Protection of adrenal and male gonadal functions by androgen in lead-treated rats.

The potential health hazard of the large amounts of Lead that occurs in canned baby food, domestic water from lead-lined tanks and, in printing and petroleum industries. Lead acetate administration at a does of 8 mg/kg body weight for 21 days resulted a significant increase in adrenal steroidogenic enzyme (Delta5-3beta- HSD) and serum levels of corticosterone, while serum levels of testosterone, FSH, LH and testicular spermatogenesis were decreased in albino rats. But lead-treated rats received exogenous testosterone for the last 14 days of lead treatment, showed prevention of adrenocortical hyperactivity by decreasing adrenal Delta5-3beta-HSD activity and serum level of corticosterone. Testosterone administration also increased serum level of testosterone, FSH and LH along with spermatogenesis. The results suggest that testosterone supplementation in lead-treated rats protects adrenocortical activity and testicular spermatogenesis.

Estrogenic inhibition of the hepatic synthesis of alpha2u globulin in the rat.

The hepatic synthesis of the androgen-dependent urinary protein in the rat, called alpha2u globulin, is strongly inhibited by estrogens. In mature male rats, treatment with estradiol-17beta (0.5 mug/g body weight) completely inhibits alpha2u synthesis within 6-7 days. Following withdrawal of estrogen treatment alpha 2u synthesis is not reinitiated for approximately 20 days. Parabiotic joining of estrogen-suppressed male rats with their normal littermates within this lag period fails to change the preparabiotic pattern of alpha2u synthesis in the respective partners. Besides estradiol-17beta, other estrane derivatives such as estrone, estriol and estradiol-17alpha were also found to inhibit the synthesis of alpha2u globulin. All of the above estrane derivatives which inhibit alpha2u synthesis are also found to inhibit the uptake of 5alpha-dihydrotestosterone by the hepatic cytosol androgen binding protein of the mature male rat. Unlike cycloheximide, a known translational inhibitor, estradiol-17beta does not inhibit alpha 2u synthesis in the perfused rat liver.

Effect of intraventricular injection of 5,6-dihydroxytryptamine on spermatogenesis and plasma testosterone levels in the rat.

Quantitative evaluation of spermatogenesis at stage VII of the cycle of the seminiferous epithelium and radioimmunoassay of plasma testosterone were performed in adult Wistar rats after intraventricular injection of 5,6-dihydroxytryptamine (5,6-DHT). The rats were killed 2, 10 and 21 days after injection. Brain 5-hydroxytryptamine (5-HT) and plasma testosterone levels were found to be significantly lower in all rats treated with 5,6-DHT. A significant reduction in step 7 spermatid count was also observed after 10 and 21 days. Supplementation with human chorionic gonadotrophin for 21 days in rats injected with 5,6-DHT partially prevented the step 7 spermatid degeneration and increased testosterone levels without producing any effect on brain concentrations of 5-HT. These results suggest that changes in testicular steroidogenesis and spermatogenesis are secondary to pituitary gonadotrophin release which, in turn, is under the influence of brain 5-HT neurones.

Effect of dihydrotestosterone on serum concentrations of alpha 2u-globulin and on spermatogenesis in melatonin-treated rats.

Adult male rats were given s.c. injections of melatonin (400 micrograms/100 g body weight per day) for 14 days. On day 15, the weights of the testis and accessory sex organs were less, testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was inhibited, spermatogenesis was suppressed and serum levels of gonadotrophins, testosterone and alpha 2u-globulin were decreased compared with control animals injected with vehicle. In a third group of rats given the same dose of melatonin for 14 days, administration of dihydrotestosterone (DHT) at a dose of 25 micrograms/100 g body weight per day on days 8-14 resulted in serum levels of alpha 2u-globulin, FSH, LH and testosterone and testicular 17 beta-HSD activity similar to those seen in vehicle-injected control animals. Weights of the testes and accessory sex organs and spermatogenesis were normal after administration of DHT in melatonin-treated rats. In another group of rats, the depressive effects of melatonin treatment on plasma gonadotrophins were reversed by the administration of alpha 2u-globulin on days 8-14. It was concluded that treatment with DHT prevents the depressive action of melatonin on testicular function by inducing the synthesis of alpha 2u-globulin.

Pimozide-induced chronic hyperprolactinaemia and quantitative initiation of spermatogenesis in maturing rats.

When pimozide was given to maturing rats, a rise in the level of prolactin in the serum was accompanied by a fall in LH. There was also incomplete initiation of spermatogenesis as well as simultaneous adrenal hypertrophy. Bilateral adrenalectomy failed to prevent hyperprolactinaemia-induced antispermatogenic response, while a significant ameliorating effect was observed with LH, indicating that hyperprolactinaemia influenced the quantitative initiation of spermatogenesis by affecting the secretion of LH.

Effect of thyroidectomy, and thyroxine and alpha 2u-globulin replacement therapy on testicular steroidogenic and gametogenic activities in rats.

Adult male rats were thyroidectomized and killed after 22 days of treatment. Thyroidectomy lowered the weights of testes and accessory sex organs, decreased the activities of testicular delta 5-3 beta- and 17 beta-hydroxysteroid dehydrogenases (HSD), and diminished spermatogenesis, serum levels of testosterone and alpha 2u-globulin. Supplementation with thyroxine at a dose of 5 micrograms/100 g body weight per day for 21 days or supplementation with alpha 2u-globulin at a dose of 1.5 mg/rat per day for 21 days in thyroidectomized animals partially reversed the decrease in HSD activities and serum concentrations of testosterone and alpha 2u-globulin, while spermatogenesis was restored to normal. The weights of testes and accessory sex organs were also reinstated after supplementation with thyroxine or alpha 2u-globulin in thyroidectomized rats in comparison with thyroidectomized animals. It was concluded that alpha 2u-globulin may be an intermediary in the thyroid hormone control of testicular function.

Effect of corticosterone on serum concentrations of alpha 2 micro-globulin and on spermatogenesis in oestrogen-treated rats.

Treatment of adult male rats with oestradiol-17 beta (50 microgram/100 g body wt per day for 7 days) resulted 14 days later in reduced levels of alpha 2 micro-globulin in serum and inhibition of spermatogenesis. Administration of corticosterone (2 mg/day) for 14 days to oestrogen-treated rats raised the concentration of alpha 2 micro-globulin in the serum and prevented spermatogenic degeneration. It is concluded that endogenous alpha 2 micro-globulin induced by corticosterone may play a role in spermatogenesis in oestrogenized rats.

Effect of alpha 2u-globulin on serum concentration of gonadotrophins and testicular activity in oestrogen-treated rats.

Adult male rats were given injections of oestradiol-17 beta (50 micrograms/100 g body wt per day) for 7 days. When they were killed 14 days after the last injection, serum levels of gonadotrophins and testosterone and weights of accessory sex organs were less, testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was suppressed and spermatogenesis was inhibited. Administration of alpha 2u-globulin (1.5 mg/day) for 14 days to oestrogen-treated rats and for 10 days to control rats resulted in increased concentrations of gonadotrophins and testosterone in the serum. Accessory sex organ weight and spermatogenesis appeared to be normal while 17 beta-HSD activity increased in oestrogen-treated rats after treatment with alpha 2u-globulin. It was concluded that alpha 2u-globulin has an effect on testicular function in oestrogenized rats by inducing gonadotrophin and testosterone synthesis.

Effect of lithium chloride on spermatogenesis and testicular steroidogenesis in mature albino rats: duration dependent response.

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7 Sd) along with Leydig cell nuclear area (LCNA) and radioimmunoassay of plasma levels of gonadotropins (FSH and LH), prolactin (PRL) and testosterone (T), activities of testicular, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were measured in mature rats of the Wistar strain following treatment with lithium chloride at a dose of 200 ug/100 g body wt/day for 7,14 and 21 days. A remarkable reduction in plasma levels of FSH (P less than 0.001), LH (P less than 0.05, P less than 0.01), PRL (P less than 0.05, P less than 0.001) and T (P less than 0.001) along with significant diminution in the activities of testicular delta 5-3 beta-HSD (P less than 0.001) and 17 beta-HSD (P less than 0.001) were observed following lithium treatment for 14 and 21 days. 21 days of treatment also resulted a marked degree of degeneration of ASg (P less than 0.05) and 7Sd(P less than 0.001) at stage VII but 14 days of treatment did not exhibited any significant effect on testicular gametogenesis. LCNA was decreased after lithium chloride treatment for 14 and 21 days (P less than 0.001). 7 days of treatment did not exert any notable result in the above parameters. The results of our experiment suggest that duration of lithium treatment is the critical factor for its adverse effects on testicular activity when the plasma levels of lithium remain within the therapeutic range. The possibility of an indirect action of lithium at the level of the testes is also discussed. Hence the data of our experiments have potential clinical implication.

Effects of gold on testicular steroidogenic and gametogenic functions in immature male albino rats.

The present study was undertaken to evaluate the effects of gold chloride, a metallic earth salt, on steroidogenic and gametogenic functions of testis in immature rats. Immature rats of Wistar strain, were injected (s.c.) with gold chloride at the dose of 0.3 mg and 0.5 mg/kg body weight/day for 26 days. All the treated animals along with the vehicle-treated controls were sacrificed 24 hours after last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, Delta5-3beta-hydroxysteroid dehydrogenase (Delta5-3beta-HSD) and 17-beta hydroxysteroid dehydrogenase (17-beta HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of testosterone (T) was measured by radioimmunoassay (RIA). Administration of gold chloride at a dose of 0.3 mg/ kg body weight for 26 days led to insignificant changes of testicular Delta5-3beta-HSD,17beta-HSD activities and gametogenesis along with plasma T. In contrast 0.5 mg gold chloride treatment for 26 days caused a significant increase in plasma T (p < 0.001) along with stimulation of testicular Delta5-3beta-HSD activity (p < 0.001) and 17beta-HSD activity (p < 0.001). Gametogenic activity exhibited a significant increase in the number of step 7 spermatids (7Sd) (p < 0.001) at stage VII of seminiferous cycle when compared to control. The results of our experiment suggest that gold chloride treatment might be associated with significant stimulatory effects on testicular activities. Furthermore, since hormonal changes, altered steroidogenic enzymes and gametogenic activities were evident to a specific dose of gold chloride treatment, our data may have some clinical implication on the stimulation of fertility.

Effects of lithium chloride on testicular steroidogenic and gametogenic functions in mature male albino rats.

The present study was undertaken to evaluate the effects of lithium, an antimanic drug, on steroidogenic and gametogenic functions of testis in the laboratory rat. Adult male rats of Wistar strain maintained under standard laboratory conditions (L:D, 14h:10h), were injected (S.C) with lithium chloride at the dose of 0.1 mg, 0.2 mg and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta hydroxysteroid dehydrogenase (17 beta-HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100 g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular delta 5-3 beta-HSD, 17 beta-HSD activities and gametogenesis. In contrast, 0.2 mg of lithium treatment for 21 days causes a significant reduction of plasma FSH (P less than 0.01), LH (P less than 0.001), PRL (P less than 0.001) and T (P less than 0.001) along with inhibition of testicular delta 5-3 beta-HSD activity (P less than 0.01) and 17 beta-HSD activity (P less than 0.001). Gametogenic activity does not exhibits any significant reduction in the number of preleptotene spermatocytes (PLSc) and midpachytene spermatocytes (mPSC) while significant reduction in the number of spermatogonia A (Asg) (P less than 0.01) and Step 7 spermatids (7Sd) (P less than 0.001) were observed at stage VII of seminiferous cycle when compared to control. The degree of detrimental effects of lithium on testicular activity became more prominent at the dose of 0.4 mg/100 g body wt. The results of our experiments suggest that lithium administration might be associated with significant adverse effects on testicular activities. Furthermore, since hormonal changes and altered gametogenic activities were evident when plasma lithium concentration was below or within the therapeutic range, our data may have some potential clinical implications.

Influence of adrenal cortex on testicular activity in the toad during the breeding season.

The aim of the present study was to determine the role of adrenals in gonadal activity in the male toad during the breeding season. Exogenous administration of corticosterone or metapyrone for 6 days inhibited adrenal delta5-3beta(delta 5-3 beta) hydroxysteroid (delta5-3beta-HSD) and testicular 17beta (17 beta) hydroxysteroid dehydrogenase (17beta-HSD) activities, decreased the serum levels of testosterone and inhibited spermatogenesis. When toads were treated with corticosterone a significant rise of serum corticosterone was noted while metapyrone treatment appeared to decrease serum corticosterone levels. It is concluded that adrenocortical hormone plays an indirect role in testicular activity in toads during the breeding season.

Effects of passive immunization against alpha-2u-globulin and supplementation with alpha-2u-globulin on serum gonadotrophins and testicular activity.

The purpose of the present study was to evaluate the effects of anti-alpha-2U-globulin on pituitary-gonadal functions in male rats. Adult male rats were given injections of anti-alpha-2u-globulin (1 mg/day) for 14 days, when they were killed 7 days after the last injection, serum levels of gonadotrophins and testosterone measured by radioimmunoassays, were less, testicular delta 3 beta- and 17 beta-hydroxy-steroid dehydrogenase (3 beta- and 17 beta-HSD) activities were suppressed, spermatogenesis was inhibited and serum level of alpha-2u-globulin was decreased in anti-alpha-2u-globulin treated rats. Administration of alpha-2u-globulin (1.5 mg/day) for 7 days to anti-alpha-2u-globulin treated rats reversed the 3beta-HSD and 17beta-HSD activities and serum levels of gonadotrophins, testosterone and alpha-2u-globulin, while spermatogenesis was restored to normal. The results indicate that changes in testicular steroidogenesis and spermatogenesis in rats after passive immunization against alpha-2u-globulin may be due to decrease in availability of endogenous alpha-2u-globulin.

Study on the activities of testes and accessory sex glands after losulazine treatment in rats.

Losulazine hydrochloride, an antihypertensive agent, was administered intraperitoneally to adult male Wistar rats in doses of 1, 2 and 5 mg/kg/day for 1 seminiferous epithelium cycle to determine its effects on testicular steroidogenesis, spermatogenesis and accessory sex gland function. Administration of low doses of losulazine (1 and 2 mg/kg) resulted in a significant elevation of the steriodogenic key enzymes activity along with significant depletion of cholesterol content in testicular tissue. In addition, a significant rise in acid phosphatase activity in testes and prostate, and fructose content in accessory sex glands was also observed after low doses of losulazine. However, treatment with a higher dose of losulazine (5 mg/kg) significantly reduced the activities of testicular steroidogenic enzymes and acid phosphatase, and the content of fructose in accessory sex glands. Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle and epididymal sperm count in all losulazine-treated rats revealed a persistant prominent detrimental change in spermatogenesis. The results of our present experiment demonstrate an adverse action of losulazine treatment on functional activities of testes and accessory sex glands in adult rats.

Effect of atenolol on cadmium-induced testicular toxicity in male rats.

Cadmium-induced stress adversely affects testicular activity and causes sympathetic stimulation. To investigate the effect of atenolol, a beta-adrenergic receptor blocker, on testicular androgen synthesis after cadmium treatment, adult Sprague-Dawley strain male rats were given a single sc dose of cadmium chloride 0.45 mg/kg BW. Animals were killed on day 3 after treatment. Adrenal weight, adrenal delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) activity, serum corticosterone, and brain noradrenaline were increased significantly while testicular delta 5-3 beta-HSD and 17 beta-HSD activities, serum testosterone, and accessory sex organs weight were decreased. Oral coadministration of atenolol at a dose of 2.0 mg/kg body weight for 3 days resulted in complete protection of adrenal delta 5-3 beta-HSD, testicular delta 5-3 beta-HSD, and 17 beta-HSD activities, adrenal weight, serum corticosterone, and serum testosterone when compared with cadmium-only group and there were no significant differences in these parameters from the vehicle control values. Simultaneous administration of cadmium and atenolol also protected brain noradrenaline content and reduced the rise of testicular cadmium concentration. All the parameters were similar to control levels in rats treated with atenolol alone. We conclude that atenolol may protect testicular androgen synthesis by inhibiting the action of noradrenaline on testicular Leydig cells and adrenocortical hyperactivity in cadmium-treated rats.

Testicular delta 5-3 beta-hydroxysteroid dehydrogenase in toad (Bufo melanostictus) following prolonged exposure to heat.

In contrast to our previous observation of increased activity of testicular delta5-3beta-hydroxysteroid dehydrogenase in toad with relation to the moderate rise of external temperature (40 degrees C), the present observation, however, shows a significant fall of this enzyme in the testis of toads exposed to a considerably high temperature (48 degrees C). The possible mechanism of action of heat on testicular steroid hormone synthesis has been discussed.

Hematologic and body fluid changes during simulated high altitude exposure in naproxen-treated rats.

Arterial blood oxygen saturation, body fluid and hematological parameters were studied in control, naproxen (a prostaglandin synthesis inhibitor)-treated control, altitude-exposed, and naproxen-treated altitude-exposed rats after intermittent exposure of 8 h/d for 6 consecutive days to a simulated high altitude of 6,100 m (barometric pressure 349 +/- 3 mmHg). Arterial blood oxygen saturation was reduced in altitude-exposed rats, but increased significantly to near control level in naproxen-treated rats. On the other hand, 2,3-diphosphoglycerate in erythrocytes increased in altitude-exposed rats, but naproxen prevented this increase. The red blood cell count, hemoglobin concentration and hematocrit ratio were reduced significantly in drug-treated altitude-exposed rats when compared to the altitude-exposed group (without drug). Red cell mass was increased in the altitude-exposed group in comparison with control. Both red cell mass and mean corpuscular volume of altitude-exposed rats were shifted towards the control value when they were treated with naproxen. Drug-treated high altitude-exposure reduced the thiocyanate space, intracellular fluid volume and total body water content compared to drug-treated control rats. On the other hand, thiocyanate space and total body water content were increased significantly in drug-treated control rats in comparison with the control group.

Antitesticular effect of copper chloride in albino rats.

Copper chloride treatment adversely affects testicular activity in albino rats. To investigate its antitesticular effects mature (120 days) Wistar strain albino rats were treated intraperitoneally (i.p.) with copper chloride at doses of 1000, 2000 and 3000 micrograms/kg body weight/day for 26 days. Significant reduction of testicular and accessory sex organs (seminal vesicle, ventral prostate) weight, along with inhibition of testicular delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity and reduction in plasma testosterone level, were observed at the doses of 2000 and 3000 micrograms/kg body weight/day. The degree of inhibition in all the parameters were increased with the increase of dosage. But no significant change was observed in the above parameters when the animals were treated with 1000 micrograms/kg body weight/day dose. This suggests that copper produces a suppressive influence on male reproductive activity, mainly on testicular weight and steroidogenesis and accessory sex organ weight in a dose-dependent manner.

Protection of adrenocortical activity by dietary casein in ether anaesthetized rats.

Adrenal delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activity and serum corticosterone level were significantly higher in rats fed with 5% casein or 4% albumin diets after 1 hr of ether anaesthetic stress as compared to the controls, 5% casein and 20% casein (equivalent to 4% albumin) respectively. Ether anaesthesia to 20% casein fed rats caused no change in adrenal delta5-3beta-HSD activity and serum corticosterone level when compared with controls fed 20% casein diet. The results suggest that high milk protein diet may prevent acute stress effects by protecting adrenocortical activity. The present investigation opens up a new area of management of stress.

Effect of lithium chloride on spermatogenesis and testicular delta 5-3 beta, 17 beta-hydroxysteroid dehydrogenase activities in the 'antiserum to luteinizing hormone' treated toad (Bufo melanostictus).

Activities of delta 5-3 beta- and 17 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD and 17 beta-HSD), Leydig cell nuclear area (LCNA) and spermatogenesis in the testis were observed after injection of lithium chloride in the 'antiserum to luteinizing hormone (LH)' treated toad. A significant decrease in the activities of steroidogenic enzymes, LCNA and spermatogenesis were noticed after the injections of 'antiserum to LH' to toads. Further decrease in the activities of the above parameters was observed in the lithium chloride--'antiserum to LH' treated toad. It is suggested that lithium chloride may inhibits testicular function without modulating the pituitary activity.