Ossido nitrico e possibile doppia azione sull'asse gonadico

[emcar]

Ciao Ragazzi,
e ciao Guru in particolare.

Leggevo delle cose su Pub Med e mi sono trovato per caso a leggere una cosa che non sapevo e cioè che la molecola di ossido nitrico (NO) a livello testicolare inibisce la produzione di testosterone.

Gianni so che te sei esperto di arginina e del suo ruolo di promuovere il NO che a sua volta andrebbe a stimolare la produzione LHRH ma sembra che però a livello periferico il risulatato sia l'opposto.


Vi allego degli studi:

D-Aspartic acid and nitric oxide as regulators of androgen production in boar testis.
Lamanna C, Assisi L, Vittoria A, Botte V, Di Fiore MM.
Source
Department of Life Sciences, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy.
Abstract
D-Aspartic acid (D-Asp) and nitric oxide (NO) are two biologically active molecules playing important functions as neurotransmitters and neuromodulators of nerve impulse and as regulators of hormone production by endocrine organs. We studied the occurrence of D-Asp and NO as well as their effects on testosterone synthesis in the testis of boar. This model was chosen for our investigations because it contains more Leydig cells than other mammals. Indirect immunofluorescence applied to cryostat sections was used to evaluate the co-localization of D-Asp and of the enzyme nitric oxide synthase (NOS) in the same Leydig cells. D-Asp and NOS often co-existed in the same Leydig cells and were found, separately, in many other testicular cytotypes. D-Asp level was dosed by an enzymatic method performed on boar testis extracts and was 40+/-3.6 nmol/g of fresh tissue. NO measurement was carried out using a biochemical method by NOS activity determination and expressed as quantity of nitrites produced: it was 155.25+/-21.9 nmol/mg of tissue. The effects of the two molecules on steroid hormone production were evaluated by incubating testis homogenates, respectively with or without D-Asp and/or the NO-donor L-arginine (L-Arg). After incubation, the testosterone presence was measured by immunoenzymatic assay (EIA). These in vitro experiments showed that the addition of D-Asp to incubated testicular homogenates significantly increased testosterone concentration, whereas the addition of L-Arg decreased the hormone production. Moreover, the inclusion of L-Arg to an incubation medium of testicular homogenates with added D-Asp, completely inhibited the stimulating effects of this enantiomer. Our results suggest an autocrine action of both D-Asp and NO on the steroidogenetic activity of the Leydig cell
Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle.
Di Fiore MM, Lamanna C, Assisi L, Botte V.
Source
Department of Life Sciences, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy. MariaM.difiore@unina2.it
Abstract
D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis.
METHODS:
By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels.
RESULTS:
IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited.
CONCLUSION:
Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.



Voi cosa sapete in merito?

[SuperFabio]

Davvero interessante ciò che riporti. Benchè si sappia da molto che il daa alzi la produzione di testosterone è nuova (per me si intende) che il NO agisca da antagonista alla genesi di testosterone nelle gonadi. Aspettiamo il parere di qualche maestro

[emcar]

Altri riferimenti

Male reproductive ageing: using the brown Norway rat as a model for man.
Wang C, Hikim AS, Ferrini M, Bonavera JJ, Vernet D, Leung A, Lue YH, Gonzalez-Cadavid NF, Swerdloff RS.
SourceDepartment of Medicine, Harbor-UCLA Medical Center and Research and Education Institute, Carson, CA 90509, USA.

Abstract
The Brown Norway (BN) rat is an excellent model for male reproductive ageing. We and others have shown that with ageing, the BN rat exhibits low serum testosterone, low Leydig cell steroidogenic capacity, decreased Sertoli cell function and number, marked reduction in seminiferous tubule volume and sperm content, and accelerated germ cell apoptosis. These testicular changes are the result of a combination of a primary testicular defect and a secondary hypothalamic dysfunction. Leydig cell dysfunction results from decreased activities of the steroidogenic enzymes and Leydig cell secretory capacity and is not corrected by daily administration of replacement luteinizing hormone (LH), suggesting a primary testicular defect. However ageing in male BN rats is associated with decreased LH pulse amplitude, reduced gonadotropin releasing hormone (GnRH) and gonadotropin responsiveness to excitatory amino acids, and decreased GnRH mRNA and peptide in the hypothalamus. We have further shown in the hypothalamus of ageing BN rats that while the excitatory amino acid receptor content is reduced, nitric oxide synthase (NOS) activity is increased which is due to increased inducible (iNOS) but not neuronal NOS (nNOS). The increased iNOS protein in the hypothalamus is associated with increased peroxynitrite formation and neuronal cell apoptosis. We conclude that increased hypothalamic levels of iNOS may result in neurotoxicity in the hypothalamus leading to loss of hypothalamic GnRH secretory cells and impaired GnRH pulsatile secretion that contributes to the abnormal Leydig cell function characteristic of male reproductive ageing

Involvement of nitric oxide synthase in the mechanism of histamine-induced inhibition of Leydig cell steroidogenesis via histamine receptor subtypes in Sprague-Dawley rats.
Mondillo C, Pagotto RM, Piotrkowski B, Reche CG, Patrignani ZJ, Cymeryng CB, Pignataro OP.
SourceLaboratory of Molecular Endocrinology and Signal Transduction, Institute of Biology and Experimental Medicine-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), CP 1428, Buenos Aires, Argentina. mondillo@dna.uba.ar

Abstract
This study was conducted to shed light on the so far unexplored intracellular mechanisms underlying negative modulation of Leydig cell steroidogenesis by histamine (HA). Using the MA-10 cell line and highly purified rat Leydig cells as experimental models, we examined the effect of the amine on biochemical steps known to be modulated by HA or involved in LH/hCG action. In agreement with previous findings, HA at 10 microM showed a potent inhibitory effect on hCG-stimulated steroid synthesis, regardless of the gonadotropin concentration used. Moreover, HA decreased not only LH/hCG-induced cAMP production but also steroid synthesis stimulated by the permeable cAMP analog dibutyryl cAMP (db-cAMP). Considering the post-cAMP sites of HA action, it is shown herein that HA markedly inhibited db-cAMP-stimulated steroidogenic acute regulatory (STAR) protein expression, as well as steps catalyzed by P450-dependent enzymes, mainly the conversion of cholesterol to pregnenolone by cholesterol side-chain cleavage enzyme (CYP11A). The antisteroidogenic action of HA was blocked by addition of the phospholipase C (PLC) inhibitor U73122, and HA significantly augmented inositol triphosphate (IP3) production, suggesting a major role for the PLC/IP3 pathway in HA-induced inhibition of Leydig cell function. Finally, HA increased nitric oxide synthase (NOS) activity, and the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) markedly attenuated the effect of the amine on steroid synthesis. On the basis of our findings, HA antagonizes the gonadotropin action in Leydig cells at steps before and after cAMP formation. NOS activation is the main intracellular mechanism by which HA exerts its antisteroidogenic effects.

[emcar]

Alteration in male reproductive system in experimental cholestasis: roles for opioids and nitric oxide overproduction.
Kiani S, Valizadeh B, Hormazdi B, Samadi H, Najafi T, Samini M, Dehpour AR.
SourceDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

Abstract
Cirrhosis is associated with impairment of the male reproductive system, hypogonadism and feminization. It is important to rule out whether the impairment in the reproductive system exists earlier in the course of cholestatic liver disease to target effective therapies at the best time point. In this study we investigated the role of endogenous opioid and nitric oxide system in alterations of the reproductive system in male rats. We performed sham or bile duct ligation surgery on male Sprague-Dawley rats and treated the animals for seven days with saline, naltrexone, an opioid receptor blocker (20 mg/kg) and N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (10 mg/kg). We then evaluated the plasma level of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), sperm count and motility as well as biomarkers of cholestasis and nitric oxide productions. The results showed that following cholestasis, total testosterone level decrease and LH level increase in plasma of cholestatic rats and treatment with L-NAME and naltrexone could improve the plasma level of testosterone. Naltrexone could decrease the elevated level of LH in cholestatic animals. In addition, the weight of seminal vesicles and prostate significantly decreased in cholestasis as compared to the control group and treatment with L-NAME and naltrexone could improve the weights of the two organs in cholestasis. Our results demonstrate for the first time that the male reproductive system is impaired early in cholestasis and that endogenous opioid and nitric oxide system contribute to these impairments in the early course of the disease.

[emcar]

RAGA......

Ma qualche esperto di integrazione che dica qualcosa???

NOn ci credo che nessuno ne sappia nulla

Sono il primo ad aver letto una cosa simile?'
Anche se fosse nessuno esprime il suo parere??

[Gianlu.....]

Ciao Ema,mi limito a scrivere per salutarti.. non so esprimere il mio parere in merito, e non ho mai integrato con stimolatori di NO

[emcar]

Grazie Gianlu,
si immaginavo tu non ne avessi mai usati.
Però sul forum vedo sempre un sacco di persone che si informano su tutti i tipi di preworkout per il pump ed immaginavo quindi che ci fossero più persone che potessero dire il loro pensiero.

Aspetterò cosa ne pensi Guru.

[Gianlu.....]

si, sembra strano pure a me ci siano state cosi poche risposte...

[ilsecco]

non ho capito se il test è stato fatto su umani o su animali....

[Thebro]

I test sugli animali sono sempre da verificare, ancor meno validi quelli riguardanti stati patologici (cirrosi).

Il discorso è però se si riesce a stimolare la produzione di NO nel testicolo con le "integrazioni " che usiamo di solito, i testicoli un pò come il cervello, sono più "protetti" si parla di barriera ematotesticolare, quindi bisognerebbe valutare se le sostanze tipo arginina & co. o nootropi riesono a raggiungere le cellule del Leyding.

Niente si dice su come è stata stimolata la produzione di NO......non mi sembrano studi di rilievo.

[lupin III]

Io ricordo ben altro in merito all'ossido di azoto.
In questi giorni do un'occhiata e poi un parere, fermo restando che il primo studio e' sui testicoli dei cinghiali e non vale una sega.

[emcar]

Si gli studi sono animali,
però due articoli sono riuscito a scaricarli e si parla, nelle introduzione dell'articolo, del fatto che è noto che NO ha un ruolo inibente a livello testicolare sulla prodizione di testosterone.
Sinceramente l'approccio " e' sugli animali quindi non conta una sega" mi sembra un approccio un po' ottuso.
Io ho postato queste cose perchè sono rimasto anche io un po' perplesso non volevo mica sconvolgere il mondo degli utilizzatori di di preworkout a base di stimlanti di NO.

Altra cosa se gli studi sugli animali non contano ( e può essere vero) fatemene vedere alcuni (che come ha scritto Lupin) dicono ben altro e sull'uomo.

[emcar]

Al massimo più che dire che è sugli animali potevate obiettare che sono in vitro.

[lupin III]

Non ho detto che gli studi sugli animali non contano una sega, ho parlato del primo che e' stato fatto sui cinghiali.
Sai leggere? Credi che fare uno studio sui cinghiali o sui ratti sia la medesima cosa?
No, conta anche il tipo di animale sui cui e' stato svolto...
Questo solo per spiegare il mio "approccio un po' ottuso".
Data la cortesia la risposta cercala da te.

[greatescape]

gli studi sugli animali dovrebbero essere una specie di campanello d' allarme per noi
come dice lupin sono validi ma non significativi, si insomma sono da prendere un po' con le pinze
in america molti produttori di integratori vendono prodotti sbandierando studi e performance dietro, anche se poi scopri che quei studi li erano stati fatti sui topi e basta
tipo pianta africana x aumento del testosterone del 700% ecc