Naloxone has a Local Effect on the Testis of Immature Rats (original) (raw)
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Andrologia, 2009
The effect of simultaneous intratesticular injection of the opiate receptor antagonist naloxone and the neurotoxic drug 6-hydroxydopamine (6-OHDA) on testicular growth, compensatory testicular hypertrophy, serum testosterone level and basal testosterone secretion in vitro was studied in neonatal rats. In animals with two testes unilateral intratesticular administration of naloxone alone enhanced, while 6-OHDA alone decreased the weight of the treated gonad. In animals treated simultaneously with these two agents the decrease in testicular weight induced by 6-OHDA was partially prevented by naloxone. In hemicastrated animals intratesticular treatment with naloxone enhanced the extent of compensatory testicular hypertrophy. Treatment of the remaining testis with 6-OHDA + naloxone did not interfere with the diminished compensatory testicular hypertrophy observed following 6-OHDA treatment. Data indicate that naloxone can counteract the degenerative effect of 6-OHDA in animals with two testes but not in hemicastrates.
Local regulation of testicular immunoreactive-arginine vasopressin and steroidogenesis by naloxone
Biology of Reproduction, 1993
The effects of intratesticular injection of naloxone, a universal opioid antagonist, on testicular immunoreactive (IR)-arginine vasopressin (AVP) content and on in vitro testosterone production by Leydig cells were investigated in the mouse. Bilateral intratesticular injection of increasing doses of naloxone (0.1-10 pg/testis) resulted 24 h later in a dose-dependent increase in testosterone production by Leydig cells incubated for 3 h in the presence or absence of hCG (100 ng/ml). Unilateral intratesticular injection of naloxone (10 pg) similarly enhanced basal and hCG-stimulated testosterone production by Leydig cells, but production was not modified in Leydig cells from the contralateral vehicle-injected testis, nor was it changed when the same dose was injected subcutaneously. Unilateral intratesticular injection of 10 pg naloxone led to a dose-dependent increase in the hCG-responsiveness without altering the slope of the hCG dose-response curve. In vitro exposure of Leydig cells to increasing doses of naloxone (10-9 to 10-7 M) did not alter either basal or hCG-stimulated testosterone production. Testicular IR-AVP content declined in a dose-dependent manner in naloxone-injected testis, but remained unchanged in the contralateral vehicleinjected testis and in testis from animals that received similar doses of naloxone subcutaneously. Since AVP has been shown to locally exert a negative control on testosterone production within the testis, it might be hypothesized that the increased Leydig cell activity after local naloxone administration results from reduced intratesticular IR-AVP levels. The possibility that endogenous opioid peptides may locally control testosterone biosynthesis via testicular AVP system regulation is discussed.
Andrologia
The effect of simultaneous intratesticular injection of the opiate receptor antagonist naloxone and the neurotoxic drug 6-hydroxydopamine (6-OHDA) on testicular growth, compensatory testicular hypertrophy, serum testosterone level and basal testosterone secretion in vitro was studied in neonatal rats. In animals with two testes unilateral intratesticular administration of naloxone alone enhanced, while 6-OHDA alone decreased the weight of the treated gonad. In animals treated simultaneously with these two agents the decrease in testicular weight induced by 6-OHDA was partially prevented by naloxone. In hemicastrated animals intratesticular treatment with naloxone enhanced the extent of compensatory testicular hypertrophy. Treatment of the remaining testis with 6-OHDA + naloxone did not interfere with the diminished compensatory testicular hypertrophy observed following 6-OHDA treatment. Data indicate that naloxone can counteract the degenerative effect of 6-OHDA in animals with two testes but not in hemicastrates.
Comparative clinical pathology, 2011
The objective of the present work was to investigate the effects of buprenorphine administration on testicular tissue in mice. Sexually mature male mice were randomly divided into five experimental groups (n=5) and the following treatments were intraperitoneally administered for 21 days: Control male mice were given physiological saline. Positive control group was injected with morphine (Mor, 20 mg/kg). Three other groups were given different doses of buprenorphine including 0.15 mg/kg (B15), 0.30 mg/kg (B30), and 0.60 mg/kg (B60). Left testes were removed for histopathological evaluations and intracardiac blood samples were taken for testosterone assay. Morphometrically, the mean of seminiferous tubules diameter, spermatogonial cells diameter, sertoli cells diameter, and epithelial height were measured in the experimental groups. Meiotic index and the percentage of spermatogenesis were also calculated. The mean values of all of the above-mentioned parameters in the experimental groups showed significant decrease in comparison with the control group (p<0.05). No significant difference was observed between Mor and buprenorphine experimental groups except for the mean of germinal epithelium height which B60 showed significant reduction compared to Mor, B15, and B30 groups. Also, the effect of morphine on the reduction of spermatogenesis was similar to B30 group (p> 0.05), and in this regard, B60 group showed the most (56.36%) and B15 the least (76.16%) decrease in the mean percentage of spermatogenesis. The results show that buprenorphine could suppress plasma testosterone, damage spermatogenesis, and affect male fertility. Therefore, it should be used with attention for the treatment of opioid dependence.
The effect of naloxone on plasma concentrations of testosterone in male goats
The purpose of this work was to study the effect of the chronic administration of low doses of naloxone (0.5 mg/12 h/15 days) on plasma levels of testosterone in the anoestrus male goat. It was observed that during the first seven days of treatment, testosterone levels did not change. Thereafter, concentrations of testosterone increased to 7.5 + 0.3 ng/ml at the end of treatment. Following drug withdrawal, testosterone levels returned slowly to control values. It was concluded that the opioid antagonist, naloxone, administered in low doses, is capable of modifying testosterone concentrations in plasma, thereby giving further support that endogenous opioids are modulators of the reproductive function in goats.
Single opioid administration modifies gonadal steroids in both the CNS and plasma of male rats
Neuroscience, 2006
While morphine remains one of the most widely used opioids for the treatment of painful conditions, other opioids are also commonly employed. Because of the interactions between opioids and gonadal hormones, in particular opioid-induced hypogonadism, this study investigated the effects of widely used opioids on plasma testosterone and estradiol levels and brain testosterone levels in male rats. Animals were s.c. injected with two concentrations of morphine (5 or 10 mg/kg), fentanyl (0.05 or 0.1 mg/kg), tramadol (10 or 40 mg/kg), buprenorphine (0.05 or 0.1 mg/kg) or saline (0.7 ml/kg). Four or 24 h after treatment, the rats were deeply anesthetized to collect blood samples from the abdominal aorta and to perfuse the brains with saline. Plasma and brain hormone levels were measured by radioimmunoassay. In rats studied 4 h after treatment, all the opioids except tramadol 10 mg/kg decreased plasma testosterone in comparison with saline administration. At the same time, plasma estradiol levels were lower than control in the groups treated with the low doses of morphine, tramadol and buprenorphine, while estradiol remained at control levels in the other groups. Twentyfour hours after treatment, plasma testosterone levels were different (higher) than control in the animals treated with the low doses of morphine, fentanyl and buprenorphine. Estradiol was lower than control in the low dose groups, while the high doses did not produce any changes with respect to control. Four hours after treatment, brain testosterone was drastically decreased in all groups except buprenorphine, in which it remained at control levels. All groups returned to control levels at 24 h after treatment. In conclusion, opioids exert important effects on plasma and CNS sex hormone levels. The different magnitude and time-course of the effects of the different opiates on testosterone and estradiol levels are likely due to their different mechanism of action.
The role and regulation of testicular opioids
Trends in Endocrinology & Metabolism, 1990
Endogenous opioids are present in the male gonad and may be involved in the local control of testicular function. Testicular opioids are mainly produced in Leydig cells and exert direct paracrine inhibitory actions on the tubule, which in turn may have indirect Sertoli-cell-mediated effects on Leydig cell steroidogenesis. Gonadotropins and CRF stimulate production of gonadal opioids, and the presence of a gonadotropin milieu appears to be a requisite for the inhibitory paracrine actions of opioids on steroidogenesis. The recognition of such multiple intratesticular hormonal interactions should provide insights into the mechanisms involved in idiopathic infertility in men.
Background: Most studies on anabolic-androgenic steroids abuse have been done in adult rats, but few data are available to immature. Objective: This study was conducted to assay the effect of Nandrolone Decanoate (ND) on the testis and testosterone concentration in male immature rats compare with mature ones in short and long time. Materials and Methods: 40 mature rats were divided into 4 groups: group A (short term) and group B (long-term) received 10 mg/kg/day ND interaperitoneally for 35 and 70 days, respectively. Group C (control) without any treatment, and group D (vehicle) received dimethyl sulfoxide (DMSO) solution in two periods 35 and 70 days. 40 immature rats were divided into 4 groups same as mature ones. After surgery body weight, testis size, histomorphometry of testis, and serum testosterone level were evaluated. Results: Our results showed that ND decreased the number of Leydig cells in group B (39.9 ±. 919), group A (43.4 ±. 120), and long term (40.6 ±. 299) immature rats, which could result in a reduction of testosterone concentration significantly in all experimental groups except short term mature group. Number of sertoli cells, testis size, and diameter of seminiferous tubules decreased in the long-term immature group. Eventually, the number of sperm was decreased in mature and immature groups, but a severe depletion of sperm was occurred in both mature and immature in long time in comparison to the control group (p< 0.05). Conclusion: This time course study showed that supraphysiological dose of ND may negatively affect the number of Leydig cells, sperm cell, and testosterone concentration of immature rats in the same matter of mature rats. However, the number of sertoli cell, testis size, and seminferous diameter were decreased only in the long immature rats.
Journal of Interdisciplinary Histopathology, 2017
Objective: Frequently, reproductive toxic substances such as androgenic anabolic steroids, alcohol and nicotine are used in association by adolescents and adults, in an indiscriminate manner. This study investigated the testicular and epididymal tissue of adult rats submitted to a recovery period after treatment with anabolic steroid, alcohol and /or nicotine. Materials and Methods: The animals (n=42) were divided into three control groups simulating the drugs administration routes (CI: distilled water, oral; CII: saline solution, subcutaneous; CIII: water and saline solution) and groups treated with a testosterone esters mixture (T: 7.5 mg/kg body weight-b.w., subcutaneous), alcohol (AL: 3.5 g/kg b.w. of ethanol 25%, oral), nicotine (N: 2.0 mg/kg b.w., subcutaneous), and co-administration of these three substances (T/AL/N). After 15 consecutive days of treatment (once a day), the animals were kept for 30 days in recovery. At the end of this period, the testes and epididymides were collected, weighed and processed for histological and morphometric analysis by light microscope. Results: All groups treated with toxic substances presented histopathological changes in testes and epididymis after the recovery period. There was a significant decrease (p<0.05) in testicular weight and in the morphometric parameters of the testis and epididymis in T and T/AL/N groups. Conclusion: The testis and epididymis of rats treated with anabolic steroid, alcohol and/or nicotine exhibited histopathological changes after a recovery period and the damages were more evident in the groups receiving the anabolic steroid alone or co-administered with other drugs.
Reproduction, 1985
Methods have been established and validated for quantitative assessment of the distribution of testosterone in the testis, by measurement of testosterone concentrations in whole testis, in isolated seminiferous tubules and in testicular interstitial fluid. These measurements were made in individual rats injected 2\p=n-\40h previously with saline (0\m=.\9%NaCl) or a potent antiserum to ovine LH. Testosterone concentrations in interstitial fluid and seminiferous tubules were closely correlated (r = +0\m=.\98; n = 60) and their relationship was log linear over a 200-fold range. However, although the concentrations of testosterone in interstitial fluid and seminiferous tubules decreased progressively with time after LH antiserum injection, this decrease was far more pronounced for interstitial fluid. In association with this change there was a significant increase in the amounts of a locally-produced factor in interstitial fluid which stimulates basal and hCG-stimulated testosterone production by isolated purified Leydig cells. This increase was reversed by injection of hCG but not by peripheral injection of a dose (20 mg) of testosterone propionate which restored normal intratesticular concentrations of testosterone. It is concluded that the tubular 'conservation' of testosterone, which occurs as interstitial fluid levels of this steroid decrease, may be a consequence of restricted diffusion of testosterone out of the tubules, but is also associated with increased amounts of a peptide stimulator of testosterone production. would provide further insight into the local control of intratesticular testosterone levels, as well as providing basic information on how testosterone is normally distributed between these two compartments. Materials and Methods Animals, treatments and collection of tissues. Sprague-Dawley rats aged 75-90 days from our own colony were used for all experiments and were housed under conventional conditions. Four experiments were undertaken initially to validate the procedures used in this study. Experiment 1 was performed to establish the accuracy of the methods used for measurement of testosterone concentrations in testicular interstitial fluid. Groups of rats were injected subcutaneously with 0-7 ml 0-9% (w/v) NaCl (controls), 10 pg ovine LH (NIH-LH-S24) in 0-7 ml 0-9% NaCl or 0-7 ml of a highly potent rabbit antiserum to ovine LH (R-31), and killed 2 or 5 h later. Characteristics of the LH antiserum have been described elsewhere (Sharpe & Fraser, 1983). In addition to these treatments each rat had received an earlier subcutaneous injection of 5 106 c.p.m. ' 25I-labelled bovine serum albumin (BSA, fraction V : Sigma, St Louis, MO, U.S.A.) in 0-2 ml 0-9% NaCl, this treatment being given 8 h before the animals were killed to allow equilibration of the levels of radiolabelled BSA in serum and testicular interstitial fluid (Setchell & Sharpe, 1981; Sharpe & Cooper, 1983). Animals were killed with solid C02-generated C02, and blood was collected from * < 0001, compared with respective control group (Student's t test). t Assuming 1240 cm tubule/g testis (Wing & Christensen, 1982). i Assuming that IF accounts for 12-5% of testicular weight (derived from the study illustrated in Table 1).