Adrenocorticotropin administration increases testosterone secretion in adult male rats

It appears that the effect of acute administration of pituitary-adrenal hormones on the pituitary-gonadal axis is species-dependent. However, no information is available with regard to the effect of acute adrenocorticotropin (ACTH) administration on testosterone secretion in rats. The present data indicate that acute ACTH administration can increase serum testosterone levels without modifying luteinizing hormone (LH) levels. Since this rise was not observed in castrated rats, it must be assumed that increased serum testosterone was of gonadal origin. The action of ACTH on testosterone secretion was likely an indirect one since there is no evidence at present for a direct, short-term action of the pituitary-adrenal axis on Leydig cell function.     

Effects of oral administration of nicotine on organ weight, serum testosterone level and testicular histology in adult male rats

This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0 mg/kg (high dose) body weight of nicotine while the control rats received 0.2 ml/kg normal saline. The fourth and fifth groups were gavaged with 0.5mg/kg and 1.0mg/kg body weight of nicotine but were left untreated for another 30 days. These groups served as the recovery groups.  At the end of each experimental period, the animals were scarified and their reproductive organs were removed and weighed immediately. There was no significant change in the body weight. There was a significant decrease (p <0.05) in the testicular and epididymal weight of rats for both treatments while the decrease in the seminal vesicle weight for both treatment groups was not significant. The prostate weight was not significantly increased in both groups. The recovery groups showed appreciable recovery in their organ weight. Serum level of testosterone of both groups was significantly decreased in a dose dependent manner when compared with those of the control rats. The histological section showed testicular degeneration and disorganization in the cytoarchitecture, as the observed changes were pronounced in the high dose group than the low dose group. However, there were both regeneration of the germinal epithelium and restructuring of the interstitum towards normal in the recovery groups. No lesion was observed in the epididymis of the rats. The results suggest that nicotine has deleterious effect on the male reproductive organ of albino rats ameliorated by nicotine cessation.     

Chronic crude garlic-feeding modified adult male rat testicular markers: mechanisms of action

Background  

Garlic or Allium sativum (As) shows therapeutic effects such as reduction of blood pressure or hypercholesterolemia but side-effects on reproductive functions remain poorly investigated. Because of garlic's chemical complexity, the processing methods and yield in preparations differ in efficacy and safety. In this context, we clarify the mechanisms of action of crushed crude garlic on testicular markers.     

Effect of sodium molybdate on cadmium-related testicular damage in adult male Wistar rats

BackgroundMolybdenum, as a trace element, has various pharmacological effects, including antioxidant, antiviral, anti-allergic, anti-osteoporosis, anti-tumor, anti-inflammatory, anti-diabetic, anti-obesity, and free radical-scavenging activities. This study aimed at investigating the sodium molybdate impacts on cadmium chloride (CdCl₂)-induced testicular toxicity in adult Wistar rats.MethodsThe impacts of oral administration of sodium molybdate (0.05, 0.1, 0.2, and 0.4 mg/kg) was evaluated in healthy and infertile animals. Animals were randomly assigned to nine groups, including healthy control, sodium molybdate alone, infertile control (3 mg/kg of CdCl₂), and sodium molybdate plus CdCl₂. Following 30 days of administration, animals were sacrificed for biochemical and histopathological assays.ResultsThe results indicated that administration of sodium molybdate to infertile rats significantly mitigated the cadmium impacts on sperm appearance, concentration, and motility parameters. Also, sodium molybdate reduced the production of malondialdehyde (MDA) and enhanced antioxidant enzymes activities in the testicular homogenates in rats; these findings were supported by histopathological examinations. Treatment with sodium molybdate significantly increased aquaporin-9 (AQP9) expression in the testicular tissues of infertile rats.ConclusionsThe current findings suggested that sodium molybdate performs as a strong protective agent from CdCl₂-related testicular toxicity in rats.     

Suppression of testicular maturation and fertility following androgen administration to neonatal male rats

Administration of supraphysiologic doses of androgen to male rats within the first few neonatal days markedly suppresses subsequent testicular maturation; this effect diminishes as androgen is injected on succeeding postnatal days. Testosterone propionate (TP) administered neonatally at dosages up to 3.5 mg appreciably diminished postnatal testicular growth; postpubertal androgen secretion, as assessed by accessory sex organ weights and serum testosterone concentrations and as reflected by a castrationlike developmental pattern of the hepatic enzyme, histidase; spermatogenesis; and fertility. Beyond three mo of age testicular growth rates and androgen secretion--but not fertility--tended to be restored. These effects of neonatal androgen do not require aromatization to estrogen; indeed 5 alpha-dihydrotestosterone elicited more profound testicular suppression than TP, which was sustained until at least 100 days of age. Testes of neonatally androgenized rats were capable of responding to gonadotropins administered at three wk of age with increases in weight and androgen secretion. These findings suggest that a developmental event, suppressible by pharmacologic doses of androgen, occurs at a nontesticular site during the first few post partum days in the male rat; this event programs subsequent testicular maturation.     

Galanin stimulates hCG induced testicular steroidogenesis in adult but not in immature male rats

The present study was undertaken to understand the role of galanin on testosterone secretion. Leydig cells from adult (60-80 days old) and immature (21-30 days old) rat testis were incubated with galanin (100 nM), galantide (100 nM) and Human Chorionic Gonadotropin (hCG, 25 I.U.) alone or in combinations and testosterone release was measured. It was observed that in adults, galanin failed to alter the basal testosterone release from the dispersed Leydig cells but potentiated the hCG induced testosterone release significantly. While galantide, prevented this galanin potentiating effect, but it did not alter the hCG alone induced testosterone release. On the other hand, the Leydig cells obtained from immature male rats were sensitive to hCG alone but not to galanin or galantide, both of which failed to alter the hCG induced testosterone release from these cells. Based on these results it can be postulated that galanin's role at the level of the male gonad is age dependent since its potentiating effects on hCG induced testosterone release were visible only in the adult and not in the immature male rats.     

Role of glucocorticoids in the stress-induced suppression of testicular steroidogenesis in adult male rats.

We have examined the role of glucocorticoids in the stress-induced inhibition of testicular steroidogenesis. Immobilization (3 hr) reduced plasma testosterone (T) levels to 24% of control values but did not affect plasma LH levels. This reduction was partially reversed by in vivo injections of the antiglucocorticoid, RU486, prior to the stress session at a dose of 10 mg/kg BW, but not at 1.0 or 50 mg/kg BW. Stressed rats that were treated with 10 mg/kg BW RU486 had twofold higher plasma T levels than vehicle-treated stressed animals. Injections of RU486 did not affect plasma LH levels in control or stressed rats and did not affect T levels of unstressed rats. Stressed rats had eightfold higher plasma corticosterone levels than controls, and RU486 had no effect on control or stress levels of corticosterone. The possible role of glucocorticoids in mediating the effect of stress on testicular T production was investigated also in vitro by incubating testicular interstitial cells from unstressed rats for 3 hr with corticosterone (0, 0.01, 0.1, or 1.0 microM) or dexamethasone (0, 0.001, 0.01, or 0.1 microM), followed by an additional 2 hr with hCG (0, 25, 50, or 100 microIU). Both corticosterone and dexamethasone inhibited hCG-stimulated T production in a dose-dependent manner. Cells incubated with the highest concentration of either of the glucocorticoids showed significantly reduced responses to hCG stimulation. In the absence of hCG, in vitro T production was not affected by dexamethasone or 0.01 and 0.1 microM corticosterone. However, the highest dose of corticosterone (1.0 microM) produced a 63% elevation in basal T production. Coincubation of testicular interstitial cells with corticosterone (1.0 microM) or dexamethasone (0.1 microM) and RU486 (0.01, 0.1, and 1.0 microM) reversed the glucocorticoid-induced suppressions of T production in a dose-dependent manner. Our results suggest that during stress increases in plasma levels of glucocorticoids in male rats act via glucocorticoid receptors on testicular interstitial cells to suppress the testicular response to gonadotropins, and that the decline of testosterone production during immobilization stress is in part mediated by a direct action of glucocorticoids on the testis.     

The role of testicular hormones and luteinizing hormone in spatial memory in adult male rats

Attempts to determine the influence of testicular hormones on learning and memory in males have yielded contradictory results. The present studies examined whether testicular hormones are important for maximal levels of spatial memory in young adult male rats. To minimize any effect of stress, we used the Object Location Task which is a spatial working memory task that does not involve food or water deprivation or aversive stimuli for motivation. In Experiment 1 sham gonadectomized male rats demonstrated robust spatial memory, but gonadectomized males showed diminished spatial memory. In Experiment 2 subcutaneous testosterone (T) capsules restored spatial memory performance in gonadectomized male rats, while rats with blank capsules demonstrated compromised spatial memory. In Experiment 3, gonadectomized male rats implanted with blank capsules again showed compromised spatial memory, while those with T, dihydrotestosterone (DHT), or estradiol (E) capsules demonstrated robust spatial memory, indicating that T's effects may be mediated by its conversion to E or to DHT. Gonadectomized male rats injected with Antide, a gonadotropin-releasing hormone receptor antagonist which lowers luteinizing hormone levels, also demonstrated spatial memory, comparable to that shown by T-, E-, or DHT-treated males. These data indicate that testicular androgens are important for maximal levels of spatial working memory in male rats, that testosterone may be converted to E and/or DHT to exert its effects, and that some of the effects of these steroid hormones may occur via negative feedback effects on LH.     

Adolescent TBI‐induced hypopituitarism causes sexual dysfunction in adult male rats

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI‐induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long‐term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI‐induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 193–202, 2015     

Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats

Effects of a xenobiotic estrogen, bisphenol A (BPA), on reproductive functions were investigated using adult male rats. BPA was dissolved into sesame oil and injected s.c. every day (1 mg/rat) for 14 days. Animals were killed by decapitation after the final administration of BPA, and the trunk blood, pituitary, and testes were collected. Plasma concentrations of prolactin were dramatically increased and pituitary contents of prolactin were slightly increased in the BPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased in BPA-treated rats compared to control rats. Testicular contents of inhibin were decreased in BPA-treated rats compared to control rats, although plasma concentrations of inhibin were not changed after administration of BPA. The testicular response to hCG for progesterone and testosterone release was decreased in BPA-treated rats. Administration of BPA did not change the pituitary response to luteinizing hormone-releasing hormone (LH-RH) in castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of BPA treatment. These results suggest that BPA directly inhibits testicular functions and the increased level of plasma LH is probably due to a reduction in the negative feedback regulation by testosterone. The testis is probably a more sensitive site for BPA action than the hypothalamus-pituitary axis.     

Piperine activates testicular apoptosis in adult rats

Piperine, an alkaloid present in the fruits of commonly used spice pepper, is known to impair reproductive functions. In the present study, piperine was administered to adult male rats at the dose levels of 1, 10, and 100 mg/kg body weight for 30 days to evaluate its effects on the testis. A significant decrease in the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the testis was observed at 10 and 100 mg of piperine administration when compared with the controls. A dose‐dependent increase in lipid peroxidation and hydrogen peroxide generation was also observed. Sialic acid levels in the testis were also found to be decreased when piperine was administered at 10 and 100 mg dose levels. Immunofluorescence studies demonstrated a dose‐dependent increase in caspase 3 and Fas protein in testicular germ cells after piperine treatment. These observations indicate that piperine induces oxidative stress and thereby triggers apoptosis in the testis, contributing to hampered reproductive functions. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:382–388, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20251     

Gossypol and testicular lipids of adult rats

Testicular lipids act as source of energy, structural components of spermatozoa and precursors of androgen biosynthesis. Treatment with antispermatogeneic agents cause accumulation of testicular lipids. Gossypol, an effective antispermatogenic agent causes marked accumulation of testicular neutral lipids. It did not affect testicular phospholipids. Gossypol treatment did not bring about marked changes in the key enzymes like HMG Co A reductase, glucose-6-phosphate dehydrogenase malic enzyme and cytosolic isocitrate dehydrogenase involved in sterol biosynthesis. Thus, gossypol brings about marked accumulation of glycerides and esterified cholesterol in the testis due to its effect on spermatogenic elements of adult rats.     

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

Background

Hyperglycemia can impair the male reproductive system in experimental animals and in men during reproductive age. Studies have shown that vitamin C has some good effects on male reproductive system, and therefore vitamin C treatment could attenuate the dysfunctions in this system caused by hyperglycemia. Thus, the objective of this work was to evaluate whether vitamin C treatment could attenuate reproductive dysfunctions in hyperglycemic male rats.

Methods

Adult male rats were divided into 3 groups: a normoglycemic (n = 10) and two hyperglycemic (that received a single dose of streptozotocin - 40 mg/kg BW). The two last groups (n = 10 per group) were divided into: hyperglycemic control (Hy) and hyperglycemic + 150 mg of vitamin C (HyC), by gavage during 30 consecutive days. The normoglycemic and hyperglycemic control groups received the vehicle (water). The first day after the treatment, the rats were anesthetized and killed to evaluate oxidative stress biomarkers (TBARS, SOD, GSHt and GSH-Px) in the erythrocytes, body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology.

Results

Compared with the normoglycemic animals, hyperglycemic control rats showed reduced weight of the body and reproductive organ but testis weight was maintained. It was also observed reduction of testosterone and LH levels, seminiferous tubular diameter, sperm motility and sperm counts in the epididymis. In addition, there was an increase in morphological abnormalities on spermatozoa as well as in oxidative stress level. Vitamin C reduced the oxidative stress level, diminished the number of abnormal sperm, and increased testosterone and LH levels and seminiferous tubular diameter but did not show improvement of sperm motility in relation to the hyperglycemic control group. Hyperglycemia caused a rearrangement in the epididymal tissue components (stroma, ephitelium and lumen) as demonstrated by the stereological analysis results. However, this alteration was partially prevented by vitamin C treatment.

Conclusions

We conclude that vitamin C partially attenuated some male reproductive system dysfunctions in hyperglycemic rats.     

Infertility and testicular atrophy in the antiestrogen-treated adult male rat

The estrogen receptor-alpha (ERalpha) knockout mouse (alphaERKO) lacks ERalpha throughout development; therefore, an adult model for the study of estrogen effects in male mice was recently developed using the antiestrogen ICI 182,780. However, differences between species have been noted during immunostaining for ERalpha in the male tract as well as in response to treatments with antiestrogens. Therefore, we developed the antiestrogen model in the adult male rat to test, in another species, the hypothesis that estrogen regulates fluid reabsorption in efferent ductules. Estrogen receptor in the rat was blocked using ICI 182,780 for 100-150 days. Male Sprague-Dawley rats were treated weekly with s.c. injections of ICI 182,780 (10 mg) or castor oil (as control). The effects of ICI included testicular atrophy and infertility, similar to terminal effects in the alphaERKO male. Additionally, ICI induced dilations of the rete testis and efferent ductules and a reduction in the height of the ductule epithelium, which are changes similar to those in both alphaERKO and ICI-treated mice. One difference between species was a large variation in effects on the rat efferent ductule epithelium, including a transient increase in the number of periodic acid-Schiff-positive, lysosomal-like granules. These data confirm that estrogen is required for normal function of the efferent ductules and is essential for long-term fertility in the male rodent.     

Peri-pubertal exposure to testicular hormones organizes response to novel environments and social behaviour in adult male rats

Previous research has shown that exposure to testicular hormones during the peri-pubertal period of life has long-term, organizational effects on adult sexual behaviour and underlying neural mechanisms in laboratory rodents. However, the organizational effects of peri-pubertal testicular hormones on other aspects of behaviour and brain function are less well understood. Here, we investigated the effects of manipulating peri-pubertal testicular hormone exposure on later behavioural responses to novel environments and on hormone receptors in various brain regions that are involved in response to novelty. Male rodents generally spend less time in the exposed areas of novel environments than females, and this sex difference emerges during the peri-pubertal period. Male Lister-hooded rats (Rattus norvegicus) were castrated either before puberty or after puberty, then tested in three novel environments (elevated plus-maze, light–dark box, open field) and in an object/social novelty task in adulthood. Androgen receptor (AR), oestrogen receptor (ER1) and corticotropin-releasing factor receptor (CRF-R2) mRNA expression were quantified in the hypothalamus, hippocampus and medial amygdala. The results showed that pre-pubertally castrated males spent more time in the exposed areas of the elevated-plus maze and light–dark box than post-pubertally castrated males, and also confirmed that peri-pubertal hormone exposure influences later response to an opposite-sex conspecific. Hormone receptor gene expression levels did not differ between pre-pubertally and post-pubertally castrated males in any of the brain regions examined. This study therefore demonstrates that testicular hormone exposure during the peri-pubertal period masculinizes later response to novel environments, although the neural mechanisms remain to be fully elucidated.     

Influence of melatonin on the testicular regression induced by subcutaneous testosterone pellets in male rats kept in long or short photoperiod

Daily afternoon injections of 25 micrograms melatonin for 12 weeks had no effect on testicular weights of male rats kept in long photoperiod (14L:10D); similarly, exposure of rats to short photoperiod (2L:22D) had no effect on gonadal weight. However, rats maintained in a long or short photoperiod and implanted every 2 weeks with a 15 mm Silastic pellet containing testosterone showed a significant reduction in testicular weight; this effect was more pronounced in rats exposed to a short photoperiod. Melatonin injections in testosterone-treated rats in a long photoperiod exacerbated the inhibitory effects of testosterone alone. Subcutaneous 2-weekly implants of a beeswax pellet containing 1 mg melatonin reversed the effects of the melatonin injections on relative testicular weights but not those due to short photoperiod exposure. Testosterone implants significantly reduced pituitary LH values in long and short photoperiod-exposed animals, more particularly in those exposed to short photoperiod. Melatonin injections alone or in combination with melatonin pellets did not further exaggerate the depression in pituitary LH due to testosterone alone in long photoperiod-exposed animals; similarly melatonin pellets did not reverse the depression in pituitary LH observed. No significant differences in plasma prolactin concentrations or in thyroxine concentrations or free thyroxine index were observed after any combination of treatments. We therefore suggest that the effects observed with short photoperiod may be due to melatonin.     

In vivo metabolism of 3H-testosterone in adult male rats: effects of estrogen administration.

The metabolism of testosterone (T) was studied in normal adult male rats using a constant infusion of trace amounts of the 3H-steroid into a tail vein for 3 h in order to attain a state of equilibrium. Samples of plasma, liver, kidney, prostate, seminal vesicles and muscle were analysed for 3H-testosterone, 3H-5alpha-dihydrotestosterone (5alphaDHT) and 3H-5alpha-androstanediol (Adiol). When compared to the 3H-T level in plasma there were high levels of 3H-T in kidney and of 3H-5alphaDHT in prostate and seminal vesicles. Intraperitoneal estradiol valerate administration (100 mug/day) for 4 days decreased and 3H-5alphaDHT levels in the prostate and seminal vesicles. The estrogen administration increased the T metabolic clearance rate from 17.5 1/24 h/100 g body wt to 22.6 1/24 h/100 g body wt.     

Chronic enhancement of brain oxytocin levels causes enduring anti-aggressive and pro-social explorative behavioral effects in male rats

Oxytocin (OXT) has been implicated in the regulation of social behaviors, including intermale offensive aggression. Recently, we showed that acute enhancement of brain OXT levels markedly suppressed offensive aggression and increased social exploration in resident rats confronted with an intruder in their home territory. Moreover, a different responsivity to the exogenous OXTergic manipulation was observed among individuals based on their baseline aggression. In this study we aimed at evaluating the behavioral response to chronically enhancing or attenuating central OXT levels, and at scrutinizing whether the trait-aggression moderates the treatment-induced behavioral changes. To this end, resident male wild-type Groningen rats were continuously (via osmotic minipumps) intracerebroventricularly infused with synthetic OXT or a selective OXT receptor (OXTR) antagonist for 7 days. Changes in behavior were assessed performing a resident–intruder test before and at the end of the treatment period, as well as after 7 days of withdrawal. Chronic infusion of OXT was found to selectively suppress aggression and enhance social exploration. Chronic blockage of OXTRs instead increased introductory aggressive behavior (i.e. lateral threat), yet without affecting the total duration of the aggression. The magnitude of the anti-aggressive changes correlated positively with the level of baseline aggression. Interestingly, OXT-induced behavioral changes persisted 7 days after cessation of the treatment. In conclusion, these findings provide further evidence that enhanced functional activity of the central OXTergic system decreases social offensive aggression while it increases social explorative behavior. The data also indicate that chronically enhancing brain OXT levels may cause enduring anti-aggressive and pro-social explorative behavioral effects.