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.     

Effects of testosterone on spatial learning and memory in adult male rats

A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting 7 days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects.     

Adrenocorticotropin secretion rates following histamine injection in adult and newborn dogs.

The metabolic clearance rate (MCR) for ACTH in adult dogs was previously shown not to vary significantly with varying plasma ACTH concentrations or among dogs. This is confirmed here for pups aged 1-7 days. Hence, ACTH secretion rates can be continuously calculated from a continuous function of plasma ACTH vs. time. Each of seven adult dogs under Nembutal anesthesia received two or three intravenous (i.v.) injections of histamine with increasing doses. The first injections in each dog ranged from 7 to 50 mug/kg, while the last dose was 62-108 mug/kg. A total of 16 injections were given. Twelve pups (two litters of six) aged 1-7 days each received one injection of histamine of 76-116 mug/kg (i.v.). ACTH concentrations in plasma were determined by an adrenal cell suspension bioassay before, and 6 times after each injection. Nine pups also underwent determinations of their MCR for ACTH, with plateau concentrations determined at three times during an ACTH infusion. Continuous curves of ACTH secretion rates were calculated for all 28 histamine injections, showing that all except the 1-day-old pups secrete considerable ACTH when stressed. Compared to adult dogs, the pups show lower secretion rate peaks and shorter periods of rapid secretion. Changes in plasma glucocorticoids also suggest that the adrenal cortex of newborn dogs can respond to ACTH by increased glucocorticoid secretion.     

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.     

睾丸去神经对大鼠半去势诱导的睾酮代偿性分泌的影响

在成年大鼠,半去势可以在促性腺激素没有明显改变的情况下导致睾丸静脉血液中睾酮浓度代偿性增加,其机理尚不明了。本研究以成年大鼠为实验动物,检验睾酮的代偿性增加是否受到睾丸去神经的影响。睾丸去神经（ｉｎｆｅｒｉｏｒ ｓｐｅｍａｔｉｃ ｎｅｒｖｅｓ,ＩＳＮ或ＩＳＮ ｐｌｕｓ ｓｕｐｅｒｉｏｒ ｓｐｅｒｍａｔｉｃ ｎｅｒｖｅｓ,ＩＳＮ－ＳＳＮ）手术２周后开始半去势实验,半去势之前和半去势之后６和２４ｈ,     

Seasonal pattern of LH and testosterone secretion in adult male fallow deer, Dama dama

At monthly intervals during the year blood samples were collected every 20 min for 12 h from 4 entire and 2 prepubertally castrated adult fallow deer bucks. In the entire bucks there were seasonal changes in mean concentrations and pulse frequencies of plasma LH. Mean concentrations in late summer and autumn were 3-6 times higher than during other seasons. LH pulse frequency was low (0-1 pulses/12 h) during most of the year and increased only during the 2-month period (January and February) that marked the transition from the non-breeding season to the autumn rut. During this period there was a close temporal relationship between pulses of LH and testosterone. However, during the rutting period (March and April) episodic secretion of testosterone, manifest as surges in plasma concentrations of 4-6 h duration, was not associated with any detectable pulses in LH although mean plasma concentrations of LH remained elevated. During the rut, the surges of plasma testosterone occurred at similar times of the day. Plasma profiles in May indicated very low concentrations of LH and testosterone secretion in the immediate post-rut period. Castrated bucks exhibited highly seasonal patterns of LH secretion, with mean plasma LH concentrations and LH pulse frequency being lowest in November (early summer) and highest in February and March (late summer-early autumn). Mean concentrations and pulse frequency of LH in castrated bucks were higher than for entire bucks at all times of the year.     

Stress-induced suppression of testosterone secretion in male alligators

In order to test the effect of acute stress on gonadal hormone secretion in reptiles, six mature male alligators were captured, and a blood sample was taken within 5 min of capture. Additional blood samples were taken at timed intervals for up to 41 hr, and plasma testosterone and corticosterone were measured by radioimmunoassay. Plasma testosterone declined to 50% of the initial value by 4 hr and dropped to less than 10% of initial by 24 hr. Plasma corticosterone increased during the first 12 hr, declined at 24 hr, and rose again at 40 hr. Blood samples from male alligators collected in North and South Carolina, south Florida, and in south Louisiana in two consecutive breeding seasons were also assayed for testosterone and corticosterone. In these populations there were significant differences in mean plasma testosterone and corticosterone levels. Elevated corticosterone levels were consistently seen in alligators caught in traps and from which a blood sample was taken several hours later. Plasma testosterone, although consistently lower in trapped alligators, did not show a negative correlation with plasma corticosterone. Farm-reared alligators bled once, released, and bled again at 24 hr also showed a highly significant suppression of testosterone secretion. These results demonstrate that stress has a rapid and dramatic effect on testicular steroid secretion in both farm-reared and wild alligators.     

Compensatory testosterone secretion in unilaterally orchidectomized rats

Blood and testis samples were taken from rats 3 weeks after unilateral (sinistral) orchidectomy or sham operation to study the regulation of circulating testosterone. Although plasma testosterone concentrations did not differ, the concentration of testicular testosterone was twofold greater in orchidectomized rats than in sham operated controls. At autopsy, weights of right testes as well as Leydig cell number of orchidectomized and control rats were similar. These observations indicate that, after unilateral orchidectomy, compensatory hypersecretion is not related to compensatory testicular hypertrophy.     

Moderate increases in peripheral blood estradiol concentration in the adult ram do not directly inhibit testosterone secretion.

Two experiments were conducted in July with adult Dorset x Leicester x Suffolk rams to determine whether increases of 150 or 300% in estradiol (E2) concentration in peripheral blood (from 6.3 +/- 0.8 pg/mL in control rams) would affect testosterone secretion directly as well as indirectly via the hypothalamic-pituitary axis. After 4 days of estradiol treatment (experiment 1) provided with subcutaneous polydimethylsiloxane implants filled with crystalline estradiol, luteinizing hormone (LH) and testosterone secretions were reduced by 50% (p < 0.05) in both groups of rams because of subtle decreases in pulse frequencies and amplitudes. Estradiol treatments were also associated with decreases in mean follicle-stimulating hormone (FSH) concentration (30-50% in both groups, p < 0.05) and increases in mean prolactin concentration (35% in low-E2 group; 105% in high-E2 group, p < 0.05), but testicular responsiveness to an LH challenge (single intravenous dose, 10 micrograms NIH-LH-S25) remained normal. When along with estradiol treatment, 10-micrograms doses LH were given every 80 min (experiment 2), testosterone secretion increased by 265% (p < 0.05) in both treated and control rams. Relative to day -1, secretion on day 4 was characterized by higher (p < 0.05) pulse frequencies and baseline concentrations and lower (p < 0.05) pulse amplitudes; values for all characteristics were similar to those for Dorset x Leicester x Suffolk rams in the breeding season. Interestingly, the decreases in mean FSH concentration brought about by estradiol and (or) LH treatments were not any greater than in experiment 1, and estradiol's ability to elevate mean prolactin concentration was blocked completely.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenocorticotropin acutely increases adrenal polyphosphoinositides.

After adrenocorticotropin (ACTH) treatment for 15 min, adrenal levels of diphosphoinositide and triphosphoinositide appear to increase severalfold. Several other adrenal phospholipids are not appreciably affected by such treatment. Rapid changes in polyphosphoinositides may play a role in hormonal modulation of membrane-associated metabolic events.     

The effect of agouti-related protein on growth hormone secretion in adult male rats

Agouti-related protein (AGRP) and neuropeptide Y (NPY) are synthesized in the same neurons in the hypothalamic arcuate nucleus. We have previously shown that NPY/AGRP neurons contain growth hormone (GH) receptor mRNA, and are activated following systemic GH administration. We also reported that NPY inhibits GH secretion when administered centrally. In this study, we have examined the effect of AGRP on GH secretion. Central administration of AGRP (83-132) as a single injection of 1 or 10 microg/rat, or chronic treatment of 1 microg/rat, every 12 h for 7 days, did not alter the GH secretory pattern of adult male rats. AGRP (83-132) at doses of 1-100 nM (4 h) did not alter baseline- and GHRH-induced GH secretion from the rat pituitary cell cultures. These results suggest that AGRP does not play a significant role in the feedback regulation of the GH secretion.     

Short-term fasting leads to inhibition of responsiveness to LH-stimulated testosterone secretion in the adult male bonnet monkey

A variety of stressors including fasting profoundly inhibit reproductive function in mammals. Although the effect of short-term fasting on gonadotropic axis is well established, the direct effects of fasting on gonads have not been reported. The objectives of the present experiments were to examine the effect of short-term fasting on circulating luteinizing hormone (LH) and testosterone (T) secretion, and to determine the responsiveness of testis to exogenous recombinant human (rh) LH treatment in male bonnet monkeys. In addition, an experiment was carried out to examine whether brief inhibition of endogenous LH secretion causes alteration in testicular responsiveness. Adult male monkeys were fasted for 1 day for examining the circulating endocrine hormone concentrations and challenged with rhLH injection 1 day after fasting. Food withdrawal for 1 day resulted in significant (P<0.05) decrease in LH, T and increase in cortisol concentrations. Surprisingly, T secretion in response to direct stimulation of Leydig cells by LH was not observed in fasted monkeys. In fed monkeys, treatment with Antide (a specific gonadotropin releasing hormone receptor antagonist to inhibit pituitary LH secretion) for 1 day did not compromise T secretion stimulated by rhLH, suggesting that loss of responsiveness of testis to exogenous LH treatment in fasted monkeys was not because of interruption in pituitary LH stimulation of the testis. The results indicate that short-term fasting in adult male monkeys cause inhibition of LH and T secretion, and inhibition of responsiveness of testis to LH stimulation.     

Elevated spring testosterone increases parasite intensity in male red grouse

The expression of testosterone-dependent sexual traits mightsignal the ability of their bearers to cope with parasite infections.According to the immunocompetence handicap hypothesis (IHH),such signals would be honest because physiological costs oftestosterone, such as a reduced ability to control parasiteinfections, would prevent cheating. We tested whether testosteronewould affect the outcome of a standardized parasite challengein red grouse, using a main parasite of the species, the nematodeTrichostrongylus tenuis. We caught males in spring, removedtheir nematode parasites, and implanted them with testosteroneor empty implants, as controls. After 1 month, they were reinfectedwith a standard dose of infective T. tenuis parasites. Whenchallenged, testosterone males had relatively less globulinrelative to albumin plasma proteins than control males, an indicationthat they had experienced increased physiological stress. Testosterone-treatedmales had significantly more T. tenuis parasites than controlsin the next autumn and also had more coccidia and lost moreweight than controls. Testosterone-treated males neverthelessbenefited from their elevated spring testosterone: they hadbigger sexual ornaments than controls both in spring and autumn,and they tended to have a higher pairing and breeding successthan controls. Our results supported the IHH in showing thatelevated testosterone impaired the ability of males to copewith a standardized challenge by a dominant parasite. Testosteronethus plays a key role in mediating trade-offs between reproductiveactivities and parasite defense, and testosterone-dependentcomb size might honestly signal the ability of red grouse tocontrol T. tenuis infection.     

Effects of castration on androstenedione, testosterone and dihydrotestosterone plasma levels in adult male rats

In the present study we investigated the effects of castration on androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) plasma levels in adult male rats 5 and 47 days after castration. In another group of 60-day-old castrated rats, the three steroids have been evaluated during testosterone propionate administration. Our data show that 5 days after orchiectomy all three steroids were significantly decreased (p less than 0.001) with respect to control values. 47 days after orchiectomy, T and DHT were also significantly decreased with respect to the control group. In both groups of orchiectomized rats the A/T ratio increased significantly with respect to controls. On the contrary, the T/DHT ratio sharply decreased. This suggests that DHT, in orchiectomized rats, could derive from precursors other than T. A negative correlation between A and the T/DHT ratio was observed 47 days after castration in adult animals and emphasized upon testosterone propionate administration. In the latter group, T was significantly lower while A is significantly augmented with respect to control values. Finally, the above-mentioned negative correlation indicates a possible prevalent role of A in contributing to the circulating levels of DHT in adult orchiectomized rats.     

Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats

The kisspeptins are KiSS-1 gene-derived peptides that signal through the G protein-coupled receptor-54 (GPR54) and have recently been shown to be critical regulators of reproduction. Acute intracerebroventricular or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis. This effect is thought to be mediated via the hypothalamic gonadotropin-releasing hormone (GnRH) system. Chronic administration of GnRH agonists paradoxically suppresses the HPG axis after an initial agonistic stimulation. We investigated the effects of continuous peripheral kisspeptin administration in male rats by use of Alzet minipumps. Initially we compared the effects of acute subcutaneous administration of kisspeptin-10, -14, and -54 on the HPG axis. Kisspeptin-54 produced the greatest increase in plasma LH and total testosterone at 60 min postinjection and was used in the subsequent continuous administration experiments. Chronic subcutaneous long-term administration of 50 nmol kisspeptin-54/day for 13 days decreased testicular weight. Histological examination showed degeneration of the seminiferous tubules associated with a significant decrease in the circulating levels of the testes-derived hormone, inhibin B. Plasma free and total testosterone were also lower, although these changes did not reach statistical significance. Further studies examined the effects of shorter periods of continuous kisspeptin administration. Subcutaneous administration of 50 nmol kisspeptin-54 for 1 day increased plasma LH and testosterone. This effect was lost after 2 days of administration, suggesting a downregulation of the HPG axis response to kisspeptin following continuous administration. These findings indicate that kisspeptin may provide a novel tool for the manipulation of the HPG axis and spermatogenesis.     

Effect of mammalian gonadotropins on testosterone secretion in male alligators

Male farm-reared alligators were injected with mammalian FSH, LH, hCG, prolactin, or saline. A blood sample was taken immediately prior to injection of hormone and at 24 h postinjection. Testosterone concentrations in the plasma were then determined by radioimmunoassay. Only the alligators injected with FSH showed a significant increase in plasma testosterone. In a second series of experiments male alligators were injected with ovine LH, ovine FSH, or saline and bled at 0, 2, 4, 16, and 24 h postinjection. Again, only the alligators injected with FSH showed significant increases in plasma testosterone at 16 and 24 h postinjection. Mammalian LH does not appear to stimulate testosterone secretion in male alligators.     

Effects of increased testosterone secretion on the behavior of adult male rhesus living in a social group.

Selected members of an all-male social group of rhesus monkeys were treated with twice-weekly injections of human chorionic gonadotropin (HCG) to determine the effects of the consequently increased androgen secretion on social behavior. Radioimmunoassay of blood samples confirmed significant increases in serum testosterone levels in each of 4 subject, but only 3 of these showed significant behavioral changes. The basic social structure of the group, including the dominance hierarchy, was not disrupted by the treatment with HCG. Rather, the behavioral changes which did not occur appeared to be intensifications of previously existing social relationship.