Nitric oxide control of steroidogenesis: Endocrine effects of NG-nitro-L-arginine and comparisons to alcohol

doi:10.1016/0024-3205(92)90384-2

Life Sciences

Volume 50, Issue 6, 1992, Pages PL35-PL40

https://doi.org/10.1016/0024-3205(92)90384-2 Get rights and content

Abstract

Recent studies suggest that nitric oxide (NO) may regulate hormone biosynthesis and secretion. This was tested by treating male rats with N^G-nitro-L-arginine methyl ester (NAME), a NO synthase inhibitor, and measuring serum and testicular interstitial fluid testosterone and serum corticosterone, luteinizing hormone (LH), and prolactin (PRL). The effect of N^G-nitro-L-arginine (NA), a less-soluble form of the same NO synthase inhibitor, on the reproductive suppressant actions of alcohol was also examined. NAME increased testosterone and corticosterone secretion dose-dependently without affecting LH and PRL secretion. The alcohol-induced suppression of testosterone or LH secretion was not altered by treatment with NA. Although effects of NAME and NA on other systems may be involved, these results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenos NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol.

References (20)

S.H. Snyder et al.
TIPS
(1991)
M.R. Waterman et al.
Mol. Cell. Endocrinol.
(1985)
P.F. Hall et al.
J. Biol. Chem.
(1975)
S. Moncada et al.
TIPS
(1991)
D.E. Johnston et al.
Biochem. Pharmacol.
(1981)
S. Moncada et al.
Pharmacol. Rev.
(1991)
D.S. Bredt et al.
Nature
(1991)
D.S. Bredt et al.
Nature
(1990)
P.K. Moore et al.
Br. J. Pharmacol.
(1990)
L.J. Ignarro
FASEB J.
(1989)

There are more references available in the full text version of this article.

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Tangeretin ameliorates erectile and testicular dysfunction in a rat model of hypertension
2020, Reproductive Toxicology
Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT₁R) and gp91^phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT₁R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT₁R/gp91^phox expressions and testicular eNOS and StAR expression.
Pro-steroidogenic and pro-spermatogenic actions of nitric oxide (NO) on the catfish, Clarias batrachus: An in vivo study
2017, General and Comparative Endocrinology
Citation Excerpt :
It is now established that NO acts as an important modulator of steroid secretion; however, reports are contradictory and equivocal. Adams et al. (1992, 1994) have shown that treatment of rat with NOS inhibitors like nitro-l-arginine, N-monomethyl-l-arginine (MMA) or l-NAME increases the circulating and testicular testosterone. On the contrary, treatments with NO donors such as isosorbide dinitrite (ISDN) or SNP or the NOS substrates l-arginine or l-arginine methyl ester (l-AME) or S-nitrosoglutathione (GSNO) resulted in significant decline in testosterone production in rats (Welch et al., 1995; Weissman et al., 2005), suggesting NO-induced inhibition of testosterone production.
In an earlier study we have demonstrated reproductive-stage dependent, cell specific existence of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS)/NO system in testis of the catfish, Clarias batrachus. The present study is an extension to examine the role of NO in steroidogenesis and spermatogenesis through in vivo administration of a NO donor, sodium nitroprusside (SNP) and a NOS inhibitor, N-nitro-l-arginine methyl ester (l-NAME) during the quiescence and recrudescence phase of the reproductive cycle of the catfish. Effects of these chemicals were assessed on the gonadosomatic index (GSI), levels of circulating & testicular testosterone, NO, activities of 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) in testis, expression of different NOS isoforms and testicular morphology in relation to spermatogenesis. SNP treatment increased the GSI, testicular and circulating testosterone & NO, activities of testicular 3β-HSD & 17β-HSD, and expression of NOS isoforms. It also increased the area and perimeters of interstitium and seminiferous tubules in the testis. It accelerated the spermatogenesis, as was evident from the large number of spermatids/spermatozoa in seminiferous tubules and very few spermatogonial cells/primary spermatocytes in comparison to the control testis. On the contrary, l-NAME significantly suppressed GSI, testosterone & NO levels in serum and testis, and activities of testicular 3β-HSD & 17β-HSD. It also suppressed the expression of NOSs in testis. Though l-NAME did not alter the spermatogonial mitotic proliferation with the advancement of testicular recrudescence, it halted the progression of spermatogenesis (meiotic division and spermatozoa formation) as was clear from the increase in spermatogonial cells and very few advanced germ cells in the seminiferous tubules in l-NAME treated testis, compared to the control testis. The above noted effects were highly pronounced in the recrudescing catfish. Their effects were very marginal and at a particular dose levels of SNP and l-NAME in the quiescent testis. This study distinctly provides evidence of pro-steroidogenic and pro-spermatogenic role of NO. This study also demonstrates the existence of eNOS in fish testis for the first time. The positive feedback control of expression of all isoform of NOS in testis by NO is also noteworthy.
Dietary supplementation of ginger and turmeric improves reproductive function in hypertensive male rats
2015, Toxicology Reports
Citation Excerpt :
NO can act as a free radical scavenger, inactivating and even inhibiting production of superoxide anions [10,46,24] which cause lipid peroxidation, a process which leads to functional impairment of spermatozoa [39]. This suggest a beneficial role for NO in the male reproductive system [2]. The inhibition of NO synthesis (by L-NAME administration), can result in a very low concentration of NO-mediated vasodilatation, an increase in vasoconstriction, and subsequently an increase in systemic vascular resistance, which contributes to BP elevation and its complications [19].
Ginger [Zingiber officinale Roscoe (Zingiberaceae)] and turmeric [Curcuma longa Linn (Zingiberaceae)] rhizomes have been reportedly used in folk medicine for the treatment of hypertension. However, the prevention of its complication such as male infertility remains unexplored. Hence, the aim of the present study was to investigate the preventive effects of ginger and turmeric rhizomes on some biomarkers of male reproductive function in L-NAME-induced hypertensive rats. Male Wistar rats were divided into seven groups (n = 10): normotensive control rats; induced (L-NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of L-NAME (40 mg/kg/day). The results revealed significant decrease in serum total testosterone and epididymal sperm progressive motility without affecting sperm viability in hypertensive rats. Moreover, increased oxidative stress in the testes and epididymides of hypertensive rats was evidenced by significant decrease in total and non-protein thiol levels, glutathione S-transferase (GST) activity with concomitant increase in 2′,7′-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substances (TBARS) production. Similarly, decreased testicular and epididymal NO level with concomitant elevation in arginase activity was observed in hypertensive rats. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations in biomarkers of reproductive function in hypertensive rats. The inhibition of arginase activity and increase in NO and testosterone levels by both rhizomes could suggest possible mechanism of action for the prevention of male infertility in hypertension. Therefore, both rhizomes could be harnessed as functional foods to prevent hypertension-mediated male reproductive dysfunction.
Effects of Alcohol on the Endocrine System
2013, Endocrinology and Metabolism Clinics of North America
Citation Excerpt :
NO, also synthesized in the testes, has been suggested as another player in the alcoholic's reduced production of testosterone. Inhibition of nitric oxide synthase, the enzyme responsible for NO synthesis, prevents the decrease in testosterone associated with alcohol drinking.77 The action of PRL action on the mammary gland and in the maintenance of lactation has long been known and is the source of the name for this hormone.
Asymmetric dimethylarginine as a prognostic marker for cardiovascular complications in hypertensive patients
2011, Egyptian Heart Journal
Citation Excerpt :
Additionally, diminished nitric oxide bioactivity may facilitate vascular inflammation that could lead to oxidation of lipoproteins and foam cell formation, the precursor of the atherosclerotic plaque. Accordingly, there is a causal relationship between improved endothelial function and reduction in myocardial ischemia and acute coronary events,26,27 and this was proved in our study, as the lowest significant serum level of NO was present in group I (patients with complicated hypertension) to the control group. Heibashy and Abdel Moniem28 reported that; the endothelial dysfunction in hypercholesterolemic individuals could be related to plasma concentration of ADMA, which is a strong independent predictor of overall mortality and cardiovascular outcome in hemodialysis patients, and increased plasma concentrations of ADMA have been reported in hypertension and pre-eclampsia.
Hypertension has a serious harmful effect on the physiological and biochemical functions of heart that end with the appearance of cardio-vascular diseases. Asymmetric dimethylarginine (ADMA) has evolved as an important regulator of nitric oxide (NO) synthesis. The relationship between ADMA and essential hypertension has been scarcely explored. This study is aiming to investigate the physiological, pathological, and biochemical roles of plasma ADMA in relation to serum nitric oxide and also the relation between ADMA and NO with other traditional cardiovascular risk factors in hypertensive patients.
The study was designed as a prospective case-control study which included 60 hypertensive cardiovascular patients and 10 healthy volunteers as a control group. The patients were divided into four groups: hypertension with cardiovascular complications, uncontrolled hypertension (blood pressure >139/89), controlled hypertension, and control group. Levels of ADMA and nitric oxide were assessed and statistically correlated to other clinical and laboratory values [cholesterol, triglycerides, urea, creatinine, and fasting and postprandial blood sugar].
The plasma ADMA level in group I was significantly increased (2.29 ± 0.06 μmol/L) compared to control group (0.55 ± 0.05 μmol/L) P = 0.001 and also serum NO level was significantly decreased in this group (11.65 ± 0.75 μmol/L) compared to control group (52.11 ± 1.43 μmol/L) P = 0.001. This group had variable complications, e.g., ischemic heart disease, pulmonary hypertension, pulmonary embolism, and cerebrovascular disease. Group II: plasma ADMA level was significantly increased in this group (1.41 ± 0.06) and also serum NO level was significantly decreased (30.91 ± 1.31) compared to control group (P = 0.001). Group III: they had a lower plasma level of ADMA (1.11 ± 0.05) compared to groups I and II (P value: 0.001) and significantly higher than the control group. The serum NO level was significantly decreased (40.01 ± 0.67) compared to control group and significantly higher than groups I and II. Hypertensive groups I, II, and III showed a significant increase in mean fasting and postprandial blood sugar (171.4 ± 71.00, 143.64 ± 37.00, and 137.00 ± 27.06 mg/dl, respectively) compared to control group (85.32 ± 13.17 mg/dl). Urea, creatinine, cholesterol, and triglycerides in the hypertensive groups (I, II, and III) showed a significant increase compared to control group with significant positive correlation in relation to ADMA.
ADMA is elevated in hypertensive patients. Elevated ADMA concentrations are associated with impaired endothelium functions, which are demonstrated by NO reduction in the sera of hypertensive patients. ADMA is correlated positively with the traditional cardiovascular risk factors. Also there was a strong significant negative correlation between NO and ADMA levels in the whole hypertensive groups.
Avian Testicular Structure, Function, and Regulation
2011, Hormones and Reproduction of Vertebrates - Volume 4
This chapter focuses on the avian testicular structure, function, and regulation. The testes undergo dramatic annual changes in size in many birds. Adult testicular function is modulated by a myriad of external factors and orchestrated by numerous hormones that together enable birds to adapt to and breed in diverse habitats worldwide. These factors have generated a wide range of avian reproductive strategies, which has further shaped testicular structure and function. The chapter describes the mechanisms that control avian exocrine and endocrine testicular functions. It analyzes how these functions are regulated by ecological and behavioral factors and presents an overview of how environmental information is integrated and transduced into appropriate gonadal responses. It also discusses testicular dysfunction and the potential effects of anthropogenic disturbances on testis function.

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Pharmacology lettersNitric oxide control of steroidogenesis: Endocrine effects of NG-nitro-L-arginine and comparisons to alcohol

Abstract

TIPS

Mol. Cell. Endocrinol.

J. Biol. Chem.

TIPS

Biochem. Pharmacol.

Pharmacol. Rev.

Nature

Nature

Br. J. Pharmacol.

FASEB J.

Pharmacology letters
Nitric oxide control of steroidogenesis: Endocrine effects of N^G-nitro-L-arginine and comparisons to alcohol