Testosterone In Male Rats Research Articles

The relationship between the levels of melatonin and testosterone in male rats of different ages with ulcer of the stomach

Seasonality and dependence of age and sex is an important question in the development of ulcer of the stomach. Melatonin has an important place among the hormones that are involved in the formation of ulcer of the gastric mucosa.Aim. In order to establish the relationship between the levels of melatonin and testosterone in ulcerative lesions of the stomach in male rats of different ages their level in the blood serum was studied by enzyme immunoassay ELISA.Methods and results. It was found that against the background of gastric ulceration a significant increase in melatonin levels and decrease in serum testosterone occur, most expressed in rats aged 9 months.Conclusion. The obtained results indicate the presence of the relationship between melatonin and testosterone levels in both normal and pathological conditions.

The Effect of Intraventricular Administration of Zinc on Serum LH, FSH, Prolactin, and Testosterone in Male Rats

Background: Zn is calcium channels blocker and interferes with biological function of calcium ion, and FSH and LH secretion are dependent on calcium ion. Objectives: The aim of this study was evaluate the effects of supra physiological dose of zinc injection in lateral ventricle (LV) on serum FSH, LH, testosterone, and prolactin (PRL) in male rats. Materials and Methods: This experiment was performed on 30 Wistar-Albino male rats weighing 220 - 260 g, which were cannulated in LV. Rats were divided into: sham control (SC), control (V), and test (T) groups, randomly. Test group received 10 µL of artificial cerebra spinal fluid (ACSF) containing 0.06 μmol zinc sulfate, for 20 days. Group V was given the same volume of ACSF, but group SC did not receive any agent at this time. At the end, animals were anesthetized by diethyl ether, sacrificed and blood samples were collected. Serum gonadotropins and prolactin were measured via rat kits and ELISA methods. Testosterone was measured by ordinary methods. Obtained data were analyzed by SPSS-17 software and Kruskal-Wallis, Mann-Whitney and Bonnferoni correction statistical tests. Results were expressed as mean ± SD. Statistical differences were recognized significant at P < 0.05. Results: Our findings showed that serum LH, food and weight gain in group T significantly decreased but prolactin value in this group increased in comparison to those in other groups. Conclusions: We conclude that intraventricular (IV) injection of supra physiological dose of zinc sulfate in IV affected on serum LH, prolactin, food intake, and gain of weight in male rats.

Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats

Although sex steroids are known to modulate brain dopamine, it is still unclear how testosterone modifies locomotor behaviour controlled, at least in part, by striatal dopamine in adolescent males. Our previous work suggests that increasing testosterone during adolescence may bias midbrain neurons to synthesise more dopamine. We hypothesised that baseline and amphetamine-induced locomotion would differ in adult males depending on testosterone exposure during adolescence. We hypothesised that concomitant stimulation of estrogen receptor signaling, through a selective estrogen receptor modulator (SERM), raloxifene, can counter testosterone effects on locomotion.Male Sprague-Dawley rats at postnatal day 45 were gonadectomised (G) or sham-operated (S) prior to the typical adolescent testosterone increase. Gonadectomised rats were either given testosterone replacement (T) or blank implants (B) for six weeks and sham-operated (i.e. intact or endogenous testosterone group) were given blank implants. Subgroups of sham-operated, gonadectomised and gonadectomised/testosterone-replaced rats were treated with raloxifene (R, 5mg/kg) or vehicle (V), daily for the final four weeks. There were six groups (SBV, GBV, GTV, SBR, GBR, GTR). Saline and amphetamine-induced (1.25mg/kg) locomotion in the open field was measured at PND85.Gonadectomy increased amphetamine-induced locomotion compared to rats with endogenous or with exogenous testosterone. Raloxifene increased amphetamine-induced locomotion in rats with either endogenous or exogenous testosterone. Amphetamine-induced locomotion was negatively correlated with testosterone and this relationship was abolished by raloxifene.Lack of testosterone during adolescence potentiates and testosterone exposure during adolescence attenuates amphetamine-induced locomotion. Treatment with raloxifene appears to potentiate amphetamine-induced locomotion and to have an opposite effect to that of testosterone in male rats.

Sexual behavior attenuates the effects of chronic stress in body weight, testes, sexual accessory glands, and plasma testosterone in male rats

The aim of this study was to evaluate whether continuous sexual behavior could attenuate the effects of chronic stress on spermatogenesis, sexual glands, plasma testosterone and corticosterone in sexually experienced male rats. Rats were exposed to stress by immersion in cold water (ICW) daily for 20 or 50 consecutive days. Plasma testosterone and corticosterone, masculine sexual behavior, as well as the number of offspring, the epithelial area of seminiferous, prostatic and seminal glands were assessed. In stressed males, body and testicular weights decreased, male sexual behavior was disrupted, and adrenal weights increased. In males stressed for 50days, prostate and seminal glands had lower weights compared with controls. Prostate and seminal epithelial areas also decreased in these males. Seminiferous tubules in testes from rats stressed for 20 or 50days showed several degenerative signs, such as vacuoles in the basal epithelium, with picnotic indicia; moderate to severe exfoliation of degenerative germinal cells in the tubule lumen was also observed. In males stressed for 50days a significant decrease in seminiferous epithelial area was observed from stages I–VIII, regardless of copulation. The litters from females that copulated with males stressed for 50days decreased significantly. Chronic stress caused increase in plasma levels of corticosterone, which were higher in males stressed for 20days than in males stressed for 50days. Testosterone decreased in stressed males and it was lower in males stressed for 50days. In stressed males allowed to copulate, body and testicular weights were similar to controls. Adrenal, seminal glands, and prostate weights, as well as epithelial areas of males stressed for 50days allowed to copulate were also similar to controls. Corticosterone was lower than in males stressed for 50days, but still higher than in controls. Testosterone in males stressed for 50days and allowed to copulate was higher than in stressed males not allowed to copulate and control males without copulation, but still lower than in control copulating males. These results show that chronic stress causes germ cell loss in testes and a decrease in prostate and seminal epithelium, possibly as a result of testosterone decrease, affecting fertility. Continuous copulation can attenuate the effects of stress on testosterone levels and on the epithelial area in male sexual glands, but not on the seminiferous epithelium after 50days of stress.

The effects of orchidectomy on toxicological responses to dietary ochratoxin A in Wistar rats

Ochratoxin A (OTA) causes pathological lesions in the organs of animals. Males are more sensitive to OTA exposure than females but the reasons for this are unknown.The objective of this study was to explore the role of testosterone in male rats with OTA-related pathogenesis. To test the effect of testosterone on OTA toxicity, the testes of a group of rats were surgically removed. Male and female rats (approximately 300 and 200g) were fed with OTA-contaminated feed (initially approximately 300μgkg−1 b.w. per day) for 24 weeks. The organs of all the animals were collected and their organ lesion pathology, caspase-3 expression, OTA plasma and organ concentrations and total plasma testosterone concentrations were evaluated. OTA treatment created serious lesions in the kidney, liver and testes of rats. The major histopathological changes in the kidney and liver were karyomegaly, hemorrhages and vacuolization. In the testes, there was a marked decrease in the amount of spermatozoon. The degrees of organ lesion were evaluated and the castrated males had the lowest kidney and liver lesion scores, indicating that testosterone reduction in males dramatically reduces OTA-related organ damage. The plasma OTA levels for the intact males, the castrated and the females were 6.34, 8.42 and 12.5μgml−1, respectively.In conclusion, despite the similar plasma OTA levels of the intact and castrated males, OTA is less toxic in the castrated males. Therefore, the well-known gender specific toxicity of OTA seems to be related to the testosterone levels of rats.

Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide

Kisspeptin/metastin, a hypothalamic peptide, plays a pivotal role in controlling gonadotropin-releasing hormone (GnRH) neurons, and we have shown that continuous subcutaneous administration of kisspeptin analogues suppresses plasma testosterone in male rats. This study examined pharmacologic profiles of investigational kisspeptin analogues, TAK-448 and TAK-683, in male rats. Both analogues showed high receptor-binding affinity and potent and full agonistic activity for rat KISS1R, which were comparable to natural peptide Kp-10. A daily subcutaneous injection of TAK-448 and TAK-683 (0.008–8μmol/kg) for consecutive 7 days initially induced an increase in plasma luteinizing hormone and testosterone levels; however, after day 7, plasma hormone levels and genital organ weights were reduced. Continuous subcutaneous administrations of TAK-448 (≥10pmol/h, ca. 0.7nmol/kg/day) and TAK-683 (≥30pmol/h, ca. 2.1nmol/kg/day) induced a transient increase in plasma testosterone, followed by abrupt reduction of plasma testosterone to castrate levels within 3–7 days. This profound testosterone-lowering effect was sustained throughout 4-week dosing periods. At those dose levels, the weights of the prostate and seminal vesicles were reduced to castrate levels. These suppressive effects of kisspeptin analogues were more rapid and profound than those induced by the GnRH agonist analogue leuprolide treatment. In addition, TAK-683 reduced plasma prostate specific antigen (PSA) in the JDCaP androgen-dependent prostate cancer rat model. Thus, chronic administration of kisspeptin analogues may hold promise as a novel therapeutic approach for suppressing reproductive functions and hormone-related diseases such as prostate cancer. Further studies are warranted to elucidate clinical significance of TAK-448 and TAK-683.

Testosterone Changes Bladder and Kidney Structure in Juvenile Male Rats

Testosterone affects male development, maturation and aging but limited data exist on testosterone effects on the juvenile genitourinary system. We hypothesized that testosterone has bladder and kidney developmental effects, and investigated this in juvenile male rats. To examine the testosterone effect 21-day-old prepubertal male Wistar rats were divided into 3 groups of 12 each, including sham orchiectomy as controls, and bilateral orchiectomy with vehicle and bilateral orchiectomy with testosterone. Starting at age 28 days (week 0) testosterone enanthate (5 mg/100 gm) or vehicle was injected weekly. Testosterone was measured at study week 0 before injection, and at weeks 1, 6 and 16. Whole bladders and kidneys were evaluated for androgen receptor, bladder collagen-to-smooth muscle ratio, and renal morphometry and immunohistochemistry. Testosterone was not detectable at week 0 in all groups. It remained undetectable at weeks 1, 6 and 16 in the orchiectomy plus vehicle group. Testosterone levels were physiological in controls and rats with orchiectomy plus testosterone but levels were higher in the latter than in the former group. Rats with orchiectomy plus testosterone had increased bladder-to-body and kidney-to-body weight ratios (p<0.01 and <0.05, respectively), and decreased collagen-to-smooth muscle ratio than the orchiectomy plus vehicle and control groups. Rats with orchiectomy plus testosterone had a lower renal total glomerular count (p<0.01) but increased androgen receptor density. In juvenile male rats testosterone was associated with increased bladder and renal mass, and increased bladder smooth muscle. Testosterone associated kidneys also appeared to have fewer but larger glomeruli. These data support an important role for sex hormones in structural and functional development of the bladder and kidney.

Effect of Gonadal hormones on hypophagic property of Opioid antagonist naloxone

Background: Studies have shown that hormonal fluctuations that occur over the estrous cycle in rats affect food intake. It is possible that estrogen affects food intake via Opioid system and other brain areas which are involved in regulation of food intake. Therefore it may affect the sensitivity of female rats to hypophagic effect of Opioid antagonist Naloxone. Testosterone in male rats also changes food intake. However, little is known about hoe these Gonadal hormones interact with Opioid receptors to modulate food intake. Objective: The aim of the study was to find out how Gonadal hormones affect hypophagic property of Naloxone. Methods: Basal food intake of 40 healthy adult females and 20 healthy adult male rats was recorded. Then they were injected intraperitoneally with Naloxone after fasting for 24 hrs. In female rats food intake was measured during different phases of the estrous cycle. All the rats were then subjected to gonadectomy. The food intake was measured after gonadectomy. The effect of Naloxone was also measured in deprivation paradigm after gonadectomy. Results: Female rats showed decreased food intake during proestrous and estrous phases. In female rats there was no hypophagia after Naloxone injection during these phases. Male rats showed hypophagia on Naloxone injection. Male rats showed increased food intake after gonadectomy. In female rats the increase in food intake was not significant when gonadectomy was done during metestrous and diestrous. However, Naloxone could induce hypophagia in all female rats after gonadectomy. Conclusion: Estrogen decreases food intake, it decreases sensitivity of female rats to hypophasic effects of Naloxone. Testosterone decreases food intake. Testosterone does not interfere with hypophagic effect of Naloxone.

Relationship between 22-kHz calls and testosterone in male rats

Ultrasonic calls in rats induced by the presence of a predator, referred to as “22-kHz calls,” are mainly emitted by socially dominant male rats. Testosterone levels are closely related to social dominance in male rats. In the present study, we investigated the relationship between the emission of stress-induced 22-kHz calls and circulating testosterone levels in male rats, using a combination of surgery (castration or sham operation) and chronic steroid administration (testosterone or cholesterol) to modify circulating testosterone levels. We also assessed the effects of androgen and/or estrogen receptor antagonists on the emission of 22-kHz calls in male rats. An air puff stimulus, known to reliably induce 22-kHz calls in rats, was used as a stressor. Castrated rats with cholesterol implants exhibited significantly fewer 22-kHz calls than rats that had received a sham operation and cholesterol implants, and there was no significant difference between castrated rats with testosterone implants and rats that had received a sham operation and cholesterol implants. Only male rats pretreated with a binary mixture of androgen and estrogen antagonists exhibited significantly fewer 22-kHz calls than controls. These results show that testosterone in male rats has a positive effect on the emission of stress-induced 22-kHz calls, and the calls may be regulated by the activation of both androgen and estrogen receptors.

Design, Synthesis, and Biological Evaluation of Novel Investigational Nonapeptide KISS1R Agonists with Testosterone-Suppressive Activity

Metastin/kisspeptin is a 54 amino acid peptide ligand of the KISS1R receptor and is a critical regulator of GnRH secretion. The N-terminally truncated peptide, metastin(45-54), possesses a 10-fold higher receptor-binding affinity than full-length metastin and agonistic KISS1R activity but is rapidly inactivated in rodent plasma. We have developed a decapeptide analog [D-Tyr(45),D-Trp(47),azaGly(51),Arg(Me)(53)]metastin(45-54) with improved serum stability compared with metastin(45-54) but with decreased KISS1R agonistic activity. Amino acid replacements at positions 45-47 led to an enhancement of KISS1R agonistic activity and metabolic stability. N-terminal truncation resulted in a stable nonapeptide, [D-Tyr(46),D-Pya(4)(47),azaGly(51),Arg(Me)(53)]metastin(46-54), compound 26, which displayed KISS1R binding affinities comparable to metastin(45-54) and had improved serum stability. Compound 26 reduced plasma testosterone in male rats and is the first short-length metastin analog to possess testosterone suppressive activities. Compound 26 has led to the elucidation of investigational analogs TAK-683 and TAK-448, both of which have undergone clinical evaluation for hormone-dependent diseases such as prostate cancer.

Androgen action at the target musculature regulates brain‐derived neurotrophic factor protein in the spinal nucleus of the bulbocavernosus

We have previously demonstrated that brain-derived neurotrophic factor (BDNF) interacts with testosterone to regulate dendritic morphology of motoneurons in the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB). Additionally, in adult male rats testosterone regulates BDNF in SNB motoneurons and its target muscle, the bulbocavernosus (BC). Because BDNF is retrogradely transported from skeletal muscles to spinal motoneurons, we hypothesized that testosterone could regulate BDNF in SNB motoneurons by acting locally at the BC muscle. To test this hypothesis, we restricted androgen manipulation to the SNB target musculature. After castration, BDNF immunolabeling in SNB motoneurons was maintained at levels similar to those of gonadally intact males by delivering testosterone treatment directly to the BC muscle. When the same implant was placed interscapularly in castrated males it was ineffective in supporting BDNF immunolabeling in SNB motoneurons. Furthermore, BDNF immunolabeling in gonadally intact adult males given the androgen receptor blocker hydroxyflutamide delivered directly to the BC muscle was decreased compared with that of gonadally intact animals that had the same hydroxyflutamide implant placed interscapularly, or when compared with castrated animals that had testosterone implants at the muscle. These results demonstrate that the BC musculature is a critical site of action for the androgenic regulation of BDNF in SNB motoneurons and that it is both necessary and sufficient for this action. Furthermore, the local action of androgens at the BC muscle in regulating BDNF provides a possible mechanism underlying the interactive effects of testosterone and BDNF on motoneuron morphology. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 587-598, 2013.

Chronic khat (Catha edulis) and alcohol marginally alter complete blood counts, clinical chemistry, and testosterone in male rats

IntroductionKhat (Catha edulis) is a recreational psychoactive drug with psychostimulant properties. While the use of this drug is widespread in eastern Africa, including the Horn of Africa, surveys and anecdotal data show that its use has become cosmopolitan, with users now living in Europe and North America as well. Recent data in Uganda suggest an increasing pattern of simultaneous khat and ethanol use particularly among young adults. However, the effects of this pattern of use remain largely unknown, even though long-term use of either drug alone is known to be harmful. The aim of this study was to examine the toxic effects of simultaneous chronic administration of khat and ethanol on hematological parameters, clinical chemistry, and testosterone in a rat model.MethodsAdult male Sprague-Dawley rats were randomly assigned to one of six dose groups: 2 g/kg khat; 4 g/kg khat; 4 g/kg ethanol; combined khat and ethanol (4 g/kg each); control; and an untreated group. Treatments were given by gavage twice daily for 28 days, followed by determination of hematological parameters, blood clinical chemistry, and testosterone.ResultsEthanol alone significantly reduced platelet counts compared to control-, untreated and low-dose khat-treated rats; conversely low-dose khat significantly increased both the hemoglobin and hematocrit values, while ethanol alone also significantly increased the hemoglobin value compared to controls. Simultaneous khat and ethanol administration per se did not produce more toxic consequences in chronic use than either drug alone.ConclusionChronic short-term khat use and ethanol dependence individually produce noteworthy effects on the blood, but not on clinical chemistry or testosterone. Chronic short-term combined khat and ethanol use does not produce more toxic effects compared to use of either drug alone. This provides an opportunity for appropriate clinical interventions to avert the chronic long-term effects that result from use of these drugs of abuse.

Behavioral Effects of Physical Exercise and Exogenous Testosterone in Male Rats

The aim of our study was to analyze the interrelation between the effects of exogenous testosterone and physical exercise on behavior in adult male rats. During two weeks, male Wistar rats underwent a gradual daily-increasing forced swimming exercise (trained, groups, tr) or not (non-trained groups, ntr) and were injected with testosterone (TSt groups) or solvent olive oil, control, Ctrl groups). The average swimming times until reaching the platform in the Morris water maze were significantly shorter in the TSt tr group as compared to other groups during the first day. Intergroup differences between the results from other behavioral tests did not reach the significance levels. Our results indicate that the combination of testosterone administration and physical exercise leads to improvement of spatial working memory. Further studies are needed to uncover the mechanism of this effect.

Effects of 1800-MHz Radiofrequency Fields on Circadian Rhythm of Plasma Melatonin and Testosterone in Male Rats

Radiofrequency fields (RF) at 1800 MHz are known to affect melatonin (MEL) and testosterone in male rats, but it remains to be determined whether RF affected circadian rhythm of these plasma hormones. Male Sprague-Dawley rats were exposed to 1800-MHz RF at 208 μw/cm2 power density (SAR: 0.5762 W/kg) at different zeitgeber (ZT) periods of the day, including 0 (ZT0), 4 (ZT4), 8 (ZT8), 12 (ZT12), 16 (ZT16), and 20 (ZT20) h. RF exposure was 2 h/d for 32 d. From each rat, the concentrations of plasma MEL and testosterone were determined in plasma after RF exposure and compared with controls. The results confirmed the existence of circadian rhythms in the synthesis of MEL and testosterone, but revealed an inverse relationship in peak phase of these rhythms. These rhythms were disturbed after exposure to RF, with the effect being more pronounced on MEL than testosterone. The most pronounced effect of RF exposure on MEL and testosterone appears to be in rats exposed to RF at ZT 16 and ZT0 h, respectively. Data suggest that regulation of testosterone is controlled by MEL and that MEL is more sensitive to RF exposure.

Gender Differences in the Pharmacokinetics of Rivastigmine in Rats

The effect of gender on the pharmacokinetics of rivastigmine (CAS 123441-03-2) was studied in male and female Wistar rats following intravenous bolus administration. The area under the plasma concentration-time curve (AUC), apparent volume of distribution (Vd), systemic clearance (CL), and terminal plasma halflife (t1/2) of rivastigmine were compared between male and female rats. Compared to male rats, female rats exhibited higher plasma rivastigmine levels showing significantly (p < 0.05) larger AUC (226.77 vs. 149.68 ng h/ml), Vd (6.70 vs. 4.13 L), t1/2 (0.84 vs. 0.34 h) and a lower CL (5.51 vs. 8.35 L/h). The male rats had a 2.5 fold greater elimination rate constant than female rats (2.02 vs. 0.82 h(-1)). Gender had a significant effect on the pharmacokinetics of rivastigmine. Gender differences were reported due to gonadal hormones, and the observed difference in pharmacokinetics of rivastigmine might be attributed to testosterone in male rats.

Infradian Fluctuations in Serum Testosterone Levels in Male Laboratory Rats

The dynamics of serum testosterone was studied in laboratory male rats kept separately from females. Infradian rhythm of changes in testosterone level equal to 4 days and ultradian (within 24 h) periods equal to 160 and 480 min were detected. The maximum serum level of testosterone in male rats was synchronized with the greatest number of estrous females.

Anxiolytic-like Effect of Testosterone in Male Rats: GABAC Receptors Are Not Involved.

The effect of testosterone on anxiety-like behaviors has been the subject of some studies. There is evidence that testosterone modulates anxiety via GABA (gama aminobutyric acid) and GABAergic system. The involvement of GABAC receptors in those effects of testosterone on anxiety-like behaviors of the rats was investigated in the present study. A group of rats received subcutaneous injections of testosterone (5, 10 and 20 mg/kg). Two groups of rats received intracerebroventricular injections of either CACA (GABAC agonist, 0.125 μg/rat) or TPMPA (GABAC antagonist, 3 microg/rat) following administration of testosterone (5, 10 and 20 mg/kg). After the injections, the rats were submitted to the elevated plus-maze test of anxiety. The rats received testosterone alone, showed a decreased in anxiety-like behaviors (P< 0.01). Administration of either CACA or TPMPA did not modify animals' behavior compared to the rats received testosterone alone. The results of the present study showed that administration of testosterone induces anxiolytic-like behaviors in the rats and GABAC receptors possibly are not involved in the anxiolytic effect of testosterone.

Effect of Metronidazole on Spermatogenesis, Plasma Gonadotrophins and Testosterone in Male Rats

Metronidazole and it’s derivatives are drugs that have both antiprotozoal and anti bacterial effect.The reproductive toxicity of metronidazole has been shown in some studies. To investigate the effect of metronidazole on spermatogenesis in adult male rats, this study was designed. Eighteen wistar male rats (70-90days old) were randomly divided into three groups. Animals in group I (Control group) were administered the water. Animals in groups II, III were administered metronidazole at doses of 200 and 400 mg/kg/day for 60 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), luteiniging hormone (LH), testosterone assessment. In the 200 and 400 mg/kg groups, there were significant decreases in the testes and accessory sex organ weights, plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. It is concluded that metronidazole has a suppressive influence on spermatogenesis and sex hormones in rats.

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen receptor alpha (ERα) cell numbers in the hypothalamus, and their relationship to sexual performance in male rats. Young (3 months) and middle-aged (12 months) rats were given sexual behavior tests, then castrated and implanted with vehicle or testosterone capsules. Rats were tested again for sexual behavior. Numbers of AR and ERα immunoreactive cells were counted in the anteroventral periventricular nucleus and the medial preoptic nucleus, and serum hormones were measured. Middle-aged intact rats had significant impairments of all sexual behavior measures compared to young males. After castration and testosterone implantation, sexual behaviors in middle-aged males were largely comparable to those in the young males. In the hypothalamus, AR cell density was significantly (5-fold) higher, and ERα cell density significantly (6-fold) lower, in testosterone- than vehicle-treated males, with no age differences. Thus, restoration of serum testosterone to comparable levels in young and middle-aged rats resulted in similar preoptic AR and ERα cell density concomitant with a reinstatement of most behaviors. These data suggest that age-related differences in sexual behavior cannot be due to absolute levels of testosterone, and further, the middle-aged brain retains the capacity to respond to exogenous testosterone with changes in hypothalamic AR and ERα expression. Our finding that testosterone replacement in aging males has profound effects on hypothalamic receptors and behavior has potential medical implications for the treatment of age-related hypogonadism in men.

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

Several groups have recently shown that 17beta-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17beta-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17beta-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17beta-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5- or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax/Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17beta-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonad-intact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17beta-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17beta-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.