The involvement of nitric oxide in stress-impaired testicular steroidogenesis

Kostic, Tatjana S.; Andrić, Silvana A.; Kovačević, Radmila; Marić, D.

doi:10.1016/s0014-2999(98)00057-0

Cited by 51 publications

(35 citation statements)

References 31 publications

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“…Intratesticular injection of this non-selective NOS inhibitor partially antagonized the increase in intratesticular nitrite levels, and normalized in vitro hCGstimulated testosterone in stressed animals (Kostic et al 1998b). This inhibitor added in vitro also increased basal and hCG-stimulated testosterone production in unstressed animals (Welch et al 1995).…”

Section: Discussionmentioning

confidence: 89%

“…The stress-induced decrease in serum androgens is accompanied by significant changes in the activities of two steroidogenic enzymes, 3 -hydroxysteroid dehydrogenase (3 HSD) and 17 -hydroxylase/C17-20 lyase (P450c17) (Srivastava et al 1993, Akinbami et al 1994, Maric et al 1996, Kostic et al 1997, 1998a. In vitro androgenesis by decapsulated testes from stressed rats exposed to human chorionic gonadotropin (hCG) for 3 h is also reduced, and this reduction coincides with an elevation in the testicular nitrite levels, a stable oxidation product of the nitric oxide pathway (Kostic et al 1998b). …”

Section: Introductionmentioning

confidence: 99%

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Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis

Kostic¹,

Andrić²,

Marić³

et al. 1999

Journal of Endocrinology

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The immobilization stress induces an acute inhibition of testicular steroidogenesis that is mediated by the nitric oxide (NO) signaling pathway. Here we compared the effects of 2-h immobilization stress on in vivo and in vitro rat steroidogenesis at two time points, 0 h and 6 h after the end of the stress session. As expected, serum androgens and human chorionic gonadotropin (hCG)-stimulated progesterone and testosterone production by testicular tissue were inhibited at 0 h, and also at the 6-h time point. Both the acute and sustained inhibitions of in vitro steroidogenesis were accompanied by a significant increase in nitrite, a stable oxidation product of NO. To clarify which subtype of NO synthase (NOS) (constitutive (cNOS) or inducible (iNOS)) participates in down-regulation of testicular steroidogenesis, aminoguanidine hydrochloride (AG), a selective iNOS inhibitor, was employed. Intratesticular injection of AG prevented the sustained, but not the acute, stress-induced decrease in serum testosterone.When added in vitro, it also prevented the sustained decrease in steroid production and increase in nitrite production by testicular tissue, both in a dose-dependent manner and with EC 50 of about 50 µM. Furthermore, AG added in vivo and in vitro effectively blocked the sustained decrease in 3 -hydroxysteroid dehydrogenase (3 HSD) and 17 -hydroxylase/C17-20 lyase (P450c17) activities. In all concentrations employed, AG did not affect serum androgens and in vitro steroid and nitrite production in unstressed animals. These results indicate that the NO signaling pathway participates in acute and sustained stress-induced down-regulation of testicular steroidogenesis, presumably through its direct action on 3 HSD and P450c17. The acute NO production is controlled by cNOS and the sustained production of this messenger is controlled by iNOS.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis

Kostic¹,

Andrić²,

Marić³

et al. 1999

Journal of Endocrinology

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“…58,59 Pharmacological inhibition of endogenous NO in cultured Leydig cells increases both basal and gonadotropinstimulated testosterone production. 60,61 It is believed that NO inhibits the synthesis and release of testosterone from Leydig cells through the inhibition of steroidogenic enzymes, most likely P 450 scc, in a cGMP-independent manner. 6,62 Our current work adds newer perspective to the concept that NO derived from nNOS expressed in Leydig cells may be acting in an autocrine manner to regulate Leydig cell function.…”

Section: Discussionmentioning

confidence: 99%

An Alternative Promoter of the Human Neuronal Nitric Oxide Synthase Gene Is Expressed Specifically in Leydig Cells

Wang¹,

Newton²,

Miller³

et al. 2002

The American Journal of Pathology

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Neuronal nitric oxide synthase (nNOS) plays a modulatory role in the biology of a variety of neuroendocrine tissues and is especially relevant to gonadal function. We have previously reported the cloning and characterization of a variant of the nNOS protein, termed testis nNOS (TnNOS), the mRNA for which was restricted in expression to male gonadal tissues. To examine the cell-specificity of the testis-specific NOS regulatory regions we defined patterns of ␤-galactosidase expression of an insertional transgene in which the reporter gene lacZ was under the transcriptional control of the human TnNOS promoter. ␤-galactosidase activity was detected exclusively in the interstitial cells of the testis in transgenic mice. These cells also evidenced positive staining for nNOS protein and were identified as androgen-producing Leydig cells by staining with the Leydig cell marker, P 450 scc. Expression of the promoter was absent in cells of the seminiferous tubules, specifically germline cells of different stages and Sertoli cells. In contrast to the male gonad, ␤-galactosidase activity was not detected in ovaries of adult female mice. Activity was also not evident in organs known to express full-length nNOS, such as skeletal muscle, kidney, or cerebellum. The same pattern of ␤-galactosidase staining was observed in independent transgenic founders and was distinct from that observed for an endothelial NOS promoter/reporter transgene. In the testis of male adult eNOS promoter-reporter transgenic mice, ␤-galactosidase activity was expressed only in endothelial cells of large-and medium-sized arterial blood vessels. Transcriptional activity of the Of the three known human nitric oxide synthases (NOS) isoforms, the neuronal nitric oxide synthase (nNOS) has unique properties. The nNOS (NOS1) isoform is expressed from a very complex human genomic locus spanning 240 kb at 12q24.2.

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“…On the contrary, high levels of NO were associated with testosterone inhibition with no change in cGMP production. Additional studies found that immobilization stress increased NO in rat testis with a concomitant reduction in testosterone production (Kostic et al 1998) and that injection of an NO donor into the testis mimicked this effect (Kostic et al 2000). Furthermore, inhibiting NOS increased testosterone production in Leydig cells (Dobashi et al 2001).…”

Section: No and Steroidogenesismentioning

confidence: 95%

eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia

Ducsay¹,

Myers²

2011

Journal of Endocrinology

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Nitric oxide (NO) plays a role in a wide range of physiological processes. Aside from its widely studied function in the regulation of vascular function, NO has been shown to impact steroidogenesis in a number of different tissues. The goal of this review is to explore the effects of NO on steroid production and further, to discern its source(s) and mechanism of action. Attention will be given to the regulation of NO synthases in specific endocrine tissues including ovaries, testes, and adrenal glands. The effects of hypoxia on generation of NO and subsequent effects on steroid biosynthesis will also be examined. Finally, a potential model for the interaction of hypoxia on NO synthesis and steroid production is proposed.

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The involvement of nitric oxide in stress-impaired testicular steroidogenesis

Cited by 51 publications

References 31 publications

Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis

Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis

An Alternative Promoter of the Human Neuronal Nitric Oxide Synthase Gene Is Expressed Specifically in Leydig Cells

eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia

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