Effect of megestrol acetate on the genital organs & fertility of male rats

The effect of the oral administration of megestrol acetate (MA; 17 alpha-acetoxy-6-dehydro-6-methylprogesterone) for 30 days at a dose of 40 mg/kg body weight/day on the genital organs and fertility of male rats was studied. MA had no effect on spermatogenesis or the fertility of the animals. However, the weights of the genital organs were significantly reduced (p less than .05) and pituitary gonadotropin levels were significantly increased (p less than .01). These alterations were reversed after cessation of treatment. Although MA and testosterone propionate each increase seminal vesicle weight, their combined administration significantly decreased seminal vesicle and ventral prostate weight (p less than .01). The significance of the results are discussed.     

Extremely low-frequency magnetic fields can impair spermatogenesis recovery after reversible testicular damage induced by heat

Male infertility is often related to reproductive age couples experiencing fertility-related issues. Men may have fertility problems associated with reversible testicular damage. Considering that men have been increasingly exposed to extremely low-frequency magnetic fields generated by the production, distribution and use of electricity, this study analyzed whether 60?Hz and 1?mT magnetic field exposure may impair spermatogenesis recovery after reversible testicular damage induced by heat shock using rats as an experimental model. Adult male rats were subjected to a single testicular heat shock (HS, 43?°C for 12?min) and then exposed to the magnetic field for 15, 30 and 60?d after HS. Magnetic field exposure during the spermatogenesis recovery induced changes in testis components volume, cell ultrastructure and histomorphometrical parameters. Control animals had a reestablished and active spermatogenesis at 60?d after heat shock, while animals exposed to magnetic field still showed extensive testicular degeneration. Magnetic field exposure did not change the plasma testosterone. In conclusion, extremely low-frequency magnetic field may be harmful to fertility recovery in males affected by reversible testicular damage.     

Decidualization in rats given 5alpha-dihydrotestosterone or its propionate neonatally.

In Experiment 1, female rats were given a single subcutaneous injection of 1.25 mg 5alpha-dihydrotestosterone (DHT) or its propionate (DHTP) on day 5 of postnatal life. All of them showed regular estrous cycles as adults like untreated control animals. At about 60 days of age, the rats were ovariectomized and given 7 daily injections of 2 mg progesterone (P) plus 0.2 mug estradiol-17beta (ED). Uterine trauma applied on the 4th day of P-ED injections resulted in well developed deciduomata in all animals by the day after the last injection. This made a sharp contrast to the failure of female rats receiving testosterone propionate (TP) neonatally to give a positive response under similar experimental conditions (Takewaki and Ohta, 1974). The mean weight of traumatized horns was significantly larger in DHTP-treated rats (but not in DHT-treated rats) than in controls. In Experiment 2, rats were ovariectomized on day 4 and given a dose of 1.25 mg DHT or DHTP on day 5. Controls were ovariectomized on day 4 but not given any steroid on the next day. A series of 7 daily injections of 2 mg P plus 0.2 mug ED was started at about 60 days of age, after the animals had received 3 daily injections of 0.2 mug ED or 30 daily injections of 0.1 mug ED. Incidence of deciduomata following uterine traumatization was markedly lowered only in animals treated with DHTP neonatally and given 0.1 mug ED for 30 days as adults, no significant differences being found in both incidence and size of deciduomata among the other groups. It was suggested that the effects of neonatal steroid administration on uterine responsiveness in adulthood are specific to the steroid. The previous conclusion that persistent estrus in androgen-sterilized rats plays a part in the reduction of uterine responsiveness was confirmed. An exposure of rats to estrogen for a prolonged postpuberal period was without effect, unless the animals had received enough androgen neonatally.     

Effect of molybdenum supplementation onN-nitroso-N-methylurea-induced mammary carcinogenesis and molybdenum excretion in rats

Molybdenum (Mo) supplementation reduces the incidence of nitrosamine-induced tumors in the esophagus and forestomach of laboratory animals, and the incidence of mammary cancer in female rats induced byN-nitroso-N-methylurea (NMU). The present study was conducted to evaluate the effect of graded amounts of Mo on NMU-induced mammary carcinogenesis, and on the excretion of Mo and copper (Cu). Female Sprague-Dawley rats aged 5 wk were givenad libitum a low-Mo (0.026 mg/kg) diet and deionized water. After 15 d, a single SC injection of 50 mg NMU/kg body wt was administered to each of 30 rats in groups 2–5. Eight rats in group 1 served as untreated control. One week after the carcinogen treatment, 0.1, 1.0, or 10 mg Mo from sodium molybdate were added to each liter of drinking water for groups 3, 4, and 5, respectively. Groups 1 and 2 did not receive any Mo supplementation. After the rats had been Mosupplemented for 38, 67, and 85 d, 48-h urine and fecal samples were collected from the same 48 rats, and Mo and Cu were determined. Molybdenum seemed to have little effect on Cu excretion. At each time interval, animals fed 0 or 0.1 mg Mo/L excreted more Mo in feces than in urine, whereas rats fed 1 and 10 mg Mo/L water excreted more Mo in urine than in feces, which indicates that Mo absorption was not easily saturated as the amount of Mo increased. However, the liver became saturated with Mo when 0.1–1 mg Mo/L was fed. The total number of palpable tumors per group 101 d after NMU administration was 109, 115, 101, and 81, and the total carcinomas per group were 92, 96, 86, and 65 for the animals in groups 2–5, respectively. The results indicate that supplemental Mo in the amount of 10 mg/L of drinking water inhibited mammary carcinogenesis.     

Clinical and Laboratory Findings in a Trial of Norgestrel,a Low-dose Progestogen-only Contraceptive

Norgestrel, a progestogen-only oral contraceptive, was given continually at a dose of 75 μg/day to 144 women of proved fertility. It was an efficient contraceptive with a failure rate of 2·1% (assessed by the “life-table” method) within the first 12 cycles and 3·6% within the first 30 cycles (or 2·0 conceptions per 100 woman-years when assessed by the Pearl index). The overall conception rate for the entire trial period was 2·1% and 1·3 pregnancies per 100 woman-years respectively. Norgestrel caused a high proportion of irregular and generally short bleeding intervals, about one-fifth of the cycles lasting less than 17 days. This irregularity appeared to be due to individual variance in cycle length between women rather than that between their successive cycles. No confirmed instances of thromboembolism were observed. Norgestrel apparently exerts its contraceptive action by several mechanisms: reduction in the sperm penetrability of the cervical mucus and an impairment of luteal function appear important. The serum concentrations of cholesterol and globulin were significantly reduced in women taking norgestrel. Preliminary observations suggest that on discontinuing the medication fertility is promptly restored. Of the 144 women originally enrolled 57 (40%) withdrew for reasons connected with the method before completing 30 months on trial, over half of them because of the irregular menstrual pattern. Nonetheless, in view of its main clinical and laboratory characteristics and simple mode of administration, norgestrel appears to be a useful alternative to the combined type of pill for women unsuitable for, or unable to tolerate, oestrogen-containing preparations.     

Factors involved in the maintenance of luteal function in the pseudopregnant rat

Some data on a new antispermatogenic and antifertility compound, DL-6-(N-alpha-pipecolinomethyl)-5-hydroxy-indane maleate (PMHI) are presented. It was found that PMHI depressed testicular weight and interfered with spermatogenesis and fertility in the male rat. At equal doses, by weight, PMHI caused a greater reduction in testicular weight than WIN 18446, nitrofurazone, methallibure, and diethylstilbestrol, but lesser reductions in seminal vesicle and ventral prostate weights than were obtained with the 2 antigonadotropic compounds, methallibure and diethylstilbestrol. The data obtained in the experiments indicate that administration of PMHI causes sterility in male rats as a consequence of antispermatogenic activity. At low dosage levels (3 mg/kg), the action was reversible, but animals given 6.25 mg/kg/day or more remained sterile for 19 weeks following the treatment period. Doses of the compound which were effective in the male rat did not interfere with normal estrous cycles or fertility when administered to female rats.     

Antifertility effect of busulfan and DL-6-(N-2-pipecolinomethyl)-5-hydroxy-indane maleate (PMHI) in coyotes (Canis Latrans )

Antifertility effects of busulfan were evaluated using adult coyotes. In addition, antifertility effects of PMHI were evaluated in adult males. Adult males and females were alloted randomly to the following treatments: (1) untreated control, (2) a single oral dose of 3 mg busulfan/kg of body weight (BW) or (3) two oral doses of 3 mg busulfan/kg BW given nine days apart. The untreated males were used as controls in both experiments. Additional male coyotes were allotted randomly to PMHI treatments as follows: (1) a single oral dose of 2 mg PMHI/kg BW, or (2) two oral doses of 1 mg PMHI/kg BW given seven days apart. Blood samples were taken from females and serum analyzed for progesterone by radioimmunoassay. Males were hemicastrated (left testicle) 30 days after onset of treatment. The right testicle was removed 30 days later. Testes and epididymides were fixed in 10% buffered formalin and prepared for histologic examination. For females developing corpus luteum (CL), the maximum peak progesterone concentration for those given two doses of busulfan was less (P<0.05) than that for untreated controls and single-dose females (16.9, 22.4 and 26.3 ng/ml, respectively). The double treatment of busulfan prevented more females (4 of 10) from developing CL (P<0.08) than controls (0 of 7) or single-dose females (1 of 9). None of the busulfan-treated male coyotes had histologic evidence of spermatogenesis 60 days after the onset of treatment. The oral dose or doses of PMHI did not result in complete degeneration of seminiferous tubules. Busulfan given orally did not cause any adverse reactions, but orally administered PMHI often induced vomiting within 18 min after treatment. We conclude that busulfan is capable of affecting male and female reproductive parameters, but PMHI appears to have little effect on spermatogenesis in coyotes when given orally in a single- or a double-dose.     

Effects of Malva viscus conzattii Greenm flower extract on testicular function of the house rat Rattus rattus Rufescens & the gerbil Meriones hurrianae Jerdon: a biochemical study

Extract of the flower Malva viscus conzattii (M. conzattii) was administered at a dose of 25/50 mg/day/animal to 30 healthy adult male gerbils and 30 adult male house rats to determine its effect on fertility. After 25 days' treatment fin l body weight, and the weights of testes, epididymides, seminal vesicles, and adrenal glands were measured. Testis, epididymides, and seminal vesicles were prepared for histological examination and total protein, RNA, sialic acid, and alkaline phosphatase activity were determined. Quantitative estimation of cholesterol was also made. While overall body weight remained stable during treatment, testicular weight in both animals was drastically decreased. A complete spermatogenic arrest in the testes was evident in house rats treated with 50 mg/day for 20 days and in the gerbil treated with 25 mg/day for 25 days. The seminiferous tubules showed marked degeneration, lined by 1 or 2 cell layers. Epididymides showed degenerative changes as well. RNA contents of the testes, epididydmides, and seminal vesicles of treated anials were significantly lowered as was sialilc acid content. Total cholesterol was increased significantly. M. conzattii causes an effective inhibition of spermatogenesis in gerbils and house rats in 25 states and induces infertility.     

Prevention of chronic alcohol and nicotine-induced azospermia,sterility and decreased libido,by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats

Excessive long term consumption of alcohol and nicotine have serious detrimental effects upon the libido, fertility, and sperm count in male species. The present work describes the beneficial effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linneaus, the phyto-chemical isolation, spectroscopic elucidation, and multifarious biological activities of which have recently been reported by the authors. The BZF moiety has been reported to increase libido, sperm count, and sexual fertility in 2 years old male rats at 10 mg/kg, po dose, in the one of our previous studies. Presently, the BZF moiety has been evaluated against chronic ethanol- and nicotine-induced decrease in libido, sexual fertility and mating efficiency in healthy male rats. The male rats were given ethanol (3 g/kg, po) A, nicotine (2 mg/kg, sc) N, alcohol-nicotine combinations (AN) alone, and also with 10 mg/kg po dose of BZF (concurrent administrations). These treatments were given for 30 days. At the end of treatments, it was observed that rat groups A, N, and AN had no libido (evaluated by mounting behaviour), declined sperm count, and consequently no mating efficiency or fertility (upon pairing with pro-estrus female rats). However, the rats which were given 10 mg/kg BZF along-with nicotine (NP group), alcohol (AP group), and alcohol-nicotine combination (ANP) exhibited significant libido-oriented mounting behaviour, increased sperm count (significantly comparable to the control group), and increased fertilization potential. The rats having decreased sperm count, libido and fertilization potential due to chronic administration of alcohol, nicotine and alcohol-nicotine combinations, i.e., rats of A, N, and AN groups were again subdivided and were given 10 mg/kg BZF for 7 days. This treatment confirmed that BZF speeds up the restoration of sexuality in rats upon cessation of the administration of substances like alcohol, nicotine and alcohol-nicotine combinations, which have severe detrimental effects upon male sexuality, fertility and vigour. BZF, the strongest inhibitor of aromatase enzyme, when administered concurrently with substances like alcohol and nicotine restores sexual virility, libido and vigour in male rats by maintaining the blood-testosterone levels to be high.     

Trichlormethine hydrochloride and correlation of its mutagenic and toxic effects on male germ cells in mice.

The genetic effect of the cytostatic trichlormethine hydrochloride (TS-160 Spofa) was assessed after a 1-week administration using the dominant lethal mutation test (DLM) and the sperm abnormality test. The dosage was 0.5 mg/kg for 7 consecutive days, an equivalent of the human therapeutic dosage. Simultaneously, the cytostatic's direct toxic effect on male sex organs was assessed. TS-160 carries a genetic risk for the postmeiotic stages of spermatogenesis (DLM) and is responsible for interference in the morphology of sperm heads through its action on spermatocytes. The toxic effects of TS-160 were found to influence the body weight of mice (days 4-25 after administration), to reduce the relative weight of the testes (days 18-25 after administration), to damage spermatogenesis in the seminiferous tubules (spermatids), to be responsible for an appearance of multinucleate cells in the epididymides, and for an increased rate of abnormality of the heads of fully mature spermatozoa. Our findings stress the need to separate the cytotoxic effects from genetic effects so as to avoid false positives, especially in the test for head abnormalities, and also in the assessment of the fertility of male animals or fertilization of females mated with treated males.     

The effect of cryptorchidism and subsequent orchidopexy on testicular function in adult rats

Cryptorchidism for 28 or 10 days resulted in a severe disruption of spermatogenesis (assessed histologically or by fertility tests), Sertoli cell function (assessed by seminiferous tubule fluid production after efferent duct ligation, ABP levels, binding of 125I-labelled FSH to testis homogenates and serum FSH levels) and Leydig cell function (assessed by serum LH and testosterone levels, in-vitro testosterone production, binding of 125I-labelled hCG). Orchidopexy after 28 days of cryptorchidism resulted in a poor recovery of spermatogenesis since the majority of tubules were lined by Sertoli cells and a few spermatogonia. No recovery occurred in the indicators of Sertoli and Leydig cell function. Orchidopexy after 10 days of cryptorchidism also resulted in a poor recovery of spermatogenesis, with a few animals showing partial recovery after 6 months. No recovery occurred in seminiferous tubule fluid production but partial recovery occurred in ABP content and production rate. Serum FSH, LH levels and in-vitro testosterone production by the testis remained elevated and did not change from the values found during cryptorchidism. Fertility testing at 6 months revealed a small number of rats in which fertility was restored although the number of embryos was lower than in controls. In this group of animals there was a significant improvement in a number of indicators of Sertoli cell and Leydig cell function. These data provide further evidence to link the changes in Sertoli cell and Leydig cell function to the germ cell complement present in the testis.     

Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro.

Pancreatic islet cell vacuolization, hyperglycemia, and glucose intolerance develop in rats after oral administration of cyproheptadine (CPH). In order to determine whether these effects were associated with abnormal insulin secretion, pancreas segments from CPH-treated and control rats were compared for their ability to secrete insulin in response to several stimuli. Oral administration of CPH (45 mg/kg/day) to rats for 1 or 8 days inhibited glucose-mediated insulin secretion from pancreas segments obtained 3 and 24 hr after the last dose of the drug. Insulin secretion had returned to normal by 48 hr after drug administration. Intraperitoneal administration of the drug was less effective than oral administration in inhibiting in vitro insulin secretion. Other stimuli for insulin secretion (tolbutamide, glucagon, L-leucine, and dibutyryl 3',5'cyclic AMP), like glucose, were incapable of releasing normal amounts of insulin from pancreas segments of CPH-treated rats. CPH and a metabolite, desmethyl-CPH, inhibited glucose-stimulated insulin secretion when added in vitro to pancreas segments from control rats. This suggests that the inhibition of insulin secretion in pancreas segments taken from animals treated with CPH could be due, at least in part, to the presence of drug and its metabolite in the tissue. A previously observed reduction in the pancreatic content of insulin in CPH-treated rats may also contribute to the abnormal insulin release in animals given the drug.     

The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of warfarin in rats.

Significant pharmacokinetic/pharmacodynamic interactions between various herbal products and warfarin have recently been reported. The aim of this study was to determine whether concomitant treatment of rats with Kan Jang (a standardized fixed combination of extracts from Andrographis paniculata and Eleutherococcus senticosus) and warfarin would lead to an alteration in the pharmacological effects of warfarin. Each day for 5 days a group of animals was treated orally with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active principle andrographolide (a daily dose some 17-fold higher than that recommended for humans): the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml) was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration and blood samples taken. The concentration of warfarin in blood plasma was measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm. Prothrombin time in blood plasma was measured using thromboplastin reagent. The concomitant application of Kan Jang and warfarin did not produce significant effects on the pharmacokinetics of warfarin, and practically no effect on its pharmacodynamics.     

Time-course of changes in blood glucose and ketone bodies, plasma lipids and liver fatty acid composition in streptozotocin-diabetic male rats.

Male rats were given streptozotocin (100 mg/kg) by intraperitoneal injection. Groups of control and streptozotocin-treated animals were sacrificed at daily intervals for 4 days after injection. Over this period, treated rats lost weight continuously while control animals progressively gained weight. Within 24 h of treatment blood glucose and plasma free fatty acids were raised to levels which were sustained for the remainder of the experiment. After 48 h blood ketone bodies, plasma cholesterol and triglycerides were maximally raised and liver glycogen and blood lactate similarly lowered. The percentage composition of major fatty acids in liver lipids was unchanged until 4 days after treatment when there were significant increases in the proportion of oleate and linoleate and reductions in stearate and arachidonate. The data confirm that streptozotocin induces a rapid and sustained diabetes. It is suggested that metabolic experiments, in streptozotocin-diabetic rats, may be performed 48 h after treatment.     

Effects of various doses of testosterone propionate on intratesticular and plasma testosterone levels and maintenance of spermatogenesis in adult hypophysectomized rats.

Adult hypophysectomized rats were maintained on different regimens of testosterone propionate (TP) treatment for 27 days (0.2, 0.4, 0.6 and 1 mg/day) and autopsied 16 hours after the last injection. Blood samples were taken, sex organs were weighed and one testis from each animal was fixed in Bouins fluid for histologic analysis. The other testis and blood were used for testosterone (T) determinations. Both testicular and plasma T were below detectable levels in hypophysectomized control rats. The plasma T level showed a dose response relationship with increasing dose of TP but such was not the case for intratesticular T concentrations. Qualitative and quantitative evaluation of testis sections showed that spermatogenesis was incomplete in rats receiving 0.2 mg TP/day characterized by the absence of step 15 to 19 spermatids, degeneration of some pachytene spermatocytes and a significantly lower yield of B type spermatogonia. Analysis of testis sections from animals treated with 0.4 to 1 mg TP/day showed complete maintenance and maturation of pachytene spermatocytes, meiosis and spermiogenesis. However, even with the highest dose of TP (1 mg/day) the total yield of B type spermatogonia was only about 58% of the intact controls. It is concluded that at least 0.4 mg/day of exogenous TP is essential for qualitative maintenance of spermatogenesis in hypophysectomized rats with an intratesticular T concentration of 17 to 18 ng/gm testis.     

Insensitivity of the coyote testis to orally administered cadmium

A study was conducted to evaluate cadmium as an oral antifertility agent in the coyote. Adult wild male coyotes were treated with cadmium chloride (CdCl₂) when testicular tissues were in both seasonally regressed and active states. One group of seven animals received individual oral doses of CdCl₂ at 12 mg/kg of body weight during the stage of complete testicular regression; another group similarly received 24 mg/kg. An additional group of six animals was used as untreated controls. Unilateral testicular ablations were carried out at 60, 120 and 240 days post-treatment. No histopathological changes were noted at either treatment level or at any testing period. Testicular tissue taken at the 240 day period revealed normal spermatogenesis. Testicular tissue was removed at 1, 8, 13, 21, and 30 days after the coyotes had received 24 mg/kg of CdCl₂ orally during the stage of active spermatogenesis. Histological examination of this tissue revealed no pathological changes.     

Lack of cardiac alpha 1-adrenoceptor involvement in ethanol-induced cardiac hypertrophy

The development of cardiac hypertrophy was examined in rats given ethanol in a nutritionally adequate, liquid diet mixture, by intubation, in severely intoxicating doses at 8-h intervals for up to 96 h, alone or in combination with prazosin. Other groups of rats received isocalorically paired quantities of maltose-dextrin. Adrenal glands of rats receiving ethanol were larger than those from control animals. Prazosin did not affect this measure. In contrast, concurrent treatment with prazosin enhanced the loss of medullary catecholamines and noradrenaline from hearts of rats given ethanol, while it had no such effects in controls. Reflecting these changes, excreted quantities of catecholamines were markedly increased in rats given ethanol and prazosin. Hearts of animals given the combined treatment of ethanol and prazosin showed cardiomegaly at 24 h, when there was an increase of about 20% in proportional heart weight, an increase that persisted through the remaining 3 days of the study. At 48 h, hearts of animals given prazosin and ethanol were heavier than those given ethanol alone. A significant correlation between catecholamine excretion and the development of cardiac hypertrophy was identified. The results of the study show that prazosin can enhance effects of ethanol on the peripheral sympathetic nervous system. Moreover, the results suggest that postsynaptic alpha 1-adrenoceptor stimulation in the heart is not an important contributor to ethanol-induced cardiomegaly.     

Reduction of carcinogen-induced breast cancer in rats by an anti-fertility drug

The DMBA (dimethylbenz[a]anthracene)-induced mammary cancer systems seemed to be an ideal model for the study of the influence of oral contraceptives (OCs) on endocrine-related cancers. Groups of 20 female Sprague-Dawley rats, age 40-45 days, weight approximately 150 g, were given 3.0 or 0.3 mg of crystalline Enovid suspended in 1 ml of sesame oil per dose for 45 days. The controls consisted of a group of 20 rats given a single dose of 15 mg of DMBA, of 2 groups of 10 rats administered daily doses of 3.0 and 0.3, respectively, of Enovid for 45 days, and of 1 group of 20 rats on sesame oil. In addition to these 6 groups, 3 additional sets of 5 rats each were fed 3.0 or 0.3 mg Enovid per rat, or 0.3 mg Enovid plus the subsequent single dose of 15 mg DMBA. The animals were weighed weekly and thoroughly examined for the appearance of mammary tumors or other grossly apparent lesions. The dosage of Enovid was selected on the basis of preliminary experiments. With doses of 0.005 mg per 150 g rat the estrus cycle was usually but not always arrested 5 days after the treatment began. At doses of 0.05 and 0.5 mg the cycle was interrupted 3-5 days and at 1 day later. In the final studies with doses of 0.3 and 3.0 mg, the microscopic examination of the smears indicated that the estrus cycle was effectively halted in all rats throughout the Enovid, or Enovid plus carcinogen feeding period but returned to normal shortly after the cessation of Enovid administration. DMBA failed to restore the estrus cycle suggesting that Enovid exerts a pronounced effect on the endocrine system. A single dose of 15 mg DMBA yielded an increasing incidence of mammary tumors which reached 100% after about 6 months. The multiplicity also rose and reached an average of 5.8 masses per rat at the end of the planned experiment period of 9 months. Histopathologic examination of the tumors indicated that there were several types, and even the same tumor nodule exhibited areas of varying morphologic aspect. Administration of the lower level of Enovid tended to inhibit slightly the incidence of mammary cancer. Of the 20 sesame oil control animals, only 1, killed after 237 days, had a large fibroadenoma.     

Effects of stress and of amphetamine on passive avoidance conditioning in rats

This study examined the effects of immobilization stress combined with water immersion (ICS) and/or amphetamine (AM) on different memory phases in the passive avoidance task in rats. The performance of rats was evaluated in the retention tests 24 and 48 h after a single acquisition trial. ICS exposure lasting 1 h impaired retention of the learned avoidance response if applied 2 to 4 h before or immediately after training. The stressor did not affect retrieval if presented 5 or 2 h before the retention test. AM was used i.p. at the dose of 8 or 1 mg/kg. Neither 8 mg AM administered 4 h before nor 8 or 1 mg doses given after training did not impair the retention performance in unstressed rats. The 1 mg AM prevented the impairment of retention in animals exposed to the stressor 3 or 4 h before training but had no effect when the stronger impairment was induced by ICS 2 h before training. However, when given 1 h before retention testing, 1 mg AM attenuated even the severe impairment induced by the pre-training stressor exposure. Our results suggest that ICS impairs primarily the early phase of memory consolidation and a low dose of AM can prevent this effect.     

Hormonal effects of lead acetate in the male rat: mechanism of action

Environmental exposure to toxic levels of lead occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. Using a rat model, we previously reported that dietary exposure to lead resulted in suppressed spermatogenesis and testosterone levels without significant changes in luteinizing hormone (LH). In this study, to identify more specifically the site of lead's toxic actions on the hypothalamic-pituitary-testicular axis, the response of lead-treated male rats as compared to control animals to naloxone, gonadotropin-releasing hormone (GnRH), and LH stimulation was studied. Three groups of 52-day-old Wistar rats were allowed access to either deionized distilled water containing no lead acetate or a 0.3% lead acetate solution for 30 days. In each study group, 10 control and 10 lead-treated animals were anesthetized prior to cardiac puncture and collection of serum for the measurement of lead level and baseline LH (Groups I and II) or testosterone levels (Group III). In Group I, 20 min after an i.p. injection of naloxone (1.5 mg/kg/BW), the animals were killed by decapitation, and serum was collected for LH measurement. Thirty minutes after an i.p. injection of GnRH (100 ng/100 gm BW), Group II animals were killed by decapitation, and serum was collected for LH. Sixty minutes after an injection of LH (100 mg/100 mg BW), serum was collected from Group III animals for testosterone measurement. All control animals and lead-treated animals consumed similar volumes of water. Control animals had undetectable levels of lead in their blood. Lead-treated animals had mean blood lead values of 30 micrograms/dl +/- 5 micrograms/dl.(ABSTRACT TRUNCATED AT 250 WORDS)