretion from mouse Leydig cells [21]. ANF also enhances LH-induced progesterone secretion in cultured ovarian granulosa-lutein cells [22].…”

Section: Potentiation Of Oocyte Maturationmentioning

confidence: 97%

Atrial Natriuretic Factor Activates Cyclic Adenosine 3′,5′-Monophosphate Phosphodiesterase in Xenopus Laevis Oocytes and Potentiates Progesterone-Induced Maturation via Cyclic Guanosine 5′-Monophosphate Accumulation

Sandberg¹,

Bor²,

Ji³

et al. 1993

Biology of Reproduction

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Xenopus oocytes were found to express atrial natriuretic factor (ANF) receptors that activate guanylate cyclase and stimulate cyclic guanosine 5'-monophosphate (cGMP) production in a dose- and time-dependent manner. A truncated fragment of ANF, known to bind to mammalian ANF receptors without stimulating cGMP accumulation, did not elicit a cGMP response in oocytes. In addition, preincubation with ANF increased the number of oocytes that underwent progesterone-induced maturation. The maximally effective dose of ANF (1 microM) elevated intracellular and extracellular cGMP accumulation from 50 to 200 and 5 to 800 fmol/oocyte, respectively, and increased the number of maturing oocytes by up to 3-fold. ANF's effects on progesterone-induced maturation were mimicked by nonhydrolyzable analogues of cGMP. ANF and 8-Br-cGMP had no effect on maturation in the absence of progesterone, indicating that elevation of cGMP alone is not sufficient to induce maturation. Dibutyryl-cGMP was as effective as 8-Br-cGMP, whereas 8-Br-guanosine monophosphate, 8-Br-guanosine, and 8-Br-cyclic inosine monophosphate did not potentiate ovum maturation. In Xenopus oocytes, an initial step in progesterone-induced maturation is the reduction of intracellular cAMP levels; both ANF and 8-Br-cGMP lowered cAMP levels and enhanced progesterone's ability to do so. This decrease in cAMP levels was attributable to increased cAMP-phosphodiesterase activity, which was enhanced by both ANF and 8-Br-cGMP. These findings, and the presence of functional ANF receptors on Xenopus oocytes, demonstrate that ANF can participate in ovum development by stimulation of cGMP accumulation and activation of cAMP phosphodiesterase, thereby potentiating progesterone's ability to decrease cAMP levels and promote ovum maturation.

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Testosterone production by mouse Leydig cells is stimulated in vitro by atrial natriuretic factor

Cited by 66 publications

References 25 publications

Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

Inhibition of testosterone secretion by digitoxin 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

Atrial Natriuretic Factor Activates Cyclic Adenosine 3′,5′-Monophosphate Phosphodiesterase in Xenopus Laevis Oocytes and Potentiates Progesterone-Induced Maturation via Cyclic Guanosine 5′-Monophosphate Accumulation

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Testosterone production by mouse Leydig cells is stimulated in vitro by atrial natriuretic factor

Cited by 66 publications

References 25 publications

Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells

Inhibition of testosterone secretion by digitoxin 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

Atrial Natriuretic Factor Activates Cyclic Adenosine 3′,5′-Monophosphate Phosphodiesterase in Xenopus Laevis Oocytes and Potentiates Progesterone-Induced Maturation via Cyclic Guanosine 5′-Monophosphate Accumulation

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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