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R Mioni

Publications and source records attributed to R Mioni.

At least 37 records · Page 2Linked to original sources

The role of calcium ions in rat Leydig cell steroidogenesis induced by atrial natriuretic peptide.

The aim of this study was to clarify whether calcium ions play a role in the mechanisms by which rat atriopeptin II exerts its stimulatory effects on rat Leydig cell steroidogenesis. The absence of calcium in the medium and the calcium channel-blocker drug, verapamil, both significantly inhibited testosterone production in rat atriopeptin II-treated rat Leydig cells. Similar effects were observed on human chorionic gonadotropin-stimulated Leydig cells. Furthermore, 8-Bromoguanosine 3':5' cyclic monophosphate, the putative second messenger of atrial natriuretic peptide, significantly increased rat Leydig cell steroidogenesis, determining a stimulatory effect comparable to that obtained with rat atriopeptin II. Calcium-free medium and verapamil inhibited this stimulatory effect. The addition of a calcium ionophore. A-23187, significantly counteracted the inhibitory effect of verapamil on rat atriopeptin II-induced and 8-Bromoguanosine 3':5' monophosphate-induced testosterone production. Furthermore, rat atriopeptin II significantly stimulated the calcium flux through the plasma membrane, as evaluated by the 45Ca2+ uptake method. This effect was strongly inhibited by the addition of verapamil. These data underline that calcium ions may play a role in the mechanisms by which atriopeptin II stimulates rat Leydig steroidogenesis, although other post-receptor systems cannot be excluded.

Analysis of Variance↗

Evidence for specific binding and stimulatory effects of recombinant human erythropoietin on isolated adult rat Leydig cells.

The presence of specific binding of recombinant human erythropoietin and its effect on testosterone production were evaluated in isolated intact adult rat Leydig cells. Maximal specific binding was observed after 135 min incubation at 34 degrees C. Scatchard analysis of the binding data revealed two distinct classes of binding sites for [125I]-recombinant human erythropoietin with dissociation constant of (Kd1) 1.9 x 10(-10) mol/l and (Kd2) 1.37 x 10(-8) mol/l respectively and binding capacity of (Bmax1) 12.3 fmol/10(6) cells and (Bmax2) 42.8 fmol/10(6) cells, respectively. GnRH, hCG, IGF-I and EGF did not induce any modification of recombinant human erythropoietin-specific binding. Recombinant human erythropoietin added to isolated adult rat Leydig cells exerted a stimulatory effect on testosterone production reaching its maximal effect at the dose of 10(-10) mol/l (testosterone production from 14.9 +/- 1.7 to 45.1 +/- 6.2 pmol/10(6) cells/3 h). Addition of anti-recombinant human erythropoietin serum completely blocked the recombinant human erythropoietin-stimulated testosterone production. These results show that purified adult rat Leydig cells possess recombinant human erythropoietin specific binding, and suggest that this glycoprotein directly influences rat Leydig steroidogenesis.

Animals↗

Evidence for the involvement of sperm angiotensin converting enzyme in fertilization.

Recently it has been observed that ejaculated human sperm possess high angiotensin converting enzyme (ACE) activity and that this enzyme is released during the process of capacitation. This observation raises the possibility that ACE may be involved in the fertilization process. To verify this hypothesis, we tested the effects of a potent ACE inhibitor, Captopril, on acrosome reaction induced by capacitating medium (3.5% HSA-added BWW) and on ability of human capacitated spermatozoa to penetrate zona-free hamster oocytes. Addition of Captopril (100 nmol l-1) modified neither sperm motility nor viability at any time considered, but significantly reduced the acrosome reaction percentages of sperm incubated in capacitating medium. Furthermore, Captopril significantly reduced the percentage of penetrated oocytes. The mean penetration rates both in the absence and presence of Captopril were 65.5 +/- 4.9% and 26.9 +/- 2.3% (P less than 0.001) respectively. These findings provide evidence that sperm release of ACE during capacitation may have a physiological role in the regulation of the mechanisms that allow sperm acrosome reaction and thus fertilizability.

Acrosome↗

Stimulatory effects of alpha-hANP on testosterone secretion in man.

Several recent observations suggest that atrial natriuretic peptides (ANP) can modulate steroidogenesis in isolated rat Leydig cells. At present, it is unknown whether ANP influence human testicular steroidogenesis. We therefore evaluated the effects of alpha-human ANP (hANP) administration on testosterone plasma levels in peripheral and internal spermatic venous blood of young men (catheterized for contrast study of varicocele). Six subjects were injected with 100 micrograms alpha-hANP in the cubital vein. Six different patients similarly received 50 micrograms LHRH. Three controls received 2 ml saline. Plasma LH, FSH, and testosterone were then determined 15 min before, at time of injection, and 15, 30, 45, and 60 min thereafter in spermatic vein and peripheral venous blood, as well as at 120 min in peripheral blood. LHRH--induced LH increase was followed by a marked increase of spermatic vein testosterone concentrations, but the peripheral testosterone concentration did not increase. Similarly, alpha-hANP administration did not affect peripheral testosterone and LH concentrations, but significantly increased spermatic vein testosterone levels (P less than 0.01). Our findings demonstrate that alpha-hANP exerts its stimulatory effect on testicular steroidogenesis in man without modifying gonadotropin secretion, suggesting that alpha-hANP may directly influence Leydig cell function.

Adolescent↗

Evidence for a dopaminergic involvement in the inhibitory effect of alpha human natriuretic peptide on prolactin in man.

Recently, it has been suggested that Atrial Natriuretic Peptides (ANP), as well as peripheral hormones, may have a role as central neurotransmitters or neuromodulators, and in humans it has been observed that alpha human ANP inhibits prolactin secretion. In this study, on 12 normal adult males, we evaluated the effects of ANP on the prolactin release induced by TRH and by the dopaminergic blocker sulpiride. Alpha-hANP administration was followed by a significant fall of prolactin plasma levels but did not influence TRH-induced prolactin response. Nevertheless, sulpiride-induced prolactin secretion was significantly lower after Alpha-hANP administration than after placebo pre-treatment (p values ranging between 0.01 and 0.001). Our results suggest that in man Alpha-hANP has no direct influence on lactotrope cells in inhibiting prolactin secretion, but seems to involve activation of the hypothalamic dopaminergic system.

Adult↗

Effects of atrial natriuretic factor (ANF) on rat testicular steroidogenesis in vitro.

The aim of this study was to evaluate the effects of rat atrial-peptide type II (rAP-II) on testicular steroidogenesis by isolated adult rat Leydig cells. rAP-II stimulates testosterone secretion. The maximal stimulatory effects of rAP-II on testosterone production occurred at the dose of 10(-11) M. At the same dose this peptide stimulates androstenedione and dehydroepiandrosterone-sulphate production, two important testosterone precursors of delta-4 and delta-5 steroidogenetic pathways, respectively. At higher doses, 10(-9) and 10(-7) M, the stimulatory effect of rAP-II on testosterone secretion is strongly declined, on androstenedione secretion is abolished, whereas on dehydroepiandrosterone-sulphate secretion remains unaffected. These data suggest that rAP-II at low doses exerts a stimulatory effect on the early steroidogenetic step by isolated adult rat Leydig cells. At higher doses this peptide seems to influence the testicular steroidogenesis, probably exerting a limiting reaction step involving the 3-beta-OH-steroid-dehydrogenase activity.

Androstenedione↗

Specific binding and steroidogenetic effects of atrial natriuretic factor (ANF) in Leydig cells of rats.

Atrial natriuretic factors (ANF) may influence testicular steroidogenesis. This study was conducted to evaluate the presence of specific ANF-binding on isolated adult rat Leydig cells and the effects of ANF on testosterone production. Indirect immunofluorescence technique demonstrates that adult rat Leydig cells possess specific ANF-binding and that rAP-II strongly stimulates the testosterone production. rAP-II exerts its maximal stimulatory effect on the testosterone secretion at low doses (10(-11) M), corresponding at the physiological plasmatic concentration in the adult normal rat. High doses (10(-9)-10(-7) M) of rAP-II show a decline in the stimulatory effect on testosterone secretion. Our data suggest that rAP-II influences the testicular steroidogenesis by a receptorial mechanism; the biphasic effect of rAP-II on the testosterone production may be related to an acute receptorial desensitization phenomena.

Animals↗

Evidence for serotoninergic system involvement in opioid control of luteinizing hormone secretion in man.

Endogenous opioid peptides tonically inhibit LH by acting on hypothalamic mechanisms which regulate LHRH secretion. Opiates increase hypothalamic serotonin turnover but the involvement of the serotoninergic system in the opioid mechanisms regulating LH secretion in man is not clear at present. This study was designed to evaluate whether the tonic inhibitory effect on LH secretion induced by opiates involves the serotoninergic system. We have studied 10 healthy young men (aged 20-28 years). Five subjects were infused with naloxone (10 mg/h for 3 h) before and 120 min after fenfluramine administration (60 mg orally) on two different occasions. In five other subjects naloxone was infused before and after metergoline pretreatment (8 mg on first and second day and 4 mg on the third day, orally, at 0 time of naloxone infusion). After fenfluramine, naloxone infusion failed to induce any increase in LH plasma levels; metergoline pretreatment significantly enhanced the naloxone-induced LH increase. These data suggest that in man a hypothalamic serotoninergic system may be involved in the opioid mechanisms regulating LH secretion.

Adult↗

Osteoporosis and decline of gonadal function in the elderly male.

The bone mineral content was evaluated in 30 male subjects aged between 60 and 90 years using the relief of the percent cortical area (PCA) at the level of the second phalanx of the left-hand index finger, by Garn's method. This was to evaluate the rate of bone loss with increasing age. Testosterone, androstenedione, estrone, 17 beta-estradiol plasma levels were determined in all subjects by the RIA method. 60% of our patients showed increased bone resorption (PCA less than 55%); in these subjects testosterone and androstenedione plasma levels were significantly lower than in subjects not affected by osteoporosis. A positive linear correlation is evident between PCA and testosterone, androstenedione and estrone plasma levels. Thus, like in women, decline of gonadic function determines an increased bone resorption in men too.

Aged↗

Male hypogonadism in aorto-iliac arteriopathies.

In 43 patients affected by aorto-iliac arteriopathies, gonadotropins, testosterone, androstenedione serum levels were measured to verify the presence of a testicular alteration secondary to ischemia. Important signs of testiculopathies (increased gonadotropins and decreased testosterone serum levels) were observed in patients with flow alteration of the internal spermatic artery and in patients with obstructions of the common iliac. Plasma androstenedione levels were not decreased while the A/T ratio was increased in hypotestosteronemic patients. Ischemia might determine a functional block of 17 beta reductase enzyme, necessary to convert androstenedione to testosterone. The impotentia coeundi, which affected about 50% of our patients is not related to testosteronemia.

Adult↗

Effects of successful renal transplantation on left ventricular mass.

Left ventricular hypertrophy is an independent cardiovascular risk factor in the general population and in patients with chronic renal failure. Relatively little is known about the effects of renal transplantation on left ventricular hypertrophy. The aim of this study was to determine the changes in left ventricular mass after successful renal transplantation and to evaluate the importance of some clinical, laboratory, and echocardiographic variables on the trend to left ventricular hypertrophy. Twenty-three patients with end-stage renal disease were studied by ambulatory blood pressure monitoring and echocardiography before and 2 years following renal transplantation. After 24 months of follow-up, all transplant recipients had adequate renal function (serum creatinine <2 mg/dL). At the end of the study, we observed a significant decrease in left ventricular mass and left ventricular mass index compared to the pretransplantation period. In renal transplant recipients, the prevalence of left ventricular hypertrophy significantly decreased (78% versus 44%, P < .03) after 2 years of follow-up. Systolic 24-hour blood pressure was the only predictor of left ventricular mass and of left ventricular mass index at 2 years after transplantation. In conclusion, successful renal transplantation produces a regression of left ventricular hypertrophy. This beneficial effect depends on a decrease in systolic pressure levels.

Adult↗

Effects of naloxone on gonadotropin secretion in Klinefelter syndrome.

To study the opioid control on LH and FSH secretion in Klinefelter subjects (KS), the response of gonadotropin to an opioid antagonist, naloxone, was examined in 8 KS (age range 25-35 yrs) and in 8 age matched normal men. In 6 KS with low testosterone plasma levels, naloxone infusion were also performed after treatment with testosterone enanthate, 200 mg i.m. every 3 weeks for 4 months. FSH did not show any important variation in KS and in normal men during naloxone infusion. In KS the percentage of naloxone induced LH increase was significantly lower than in controls and there was no correlation between testosterone plasma levels and LH increase after naloxone infusion. LH increases after naloxone infusion were not significantly different before and after testosterone treatment. The increases of naloxone induced LH plasma levels, before and after testosterone treatment, correlated well between themselves (r = 0.93-p less than 0.01). Plasma levels decreased in all patients after testosterone treatment, but only in two was there a return to normal range. There is a clearly positive linear correlation between the percentage of LH decrease after testosterone treatment and LH increase after naloxone infusion (r = 0.81; p less than 0.01). After testosterone therapy FSH plasma levels fall by 63 +/- 15% in all patients and did not show any important variation after naloxone infusion. In conclusion, our data are in agreement with the hypothesis that in Klinefelter's syndrome an alteration of opioid control on gonadotropin secretion may exist. This alteration does not appear to be due to androgen deficiency, but rather it may be caused by genetic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence of sperm nuclear chromatin heterogeneity in ex-cryptorchid subjects.

Ex-cryptorchid subjects are frequently affected by infertility, even if the usually determined seminal parameters are still within the normal range. We evaluated in this study, in 14 ex-unilateral cryptorchid adult males (22-28 years), with normal sperm concentration, morphology and viability, the resistance of sperm nuclear chromatin to denaturation, using the fluorochrome acridine orange, which fluorescences green when bound to native DNA (double stranded) and red when bound to denaturated DNA (single stranded). Our findings demonstrate that the percentage of green-stained cells with acridine orange was significantly lower in our patients than in controls (p less than 0.001). We therefore suggest that the chromatin of ex-cryptorchid subjects' spermatozoa has a decreased resistance to denaturation and we hypothesize that this finding may explain the infertility of these patients, when the common seminal parameters are still within the normal range.

Acridine Orange↗

Progesterone induces capacitation in human spermatozoa.

Mammalian sperm acrosome reaction is a prerequisite for oocyte fertilization, and to date the mechanisms regulating this event are still unclear. Recent studies have demonstrated that human follicular fluid is able to induce an influx of extracellular calcium and acrosome reaction in capacitated spermatozoa. More recently these effects have been attributed to progesterone. The results of our study demonstrated that progesterone is able to trigger the capacitation, acrosome reaction, and fertilizability in human spermatozoa through a calcium mediated mechanism, suggesting a clinical use of this steroid in the treatment of spermatozoa for the different techniques of assisted fertilization.

Acrosome↗