Testosterone In Male Rats Research Articles

Gonadal hormones modulate the potency of the disruptive effects of donepezil in male rats responding under a nonspatial operant learning and performance task

In contrast to estrogen in female rats, testosterone in male rats may decrease cholinergic activity in the brain, thereby attenuating behaviors mediated by the cholinergic system. To investigate this possibility, the interactive effects of the gonadal hormones and donepezil, an acetylcholinesterase (AChE) inhibitor, on the responding of male rats were examined under a multiple schedule of repeated acquisition and performance of response sequences and on AChE activity in specific brain regions. Donepezil dose-effect curves (0.56-10 mg/kg) were determined in males that were gonadally intact, gonadectomized (GX), GX with testosterone replacement (GX+T) or GX with estradiol replacement (GX+E). In all four groups, donepezil produced dose-dependent rate-decreasing and error-increasing effects in the acquisition and performance components. However, disruptions of response rate and accuracy in both components occurred at lower doses in GX and GX+E males than in intact males. The GX+E males also had the highest percentage of errors under control (saline) conditions in the acquisition components. In terms of AChE activity, GX males had higher levels in the prefrontal cortex, striatum and hippocampus, but lower levels in the midbrain, compared with intact males; hypothalamic and cortical levels were comparable for the GX and intact groups. Together, these results in male rats indicate that the potency of donepezil's disruptive effects on the responding under a complex operant procedure requiring learning and performance of response sequences depends upon the gonadal hormone status, and that the effects of testosterone on cholinergic activity vary among brain regions.

Donepezil differentially interacts with gonadal hormones in male rats responding under a multiple schedule of repeated acquisition and performance

Gonadal steroid hormones can mediate learning and memory, presumably by enhancing the functional status of cholinergic neurons. In contrast to the effects of estrogen in female rats, some evidence suggests that testosterone in male rats may decrease acetylcholine levels, and thus, the activity of the cholinergic system. The present study investigated the interactive effects of testosterone and donepezil, an acetylcholinesterase inhibitor, in subjects responding under a multiple schedule of repeated acquisition and performance of response chains. Donepezil dose‐effect curves (0.56‐10 mg/kg) were determined in males that were gonadally intact, gonadectomized, gonadectomized with testosterone replacement, or gonadectomized with estradiol replacement. For all four groups, donepezil produced dose‐dependent rate‐decreasing and error‐increasing effects in both the acquisition and performance components. Gonadally intact, GX, and GX+T males showed less disruption of response rate in both the acquisition and performance components than GX+E males. In terms of accuracy, GX+E males had the highest percentage of mean errors after control injections and also after donepezil administration in both the acquisition and performance components. Together, these data demonstrate that donepezil differentially interacts with gonadal hormones, and estrogen in particular, in male rats. Supported by DA 019625.

Free serum testosterone level in male rats treated with tribulus alatus extracts

The present study was undertaken to investigate the effect of Tribulus alatus extracts on free serum testosterone in male rats. Free serum testosterone level was measured in male rats treated with alcoholic extracts of the aerial part without fruits, fruits of Tribulus alatus and their fractions. All tested extracts showed significant increase in the level of free serum testosterone when compared to that of corresponding control, p < 0.05. Statistical comparison of all groups revealed that the maximum level was found in groups treated with chloroformic and ethanolic fractions of fruits extract. Tribulus alatus extract appears to possess aphrodisiac activity due to its androgen increasing property.

Effect of Inhalation Exposure to Gasoline on Sex Hormones Profile in Wistar Albino Rats

adult male and 12 female Wistar albino rats were used to measure the levels of the serum follicle stimulating hormone (FSH), the luteinizing hormone (LH), the estradiol (E2) and the progesterone in female rats, as well as the FSH, the LH and the testosterone in male rats, following 8-hour daily inhalation exposure to gasoline vapours for 6 weeks, to assess the effect of the vapours on the reproductive integrity of experimental animals. The results showed that the levels of serum FSH and LH obtained for female rats in the test group (3.48±0.03 and 19.97±1.20mIU/ml, respectively) were insignificantly lower (p>0.05), compared respectively to the levels obtained for female rats in the control group (3.62±0.12 and 20.06±0.23mlU/ml, respectively), whereas the levels of serum estradiol and progesterone obtained for female rats in the test group (25.02±2.32pg/ml and 0.18±0.02mg/ml, respectively) were significantly lower (p 0.05), compared to the levels obtained for male rats in the control group (2.75±0.14 and 2.93±0.12mIU/ml, respectively).At the same time, the level of serum testosterone in the male test rats (7.82±2.17ng/dl) was significantly higher (p<0.05), compared to the level in the male control rats 4.66±1.85ng/gl. The results of this study showed that the adverse effect of inhalation exposure to gasoline fumes on the reproductive integrity in rats is sex-dependent, with the females being more vulnerable.

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats

Fourteen days oral administration of therapeutic dose of Ampicillin (4mg/100g/day), Cloxacillin (6mg/100g/day) and Tetracycline (12mg/100g/day) separately to healthy adult male albino rats significantly reduced their serum testosterone level as assessed by enzyme immunoassay. The control group received equal volume of the vehicle (Normal saline) throughout the period of the treatment. A significant reduction (P Keywords : male infertility, antibiotics, tetracycline, ampicillin, serum testosterone, male reproductive organs, and antifertility Nigerian Journal of Health and Biomedical Sciences Vol. 5(1) 2006: 17-20

COCAINE‐INDUCED ALTERATIONS IN D2/D3 RECEPTOR FUNCTION IN MALE RATS WITH AND WITHOUT TESTOSTERONE REPLACEMENT

Previous studies in our laboratory indicate that testosterone modulates cocaine-induced locomotor activity in the male rat. In this study, functional autoradiography was used to investigate cocaine modulation of D2/D3 receptors in male rats. Adult Sprague-Dawley rats were orchidectomized and received an empty (GDX) or testosterone-filled (GDX-T) silastic implant. A week later, they received a daily injection of saline or cocaine (15 mg/kg,i.p.) for 5 days. On day 13 they received another cocaine injection (15 mg/kg, i.p.). To determine D2/D3 receptor function, quinpirole-stimulated [35S] GTPγ S binding was assessed in the striatum (STR) and nucleus accumbens (NAc). GDX males showed higher levels of D2/D3 signal transduction in the STR and NAc compared to GDX-T males. When rats were injected with cocaine, we observed that only GDX-T males showed an increase in quinpirole-stimulated [35S] GTPγ S binding in these brain areas. The cocaine paradigm for our studies did not induce behavioral sensitization in GDX-T males but it did in GDX males, which did not show robust changes in D2/D3 function in the brain areas studied. These data indicate that D2/D3 function is modulated by testosterone in male rats and suggest an inhibitory role of D2/D3 in behavioral sensitization. This work was supported partially by NIH grants U54 NS3905 04 (NINDS/SNRP); SO6-GM08224 (MBRS/SCORE), RR03051 (NCRR/RCMI); and R25 GM61838 (MBRS/RISE)

Effects of gonadal hormones on central nitric oxide producing systems

Nitric oxide-containing neurons are widely distributed within the CNS, including regions involved in the control of reproduction and sexual behavior. The expression of neuronal nitric oxide synthase is influenced by testosterone in male rat, and by estrogens in female. Moreover, nitric oxide synthase may co-localize with gonadal hormones’ receptors. Gonadal hormones may influence nitric oxide synthase expression in adulthood as well as during the development. In fact, in mice knockout for estrogen receptor alpha, the nitric oxide synthase-expressing population is deeply reduced in specific regions. In physiological conditions, the female in mammalian species is exposed to short-term changes of gonadal hormones levels (estrous cycle). Our recent studies, performed in the rat vomeronasal system and in mouse hypothalamic and limbic systems reveal that, in rodents, the expression of nitric oxide synthase-producing elements within regions relevant for the control of sexual behavior is under the control of gonadal hormones. The expression of nitric oxide synthase may vary according to the rapid variations of hormonal levels that take place during the estrous cycle. This seems in accordance with the hypothesis that gonadal hormone activation of nitric oxide–cyclic guanosine-monophosphate pathway is important for lordosis behavior, as well as that this system is activated during mating behavior. Finally, comparative data available for other vertebrates suggest that class-specific and species-specific differences occur in the nitric oxide synthase system of hypothalamus and limbic structures. Therefore, particular caution is needed to generalize data obtained from studies in rodents.

D24-hour changes in circulating prolactin, follicle-stimulating hormone, luteinizing hormone and testosterone in male rats subjected to social isolation.

BackgroundThis work analyzes the effect of social isolation (a mild stressor) on the 24-h variation of pituitary-testicular function in young Wistar rats, assessed by measuring circulating levels of prolactin, FSH, LH and testosterone.MethodsAnimals were either individually caged or kept in groups (4–5 animals per cage) under a 12:12 h light-dark cycle (lights on at 0800 h) for 30 days starting on day 35 of life. Rats were killed at 4-h intervals during a 24-h cycle, beginning at 0900 h.ResultsIsolation brought about a decrease in prolactin, LH and testosterone secretion and an increase of FSH secretion. In isolated rats the 24-h secretory pattern of prolactin and testosterone became modified, i.e., the maximum in prolactin seen in control animals at the beginning of the activity span was no longer detected, whereas the maximum in circulating testosterone taking place at 1700 h in controls was phase-delayed to 2100 h in isolated rats.ConclusionSocial isolation affects the 24-h variation of pituitary-testicular function in young rats. Secretion of prolactin, LH and testosterone decreases, and secretion of FSH increases, in isolated rats. The maximum in prolactin seen in group-caged rats at the beginning of the activity span is not observed in isolated rats. The maximum in circulating testosterone taking place at the second part of the rest span in controls is phase-delayed to the light-dark transition in isolated rats.

Adverse Effects of Environmental Toxicants, Octylphenol and Bisphenol A, on Male Reproductive Functions in Pubertal Rats

It has been proposed that a global decline in sperm counts, semen quality, and several male reproductive disorders are associated with exposure to environmental chemicals. Thus, the present study examined the effects of two estrogenic chemicals, octylphenol (OP) and bisphenol A (BPA), on epididymal sperm counts and sperm motility, luteinizing hormone (LH)-releasing hormone (LHRH)-stimulated plasma LH and steroid hormones, insulin-like growth factor I (IGF-I), and accessory reproductive organs in pubertal male Wistar rats. Fifty-day-old rats in the OP group (n=11) and BPA group (n=11) received daily sc injections of the respective chemical at a dose of 3 mg/kg bw dissolved in 0.2 mL DMSO. Rats in the control group (DMSO group; n=10) received 0.2 mL DMSO alone. After 2 wk of treatment, a jugular blood sample was taken, and, on the next day, a second blood sample was taken 1 h after an sc injection of LHRH (250 ng). After 5 wk of treatment, rats were deeply anesthetized and heart blood was collected. Epididymal sperm motility and sperm head counts were determined. LHRH increased plasma LH to higher levels in all groups, but the increases were significant (p<0.01) in the BPA and OP groups. However, despite higher LH levels after LHRH injection, the incremental responses of testosterone and pro-gesterone in the OP and BPA groups were small compared to those in the DMSO group, which showed a small LH response. After 5 wk of treatment, plasma testosterone levels were significantly (p<0.01) reduced in the OP and BPA groups and this was accompanied by reduced (p<0.05) epididymal sperm counts. However, the chemical-treated groups had high basal progesterone levels. No significant effects of chemicals on sperm motility parameters were noted. The chemical-induced increases (p<0.05) of the weight of ventral prostate gland were coincided with elevated plasma IGF-I levels in the BPA (p<0.05) and OP (p<0.01) groups. The present results demonstrated that OP and BPA can reduce sperm counts resulting from lowered plasma testosterone in male rats just after puberty. The enlarged ventral prostate gland may possibly be associated with increased plasma IGF-I, raising the possibility of a link between these chemicals and prostate diseases because IGF-I has been implicated in the pathogenesis of human prostate cancers.

Two organizational effects of pubertal testosterone in male rats: transient social memory and a shift away from long-term potentiation following a tetanus in hippocampal CA1

The organizational role of pubertal androgen receptor (AR) activation in synaptic plasticity in hippocampal CA1 and in social memory was assessed. Earlier data suggest pubertal testosterone reduces adult hippocampal synaptic plasticity. Four groups were created following gonadectomy at the onset of puberty: rats given testosterone; rats given testosterone but with the AR antagonist flutamide, present during puberty; rats given testosterone at the end of puberty; and rats given cholesterol at the end of puberty. A tetanus normally inducing long-term potentiation (LTP) was used to stimulate CA1 in the urethane-anesthetized adults during the dark phase of their cycle. Social memory was assessed prior to electrophysiology. Social memory for a juvenile rat at 120 min was seen only in rats not exposed to AR activation during puberty. Pubertal AR activation may induce the reduced social memory of male rats. Early CA1 LTP occurred following tetanus in rats with no pubertal testosterone. Short-term potentiation occurred in rats exposed to pubertal testosterone. Unexpectedly, rats with pubertal AR activation developed long-term depression (LTD). The same pattern was seen in normal male rats. Lack of LTP during the dark phase is consistent with other data on circadian modulation of CA1 LTP. No correlations were seen among social memory scores and CA1 plasticity measures. These data argue for two organizational effects of pubertal testosterone: (1) CA1 synaptic plasticity shifts away from potentiation toward depression; (2) social memory is reduced. Enduring effects of pubertal androgen on limbic circuits may contribute to reorganized behaviors in the postpubertal period.

Gonadal steroids differentially regulate the messenger ribonucleic acid expression of pituitary orexin type 1 receptors and adrenal orexin type 2 receptors.

Hypothalamic prepro-orexin as well as pituitary and adrenal orexin receptors are gender-specifically expressed. To assess the regulation by gonadal steroids, we investigated the effect of 17beta-estradiol in female and of testosterone in male rats on prepro-orexin and orexin receptor mRNA expression. Rats were either sham-operated or gonadectomized and subsequently treated with placebo, 17beta-estradiol, or testosterone for 21 d. Tissue mRNA levels of prepro-orexin, orexin type-1 (OX(1)), and orexin type-2 (OX(2)) receptors were measured using quantitative real-time RT-PCR. In female rats, pituitary OX(1) receptor mRNA levels were increased 12-fold after ovariectomy compared with sham- operated rats. The increase of pituitary OX(1) receptor mRNA was inhibited by treatment with 17beta-estradiol. Adrenal mRNA levels of OX(2) receptors in ovariectomized rats were increased 2-fold compared with sham-operated rats and were also reduced by treatment with 17beta-estradiol. In male rats, orchidectomy increased the mRNA levels of pituitary OX(1) receptors compared with sham-operated rats. In contrast, adrenal OX(2) receptor mRNA was reduced after orchidectomy. Testosterone treatment reversed the effect of orchidectomy on pituitary OX(1) and adrenal OX(2) receptors. In the hypothalamus, no differences were found in the mRNA levels of prepro-orexin, OX(1), and OX(2) receptors between sham-operated, placebo-treated, and steroid-treated female or male rats. Our results indicate that gonadal steroids differentially regulate pituitary OX(1) receptors and adrenal OX(2) receptors in male and female rats and may contribute to specific sex- dependent neuroendocrine and endocrine actions of orexins.

Inhibition of aldosterone production by testosterone in male rats.

In vivo and in vitro experiments were designed to assess the effect of testosterone on aldosterone secretion in male rats. Orchidectomized rats were injected subcutaneously with oil or testosterone propionate ([TP] 2 mg/kg) for 7 days. Intact rats were injected with oil only. The results indicate that the plasma aldosterone level was higher in orchidectomized versus intact and TP-replaced rats. In the in vitro study, testosterone caused a marked decrease of aldosterone secretion by zona glomerulosa (ZG) cells, but failed to alter the accumulation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Testosterone significantly decreased the corticotropin (ACTH)-stimulated production of aldosterone and accumulation of cAMP in rat ZG cells. The conversion of corticosterone to aldosterone and of 25-OH-cholesterol to pregnenolone, as well as angiotensin II (ANG II)-stimulated production of aldosterone, were decreased by testosterone. These results suggest that testosterone inhibits the basal and ANG II- and ACTH-stimulated release of aldosterone, via inhibition of aldosterone synthase activity and cytochrome P-450 side-chain cleavage (P450scc) activity, and ACTH-stimulated cAMP accumulation in rat ZG cells.

Affective properties of intra-medial preoptic area injections of testosterone in male rats

On alternating days, adult male Long–Evans rats implanted with unilateral cannulae in the medial preoptic area (MPOA) received intracerebral injections of testosterone (0.05, 0.1 or 0.2 μg/0.5 μl), or saline immediately prior to confinement for 30 min to one of two compartments of a place preference apparatus. All rats received 8 days of pairings (4 hormone and 4 saline). On day 9, the rats were given a hormone-free 20-min test session during which they had access to all compartments of the apparatus. Intra-MPOA injections of testosterone (0.1 μg) produced a conditioned place preference, while injections of a higher dose (0.2 μg) produced a conditioned place aversion. The rewarding effects of intra-MPOA testosterone may in part mediate the facilatory effects of testosterone on motivational aspects of sexual behavior.

Neonatal Castration and Adult Responsiveness to Testosterone in Male Rats: An Interstrain Comparison

WALL, A. AND B. J. MEYERSON. Neonatal castration and adult responsiveness to testosterone in male rats: An interstrain comparison. PHYSIOL BEHAV 62(6) 1371–1378, 1997.—We have previously demonstrated that the spontaneously hypertensive rat (SHR) has a lower central nervous responsiveness to testosterone than its normotensive counterpart the Wistar–Kyoto rat (WKY). The adult psychoendocrine response capacity depends on a neonatal testosterone surge. On that basis, we compared the effects of neonatal endocrine manipulation on the adult responsiveness to testosterone in the SHR, WKY, and yet another breed of Wistar (Wi) male rats. Interstrain differences in testosterone-induced copulatory behavior at three different doses of testosterone propionate (TP) were investigated. Neonatal treatments were as follows: TP (0.25 mg/animal) given on postnatal days (PND) 0, 2, and 4 (SHR and Wi only) or castration PND 0, 10, or 50. Neonatal TP treatment impaired copulatory performance in the adult SHR but not in the Wi. Neonatal castration improved the responsiveness to TP in the SHR but less so in WKY, whereas no evident effects were seen in the Wi. No significant interstrain differences in plasma testosterone were observed 2, 6–12, or 24 h postpartum. The demonstrated interstrain differences suggest not only that the adult responsiveness to testosterone is established on the basis of the neonatal gonadal secretion as such but that this secretion is kept to an optimal level with respect to subsequent hormone-sensitive mechanisms.

The Effect of Esterification on the Release of Testosterone and Estradiol from Silicone Implants

Four experiments were conducted to determine the effect of esterification on the release of testosterone and estradiol from capsule-type silicone implants. In castrated male rats testosterone propionate and testosterone enanthate implants increased (P < .05) blood testosterone concentrations and seminal vesicle weights more than empty and testosterone implants. Testosterone propionate and testosterone enanthate implants released 4 times and 10 times, respectively, more equivalent testosterone per cm2 per day than testosterone implants. The increase in blood testosterone concentrations was proportional to the increase in implant release rate for testosterone propionate, but not for testosterone enanthate. Although estradiol- 17β implants increased (P < .05) uterine weights of ovariectomized rats, uterine weights in estradiol benzoate implanted ovariectomized rats were 1.3 times greater than in estradiol-17β implanted rats. Estradiol benzoate implants released less than 0.5 times the amount of equivalent estradiol per cm2 per day than estradiol- 17β implants.

Cervical sympathectomy affects gonadotropin-releasing hormone, luteinizing hormone and testosterone in male rats.

To examine the effects of bilateral cervical sympathectomy on the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and testosterone (TS), 24 male rats were divided into four groups: control (C), light (L), sympathectomy (S), and light-sympathectomy (LS) groups. The C and S groups were kept under a 12-h light-dark cycle and the L and LS groups were kept under continuous light for 2 weeks. After 2 weeks, blood was collected and the rats were perfused with a fixative. GnRH neurons in the hypothalamus were stained immunohistochemically, and serum LH and TS levels were measured by radioimmunoassay. Although the difference in the number of GnRH neurons between the C and S groups was not significant, the L group was significantly lower than the C or LS groups. The serum LH and TS levels in the L group were higher than in the other groups. The present results suggest that continuous light increases GnRH secretion in the hypothalamus, followed by increased secretions of LH in the pituitary and TS in the testes, and bilateral cervical sympathectomy under continuous light inhibits these hormonal changes. However, a normal circadian rhythm does not affect gonadotropin secretion. Therefore, long-term and repeated stellate ganglion block may inhibit the increases of GnRH, LH, and TS secretions induced by continuous light.

Cervical sympathectomy affects gonadotropin-releasing hormone, luteinizing hormone and testosterone in male rats

Cervical sympathectomy affects gonadotropin-releasing hormone, luteinizing hormone and testosterone in male rats

Temporal changes in the serum levels of gonadotrophins and testosterone in male rats bearing subcutaneous implants of 5 alpha-dihydrotestosterone.

This study has assessed the effect of s.c. implants of 5 alpha-dihydrotestosterone (DHT) on the blood levels of testosterone and gonadotrophins in intact and castrated adult male rats. The rats were bled via cardiac puncture at 1, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days after DHT implantation. On days 28 and 49 post-implantation, rats were injected with LHRH (25 ng) and bled 15 min later. In intact rats bearing DHT implants, the serum levels of LH and testosterone were suppressed significantly with no significant changes in FSH levels. Ventral prostate, seminal vesicles and the pituitary were reduced significantly in weight when compared with controls with empty implants. DHT significantly inhibited LHRH-induced release of FSH in intact rats. In castrated rats, DHT implants inhibited the secretion of both LH and FSH, with a rise in serum DHT levels. DHT stimulated the LHRH-induced release of LH but inhibited FSH. DHT implants increased the weight of the seminal vesicles and ventral prostate but inhibited the weight of the pituitary when compared to castrated rats bearing empty implants. This study demonstrates specific inhibition of serum LH and testosterone by DHT implants in intact adult rats.

Age-associated changes and sex differences in urinary 6-sulphatoxymelatonin circadian rhythm in the rat

The circadian rhythm of 6-sulphatoxymelatonin (aMT6s) excretion has been determined in male and female rats at 3 weeks and at 2, 8, 14 and 20 months of age. All animals have a pronounced circadian pattern of aMT6s excretion under a 12 hour dark: 12 hour light cycle. A significant increase in aMT6s excretion is observed from 3 weeks to 14 months followed by a decrease at 20 months. There is a highly significant correlation between aMT6s excretion and body weight (r = 0.73 for female rats and r = 0.74 for male rats; p values are all less than 0.001). Thus, a decrease in aMT6s excretion associated with increasing age occurs when body weight is taken into consideration. aMT6s excretion is higher in males at 3 weeks and at 2 and 8 months of ages. Urinary testosterone in male rats and estradiol in female rats increase from 3 weeks to 8 months and decrease at older ages. These data suggest that increase of body weight from 3 weeks to 14 months is an important factor responsible for the age-related alteration. The sex differences in aMT6s excretion in younger rats may be associated with their sex hormonal milieu.

Differential effects of cimetidine, ranitidine and famotidine on the hepatic metabolism of estrogen and testosterone in male rats

The effect of alcohol (1.2 and 2.0 g/kg) on the urinary testosterone-to-epitestosterone (T/E) ratio was studied by two experiments each conducted with four healthy females and males. The intake of 2.0 g/kg of ethanol within 5 h in the evening significantly increased plasma testosterone concentration and ratio of T/E in urine collected next morning in females. The results suggest that alcohol increases the T/E ratio more in females than in males. The effect of high doses of alcohol on urinary T/E ratio must be kept in mind when doping tests are performed during training periods.