Rat testicular interstitial fluid contains mediators of vasopermeability

Tapanainen, J; Paloneva, T; Veijola, M.; Rajaniemi, Hannu

doi:10.1530/jrf.0.0890723

Cited by 7 publications

(7 citation statements)

References 11 publications

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“…These results confirm an adverse effect of imidazoles on male reproductive function [15][16][17][18] and support the hypothesis that imidazoles inhibit male fertility through suppression of two important aspects of testicular function: testosterone secretion and TIF formation [12,13,[32][33][34][35][36]. The results also suggest that imidazoles can disrupt pituitary LH secretion regulatory mechanisms.…”

Section: Discussionsupporting

confidence: 85%

“…TIF testosterone levels reflect testosterone secretion inside the testes, where it exerts paracrine and autocrine effects on steroidogenesis and spermatogenesis [30,31]. TIF volumes have been measured to assess TIF formation and vascular perfusion inside the testis [13,32,33] that control access of important substances to testicular cells and structures [32,[34][35][36]. Disruption of TIF paracrine control systems is thought to be a major cause of idiopathic infertility in men [30], so these TIF measures reflect important aspects of gonadal function.…”

Section: Introductionmentioning

confidence: 99%

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Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo1

Adams

Meyer

Cicero

1998

Biology of Reproduction

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The aim of these studies was to examine the effects of imidazoles on testosterone secretion and testicular interstitial fluid (TIF) formation through measurement of serum LH, serum testosterone, TIF testosterone, and TIF volumes. Imidazole, 1-methylimidazole, 4-methylimidazole (4-MI), and ketoconazole, an oral imidazole antifungal agent, caused dose-dependent decreases in testosterone secretion and TIF formation. Imidazole, 2-methylimidazole, and 4-MI decreased LH secretion. 4-MI decreased testosterone secretion 1-6 h after injection, increased testosterone at 8-16 h, decreased LH secretion at 4 h, decreased TIF volumes at 1-8 h, and slightly increased TIF volumes at 24 h. 4-MI blocked the stimulatory effects of hCG on testosterone secretion and prevented an expected increase in LH secretion after the 4-MI-induced decrease in testosterone secretion. 4-MI also reversed the effects of three other stimulants of testosterone secretion that presumably act through three different testicular regulatory systems: N-methyl-D,L-aspartate, an excitatory amino acid; NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor; and naltrexone, an opioid antagonist. These results support the hypothesis that imidazoles inhibit testicular function and male reproductive function through inhibition of testosterone secretion, TIF formation, and LH secretion regulatory systems.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo1

Adams

Meyer

Cicero

1998

Biology of Reproduction

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“…Additionally, Doxa could exert important vascular effects (16) including the change of blood flow in the testes and affect TIF volume/content because TIF formation/volumes reflect testis vascular perfusion (73). This phenomenon would decrease the amount of LH delivered to Leydig cells and impair entrance of androgens from TIF to the testicular microvasculature by restriction in movement of testosterone across the endothelial barrier (62), especially since the rat TIF contains mediators of vasopermeability (74). The picture about in vivo DoxaϩIMO effects could be even more complicated, since testicular blood flow exhibits vasomotion, the process sensitive to catecholamines (11,12).…”

Section: E199 Doxazosin Mitigates Stress-disturbed Leydig Cell Steroimentioning

confidence: 99%

Sustained in vivo blockade of α₁-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells

Stojkov

Janjic

Baburski

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Stojkov NJ, Janjic MM, Baburski AZ, Mihajlovic AI, Drljaca DM, Sokanovic SJ, Bjelic MM, Kostic TS, Andric SA. Sustained in vivo blockade of ␣ 1-adrenergic receptors prevented some of stresstriggered effects on steroidogenic machinery in Leydig cells. Am J Physiol Endocrinol Metab 305: E194 -E204, 2013. First published May 14, 2013 doi:10.1152/ajpendo.00100.2013.-This study was designed to systematically analyze and evaluate the effects of in vivo blockade of ␣ 1-adrenergic receptors (␣1-ADRs) on the stress-induced disturbance of steroidogenic machinery in Leydig cells. Parameters followed 1) steroidogenic enzymes/proteins, transcription factors, and cAMP/testosterone production; 2) the main hallmarks of stress (epinephrine, glucocorticoids); and 3) transcription profiles of ADRs and oxidases with high affinity to inactivate glucocorticoids. Results showed that sustained blockade of ␣ 1-ADRs prevented stress-induced 1) decrease of the transcripts/proteins for main steroidogenic CYPs (CYP11A1, CYP17A1); 2) decrease of Scarb1 and Hsd3b1 transcripts; 3) decrease of transcript for Nur77, one of the main activator of the steroidogenic expression; and 4) increase of Dax1 and Arr19, the main steroidogenic repressors in Leydig cells. In the same cells, the expression of steroidogenic stimulatory factor Creb1, StAR, and androgen receptor increased. In this signaling scenario, stress-induced stimulation of Adra1a/Adra1b/Adrbk1 and Hsd11b2 (the unidirectional oxidase with high affinity to inactivate glucocorticoids) was not changed. Blockade additionally stimulated stress-increased transcription of the most abundantly expressed ADRs Adra1d/Adrb1/Adrb2 in Leydig cells. In the same cells, stress-decreased testosterone production, the main marker of Leydig cells functionality, was completely prevented, while reduction of cAMP, the main regulator of androgenesis, was partially prevented. Accordingly, the presented data provide a new molecular/transcriptional base for "fight/adaptation" of steroidogenic cells and new molecular insights into the role of ␣1-ADRs in stress-impaired Leydig cell steroidogenesis. The results are important in term of wide use of ␣1-ADR selective antagonists, alone/in combination, to treat high blood pressure, nightmares associated with posttraumatic stress disorder, and disrupted sexual health. testosterone; stress; ␣1-adrenergic receptors; steroidogenic machinery; doxazosin TESTOSTERONE-PRODUCING LEYDIG CELLS, like all other steroidproducing cells, synthesize steroid hormones from common precursor cholesterol using the steroidogenic machinery (Fig. 1). This complex machinery is comprised of cholesterol transporters (50, 56, 71), steroidogenic enzymes (51), and many regulatory molecules (17,18,50,51,56,71) as well as numerous transcriptional factors controlling the expression of steroidogenic gene expression (33,40,69). The steroidogenic function of Leydig cells is predominantly regulated by pituitary luteinizing hormone (LH) or its placental counterpart, human chorionic gonadotropin (hCG). LH/hCG re...

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“…The androgens levels in total TIF volume, extracted from testicular tissue and released in medium decreased after 19Doxa treatment, but returned to control levels after 109Doxa application. Discrepancy between androgens levels in TIF and circulation could be explained by the possibility that Doxa application could eventually affect entrance of androgens from TIF to testicular microvasculature by restriction in movement of testosterone across the endothelial barrier (Setchell et al, 2002), especially because the rat TIF contains mediators of vasopermeability (Tapanainen et al, 1990). In addition, although there is no published data about effect of Doxa on androgens/steroids metabolic clearance it is possible that systemic in vivo Doxa application could affect metabolic rate of testosterone as Doxa affected vasculature, metabolism and hepatic vascular resistance (Dell'Omo et al, 2005).…”

Section: (A) (B) (D) (C)mentioning

confidence: 99%

Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats

et al. 2012

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SUMMARYDoxazosin (Doxa) is an a1-selective adrenergic receptor (ADR) antagonist widely used, alone or in combination, to treat high blood pressure, benign prostatic hyperplasia symptoms, and recently has been suggested as a potential drug for prostate cancer prevention/treatment. This study was designed to evaluate the effect of in vivo Doxa po-application, in clinically relevant dose, on: (i) steroidogenic machinery homeostasis; (ii) cAMP/cGMP signalling; (iii) transcription profile of ADR in Leydig cells of adult rats. The results showed that po-application of Doxa for once (19Doxa), or for two (29Doxa) or 10 (109Doxa) consecutive days significantly disturbed steroidogenic machinery homeostasis in Leydig cells. Doxa po-application significantly decreased circulating luteinizing hormone and androgens levels. The level of androgens in testicular interstitial fluid and that extracted from testes obtained from 19Doxa/29Doxa rats decreased, although it remained unchanged in 109Doxa rats. Similarly, the ex vivo basal androgen production followed in testes isolated from 19Doxa/29Doxa rats decreased, while remained unchanged in 109Doxa rats. Differently, ex vivo testosterone production and steroidogenic capacity of Leydig cells isolated from 19Doxa/29Doxa rats was stimulated, while 109Doxa had opposite effect. In the same cells, cAMP content/release showed similar stimulatory effect, but back to control level in Leydig cells of 109Doxa. 19Doxa/29Doxa decreased transcripts for cAMP specific phosphodiesterases Pde7b/Pde8b, whereas 109Doxa increased Pde4d. All types of treatment reduced the expression of genes encoding protein kinase A (PRKA) regulatory subunit (Prkar2b), whereas only 109Doxa stimulated catalytic subunit (Prkaca). Doxa application more affected cGMP signalling: stimulated transcription of constitutive nitric oxide synthases (Nos1, Nos3) in time-dependent manner, whereas reduced inducible Nos2. 109Doxa increased guanylyl cyclase 1 transcript and PRKG1 protein in Leydig cells. Orally applied Doxa significantly disturbed the transcriptional 'signature' of steroidogenic machinery, cAMP/cGMP signalling and ADRs and b-ADRs kinases in Leydig cells, thus giving new molecular insights into the role of cAMP/cGMP/adrenalin signalling in Leydig cells homeostasis.

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Rat testicular interstitial fluid contains mediators of vasopermeability

Abstract: Summary. An

Cited by 7 publications

References 11 publications

Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo1

Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo1

Sustained in vivo blockade of α₁-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells

Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats

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Rat testicular interstitial fluid contains mediators of vasopermeability

Abstract: Summary. An

Cited by 7 publications

References 11 publications

Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo1

Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo1

Sustained in vivo blockade of α1-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells

Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats

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Sustained in vivo blockade of α₁-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells