Effects of a 5-day treatment with the UV-filter octyl-methoxycinnamate (OMC) on the function of the hypothalamo-pituitary-thyroid function in rats

Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an "endocrine active chemical" (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary-thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17beta-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium-iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5'deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels.     

Hormones of the hypothalamo-pituitary-gonadal axis in drug discrimination learning.

More than 30 years ago, T-maze studies with progesterone indicated that sex hormones have the potential to act as a discriminative stimulus in rats. Despite these early positive findings, the interest in discriminative stimulus properties of sex hormones remained low; few studies were dedicated to the investigation of discriminative stimulus properties of hypothalamo-pituitary-gonadal axis hormones (i.e., LHRH, LH/FSH, sex steroids). Nevertheless, the few studies that were published showed some interesting, and often sex-dependent results. Applying various methodologies (T-, or Y-maze, two-lever drug discrimination, taste aversion procedures), it was found that not only progesterone but also the two other principal sex steroids estradiol and testosterone can serve as discriminative stimuli in rodents. In addition to these gonadal hormones, the hypothalamic peptide LHRH (having a key role in the neuroendocrine regulation of steroid release from the gonads) appears to generate discriminative stimulus properties. Interestingly, recent (but preliminary) studies in postmenopausal women suggest that estradiol (and possibly progesterone) may also function as a discriminative stimulus in human subjects.     

Atrazine and the hypothalamo-pituitary-gonadal axis in sexually maturing precocial birds: studies in male Japanese quail.

The herbicide atrazine is a putative endocrine disruptor. The present studies investigated the effects of atrazine in male Japanese quail during sexual maturation. Atrazine was administered for two weeks in the diet or systemically to birds under long photoperiods. Atrazine had no effect on mortality but depressed both feed intake and growth (average daily gain [ADG] in g/day) at dietary concentrations of 1000 ppm. Atrazine in the diet at 10 ppm, but at no other concentrations, increased testes weight and gonadal-somatic-index and decreased the seminiferous tubule diameter-to-testis weight ratio. However, there were no effects on absolute tubule diameter, relative stage of testicular development, or the presence of a lumen. Atrazine in the diet at 1000 ppm increased circulating concentrations of testosterone but this effect was not observed consistently in all studies. Dietary atrazine at 10 ppm increased circulating concentrations of estradiol. Moreover, in one study, atrazine at 1000 ppm in the diet decreased circulating concentrations of luteinizing hormone. Atrazine administered systemically exerted no effect on indices of growth or reproduction. Atrazine did not mimic the effects of either estradiol or tamoxifen in male quail; thus, atrazine did not exhibit overt estrogenic or anti-estrogenic activity. Conversely, atrazine augmented the effects of testosterone and estradiol on testis regression, presumably by increasing the negative-feedback effects of these sex-steroids on follicle stimulating hormone secretion. It is concluded that atrazine up to 1000 ppm in the diet may exert some effects on reproductive development in sexually maturing male birds, but these are inconsistent and modest.     

Effects of 5-day styrene inhalation on serum prolactin and dopamine levels and on hypothalamic and striatal catecholamine concentrations in male rats

In several studies a hypersecretion of the pituitary hormone prolactin (PRL) in styrene-exposed workers has been described. This should cause reproductive problems like oligomenorrhea, secondary amenorrhea and reduced fertility [Arfini et al. (1987) J Occup Med 29:826-830, Bergamaschi et al. (1996) Neurotoxicology 17:753-760, Mutti and Smargiassi (1998) Toxicol Ind Health 14:311-323]. Secretion of PRL is tonically inhibited by the catecholamine dopamine (DA), which is released from hypothalamic neurons. It has been suggested that the activity of the enzyme dopamine-beta-hydroxylase (DBH) in the serum is a peripheral marker of central dopaminergic function. A slight reduction of such enzymatic activity was observed in styrene-exposed workers, which was associated with hypersecretion of PRL. To further investigate the putative effects of styrene on PRL release, male rats were exposed to styrene vapors (645, 2150 and 6450 mg/m(3)) for 6 h/day on 5 consecutive days. Animals were killed either directly following the last exposure (immediate group) or after a recovery period of 24 h (recovery group). Serum PRL and DA levels were measured by radioimmunoassay. Concentrations of catecholamines and their metabolites in the striatum and mediobasal hypothalamus (MBH) were determined by high performance liquid chromatography with electrochemical detection. Neither in the immediate nor in the recovery group were any statistically significant changes of serum PRL levels observed. Likewise, concentrations of catecholamines and their metabolites in the striatum and MBH remained unaffected. We conclude from these data that styrene, even at very high concentrations, has no adverse effects on the neuroendocrine mechanisms regulating PRL release and DA levels in the brain. With the limitations inherent in any animal model, we suggest that our data indicate that styrene also has no adverse neuroendocrine effects in humans.     

Effects of repeated morphine administration on copulation and on the hypothalamic-pituitary-gonadal axis of male rats.

Adult male rats were administered morphine twice a day for 45 days and the effects of morphine on the copulation rate, the weight of various organs, and on the hypothalamic-pituitary-gonadal axis were examined. Morphine administered rats showed a loss of weight, hypertrophy of the adrenals, decreased weight of accessory sex organs, low sperm count, and decreased copulation rate. The contents of the luteinizing hormone releasing hormone in the hypothalamus and the luteinizing hormone in the pituitary remained unchanged. Serum luteinizing hormone and testosterone levels decreased, but serum follicle-stimulating hormone levels increased. These results suggest that morphine inhibits the hypothalamic-pituitary-gonadal axis and causes a diminution in the number of fertilizations of the partner females.     

Effects of beta-phenylethylamine on the hypothalamo-pituitary-adrenal axis in the male rat

beta-Phenylethylamine (PEA) is a trace neuroactive amine implicated in the regulation of the hypothalamic-pituitary-adrenal (HPA) response to stress. To test this hypothesis, effects of subchronic levels of PEA (50 mg/kg/day treatment for 10 days) on the corticotroph function were studied. PEA treatment induces: (i) a significant increase of corticotrophin releasing hormone (CRH) immunoreactivity in the median eminence (ME), as measured by semi-quantitative immunofluorescence labeling techniques, (ii) a significant increase in CRH mRNA levels in paraventricular nuclei, as detected by in situ hybridization, and (iii) an increase in plasma adreno-corticotrophin hormone (ACTH) and corticosterone levels in responses to stress. PEA treatment has no effect on the number of binding sites and on the dissociation constant of the glucocorticoid receptors in any structure studied. Results of the dexamethasone suppression test were similar in PEA- and saline-treated rats. Taken together, these results suggest that PEA treatment stimulated the HPA axis activity levels directly via the CRH hypothalamic neurons, without altering the negative feed back control exerted by the glucocorticoids.     

Effects of 5-day styrene inhalation on serum LH and testosterone levels and on hypothalamic and striatal amino acid neurotransmitter concentrations in male rats

The volatile chemical styrene may impair male fertility. Testicular testosterone (T) production is controlled by the hypothalamic/pituitary/gonadal axis. From the mediobasal hypothalamus (MBH), gonadotropin-releasing hormone (GnRH) is released, which stimulates luteinizing hormone (LH) secretion from the pituitary, which in turn enhances T production. GnRH release is controlled by glutamate (GLU) and gamma-aminobutyric acid (GABA). GLU and GABA neurons are regulated by T. Thus, reduced fertility of styrene-exposed male workers may result from altered GLU/GABA neurotransmission, causing insufficient GnRH, LH, and T secretion. Therefore, we compared LH and T levels of male rats that have inhaled styrene (0, 150, 500, 1500 ppm for 6 h on 5 consecutive days) to GLU and GABA concentrations in the MBH and striatum. Animals were killed directly following the last exposure (immediate group) or after 24 h (recovery group). No suppression of LH or T levels was observed after styrene inhalation. LH levels of the immediate groups with 500 or 1500 ppm exposure were slightly but significantly elevated. Hypothalamic GLU and GABA concentrations remained unchanged. Increased striatal GABA concentrations were determined in recovery groups with 500 or 1500 ppm exposure. Striatal GLU concentrations remained unaffected. Thus, we demonstrate slightly increased LH and T levels in styrene-exposed male rats after inhalation of the two higher doses. This effect did not correlate with hypothalamic GLU and GABA concentrations. With the limitations inherent to any animal model, these data obtained from a 5-day exposure study with rats suggest, but do not unequivocally prove, that styrene may have also no reproductive toxicity effects in men chronically exposed to this chemical.     

Effects of furan on male rat reproduction parameters in a 90-day gavage study

Furan is produced in foods during processing and preservation techniques that involve heat treatment. Previously, we reported that furan-exposed rats exhibited dose-dependent gross and histological changes in liver which correlated with changes in liver serum enzymes ALT, AST and ALP. Here we report the effects of furan on the male reproductive system. There were no histological or weight changes in the reproductive organs. Serum testosterone levels were increased in a dose-dependent manner whereas serum LH was decreased. There were no changes in 17-OHase, 3β-HSD and 17β-HSD activities or serum FSH. Furan did not alter mRNA expression levels for the LH receptor or Tspo but in contrast, mRNA levels of StAR were increased in all doses of furan. The mRNA for the cholesterol side-chain cleavage enzyme (Cyp11a1) was increased by furan at the high dose, as was the level of intratesticular testosterone. We conclude that subchronic furan exposure affects testicular steroidogenesis.     

Comparative evaluation of a 5-day Hershberger assay utilizing mature male rats and a pubertal male assay for detection of flutamide's antiandrogenic activity.

A 5-day Hershberger assay utilizing mature male rats and a pubertal male assay were evaluated for the ability to detect antiandrogenic compounds such as flutamide, an androgen receptor antagonist. Six days after the operation, implantation with two silicon capsules containing testosterone (T) (30 mg/capsule) in castrated rats provided the ventral prostate and seminal vesicle weights as well as serum T and luteinizing hormone (LH) levels equivalent to those of the controls (non-castrated, non-implanted rats). Castrated rats implanted with two T-capsules (6 rats/dose) were treated by gavage for 5 days with vehicle (0.5% carboxymethylcellulose) or flutamide (0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles and the levator ani plus bulbocavernosus muscles (> or =0.6 mg/kg/day) and ventral prostate (> or =2.5 mg/kg/day), and an increase in serum LH levels (> or =2.5 mg/kg/day), but no changes in serum T levels. When age-matched intact male rats were treated with 10-mg/kg/day flutamide, a significant increase in serum T levels was observed concomitant with a tendency of increased LH. The organ weights were also decreased; however, the changes were less than those in the castrated, T-implanted rats. Immature intact male rats (10 rats/dose) were treated for 20 days with flutamide (0, 0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles at 2.5 and 10 mg/kg/day. Serum LH levels, but not T levels, were increased at 10 mg/kg/day. Statistical significance of some of these changes was not observed in the 6 animals/dose examined. Our findings support that the Hershberger assay, in the current conditions, is the most sensitive among the assays examined and a useful short-term screening method for the detection of antiandrogenic compounds.     

日本海马对雄性大鼠附性器官及垂体——性腺轴的影响

本实验研究中药小海马（日本海马）,给雄性大鼠口服20d后,测定血浆睾酮、促性腺激素FSH和LH浓度,以及观察附属性腺的组织学改变。实验证实,日本海马能明显提高去睾后幼年大鼠血浆睾酮水平,改善精囊和前裂腺的组织学改变,对垂体精子生成素（FSH）、间质细胞刺激素（LH）含量无影响。能明显提高正常大鼠血浆睾酮含量,并能增加前列腺及精囊重量。     

Variation in tolerance to the antinociceptive,hormonal and thermal effects of morphine after a 5-day pre-treatment of male rats with increasing doses of morphine

The manifestation of tolerance to the effects of morphine on nociception and the secretion of anterior pituitary hormones, and the correlation of hormonal effects to changes in body temperature and to hypothalamic monoamines were studied in male rats. Morphine (three times a day in increasing doses) or saline (control) were administered intraperitoneally during a 5-day treatment and either saline or morphine was administered as an acute challenge 92 h later. The influence of the thermal environment on the effect of morphine on the body temperature was also studied.The 5-day morphine regimen was sufficient for the development of tolerance to the antinociceptive effect of morphine. After a 92-h lag-time, the tolerance was still complete. Tolerance to the depressant effect of morphine (10–25 mg/kg) on cold-stimulated TSH secretion was seen at 2 h, but was only barely detectable at 1 h, after the injection of a challenge dose. On the other hand, a tolerance to the stimulatory effect of morphine on prolactin secretion was already seen 1 h after the acute dose of morphine. Tolerance to the hypothermic effect of morphine (25 mg/kg) was evident in rats kept at +4°C after the challenge dose. On the contrary, no tolerance to the hyperthermic effect of morphine (15 or 25 mg/kg) was observed in rats kept at +30°C. However, the hyperthermia was reversed when these rats were moved to +4°C for 30 min, irrespective of whether they were morphine pretreated or not. Thus the removal of the hyperthermic stimulus decreased the core temperature of all rats.We conclude, that with a 5-day morphine regimen and a 4-day lag time, tolerance developed to the antinociceptive, hypothermic and some hormonal effects of mor phine but not to its hyperthermic effect or to its effects on hypothalamic 5-HIAA concentrations. Neither the changes in the rectal temperature nor the minor alterations in the concentrations of the hypothalamic amine neurotransmitters correlated with the manifestation of tolerance to the cold-stimulated TSH secretion. Correspondence to: P. T. Mannisto at the above address     

Immunotoxic effects of 2-bromopropane in male Sprague-Dawley rats: a 28-day exposure study

Immunotoxic effects of 2-bromopropane were investigated in male Sprague-Dawley rats. The rats were treated orally daily with 2-bromopropane at 100, 330, or 1000 mg/kg for 28 consecutive days. Four days before necropsy, the rats were immunized intravenously with sheep red blood cells (SRBCs). The body and thymus weights were significantly reduced by treatment with 2-bromopropane at the highest dose. In addition, the numbers of splenic and thymic cells were decreased by 2-bromopropane. In hematology, the numbers of white blood cells, red blood cells, and platelets were significantly reduced. Among the serum clinical parameters, the levels of chloride ion were significantly increased by 2-bromopropane. The antibody response to SRBCs was significantly suppressed at the highest dose. With immunized animals, immunophenotyping of splenic and thymic cells was performed to investigate the changes of the number of macrophages, B cells, and T cells in spleen and the number of CD4+ and CD8+ cells in thymus. The numbers of most cell types were significantly decreased in the spleen when animals were treated with 2-bromopropane at 1,000 mg/kg. Likewise, all cell types of thymus were significantly decreased by 2-bromopropane. The present results suggest that 2-bromopropane may have an immunotoxic potential in male Sprague-Dawley rats when the rats are exposed for 28 d.     

钙对大鼠下丘脑-垂体-性腺轴功能的影响

目的 探讨钙对下丘脑-垂体-性腺轴的影响.方法 20日龄雌性SD大鼠50只随机均分为正常对照组(每日生理盐水灌胃,6d后生理盐水0.2ml皮下注射,每日2次)、性早熟模型组(每日生理盐水灌胃,6d后N甲基-DL-天冬氨酸40 mg/kg皮下注射,每日2次)和钙高、中、低剂量组(分别用碳酸钙0.5、0.25、0.125g· kg-1·d-1灌胃,6d后生理盐水0.2 ml皮下注射,每日2次).计算大鼠子宫指数、卵巢指数,实时荧光定量PCR法检测下丘脑促性腺激素释放激素(GnRH)mRNA的表达.结果 钙高剂量组子宫指数、卵巢指数及下丘脑GnRH mRNA含量与性早熟模型组相仿(P＞0.05),均高于钙中、低剂量组和正常对照组(P＜0.05);钙中、低剂量组上述指标与正常对照组相仿(P＞0.05).结论 钙与大鼠下丘脑-垂体-性腺轴密切相关,对性发育起重要调节作用.     

Acute toxic effects of 3,3′-iminodipropionitrile on hypothalamic-pituitary-gonadal axis in male rats

Exposure to 3,3′-iminodipropionitrile (IDPN) causes persistent neurotoxicity, while its reproductive toxicity in female rats is transient, indicating that gonadotropin-releasing hormone (GnRH) neurons and gonadotrophs receive little or no damage from IDPN and that the transient gonadal toxicity may be also observed in males. To clarify these points, the acute toxic effects of IDPN on hypothalamic-pituitary-gonadal axis of male rats were examined histologically, biochemically and serologically. A single intraperitoneal injection of IDPN (1000 mg/kg body weight) induced signs of neurotoxicity within a day; nevertheless, GnRH neurons were not affected throughout the experimental period. Four days after IDPN treatment, the plasma level of testosterone but not gonadotropins decreased and active caspase 3-immunopositive spermatids increased; both parameters returned to normal levels afterwards. Data from our studies revealed that while IDPN had little or no toxic effect on GnRH neurons or gonadotrophs it was transiently toxic to gonads in both sexes.     

The role of adrenal and pineal glands on the hypothalamo-pituitary axis in adult male rats

Although there have been reports on the effects of adrenal and pineal gland secretions on the hypothalamus and the pituitary, the maintenance of rhythmicity by these glands has not been reported so far. The present data deals with the alterations in the periodicity of hypothalamo-pituitary axis after the surgical removal of either adrenal, gonad or pineal in adult male rats. The data indicated an alteration in the 24 hour pattern of hypothalamic content of LHRH after adrenalectomy, castration or pinealectomy. In adrenalectomy group, the in vitro responsiveness of pituitary decreased at 0600 h and 100 h as compared to the intact rats, resulting in a low amplitude of LH circadian rhythm. The pituitaries of pinealectomized rats showed increased sensitivity at 1000 h and 1800 h which resulted in two peak LH concentration at those time intervals. Further, pinealectomized rats showed a selective five fold increase over 24 hr in serum FSH concentration as compared to intact rats suggesting dissociation in the release of FSH and LH.     

Evaluation of a 15-day screening assay using intact male rats for identifying antiandrogens.

An in vivo screening assay using intact adult male rats has been evaluated for its ability to detect six antiandrogenic compounds via oral administration. The test compounds included cyproterone acetate (CPA), flutamide (FLUT), p,p'-DDE (DDE), di-n-butyl phthalate (DBP), linuron (LIN), and vinclozolin (VCZ). Two of the test compounds (DDE and FLUT) have been previously evaluated in the 15-day intact male assay with compound administration via intraperitoneal injection (ip). For the current studies, male rats were dosed for 15 days via oral gavage and euthanized on the morning of test day 15. The endpoints evaluated included final body and organ weights (liver, thyroid gland, testes, epididymides, prostate, seminal vesicles with fluid, accessory sex gland unit [ASG]), serum hormone concentrations (testosterone [T], estradiol [E2], dihydrotestosterone [DHT], luteinizing hormone [LH], follicle stimulating hormone [FSH], prolactin [PRL], T(3), T(4), and thyroid stimulating hormone[TSH]), and histopathology of the testis, epididymis, and thyroid gland; positive results for each endpoint are described below. In addition, an evaluation of immune system endpoints (humoral immune function, spleen and thymus weights, and spleen cell number) was conducted on a subset of animals dosed with either DDE or FLUT. All six endocrine-active compounds (EACs) increased relative liver weight. FLUT and VCZ caused the typical pattern for an androgen receptor (AR) antagonist, although not all endpoints were statistically significant for VCZ: decreased ASG weights, hormonal alterations (increased T, DHT, LH, and FSH), and induced Leydig cell hypertrophy and/or hyperplasia. CPA caused effects consistent with its mixed AR antagonist/progesterone receptor agonist activity: it decreased ASG weights, caused hormonal alterations (increased T and E2; decreased FSH), and caused spermatid retention. DBP, a compound with antiandrogen-like activity via a nonreceptor mediated mechanism, caused hormonal alterations (decreased T, DHT, and E2; increased LH, FSH, and PRL) and induced general testicular degeneration. LIN, a weak AR antagonist, decreased ASG weights, caused hormonal alterations (decreased T, DHT, and LH; increased E2), and caused spermatid retention. Unlike the other AR antagonists evaluated, DDE, a weak AR antagonist, did not alter reproductive parameters. All six antiandrogens caused some effects on thyroid parameters, although only CPA, DDE, and VCZ caused results consistent with a potential thyroid-modulator. FLUT and DDE did not alter the primary humoral immune response to SRBC, spleen or thymus weights, or spleen cell number. In the current study, 5 of the six test substances were identified as endocrine-active substances consistent with their known/proposed mechanism(s) of action. The effects that were observed in the current study via oral (gavage) compound administration were similar to the responses that were observed by the ip route in previous studies for DDE and FLUT. This report, in addition to the > 20 compounds that have already been examined using the 15-day intact male assay, supports this assay as a viable screening assay for detecting EACs, and also illustrates that the ability to identify EACs using the intact male assay will be equivalent regardless of the route of compound administration.     

Biochemical effects of chloral hydrate on male rats following 7-day drinking water exposure

The biochemical and toxicological effects of chloral hydrate were investigated. Four groups (n = 7 per group) of male Sprague-Dawley rats (161-170 g) were administered chloral hydrate in drinking water at concentrations of 20, 200 or 2000 ppm for 7 days. The control group received phosphate-buffered water only. There were no treatment-related changes in the body weight gains, relative weights of major organs or haematological parameters. Trichloroacetic acid was significantly (P < 0.05) elevated in the serum of high-dose animals (7.75 +/- 5.14 mg dl(-1), mean +/- SD). In the high-dose animals there was a 36% increase in protein level in the liver homogenates but not in the corresponding 9000 g supernatants. Concurrently, there was a threefold increase in the activity of the hepatic peroxisomal enzyme palmitoyl CoA oxidase (PCO). A prominent change was the dose-related suppression in hepatic aldehyde dehydrogenase (ALDH) activity observed in all treatment groups, with the decrease ranging from 15% at 20 ppm to 68% at 2000 ppm. There were no significant decreases in the activity of hepatic enzymes ethoxyresorufin O-deethylase (EROD), benzyloxyresorufin O-dealkylase (BROD) and UDP-glucuronosyl-transferase (UDPGT). In the high-dose group there was a 30% increase in hepatic glutathione-S transferase (GST) activity, accompanied by a 13% increase in glutathione (GSH). Significant effects on lipids were observed in the liver of the high-dose animals, with a 15% decrease in hepatic cholesterol and triglyceride levels. There were no treatment-related changes in serum chemistry parameters, including cholesterol and triglyceride levels. Although in vitro assays showed chloral hydrate to be an inhibitor of serum pseudocholinesterase activity, with a 50% inhibition concentration (ic(50)( of approximately 0.7 mM at 5 mM butyrylthiocholine, no decrease in serum pseudocholinesterase activity was found in the treated animals. It was concluded that the liver is the target organ for chloral hydrate, with suppression of ALDH as the most sensitive endpoint followed by alteration in the GSH level and GST activity. Changes observed in the high-dose animals, such as increased peroxisomal PCO activity in the liver and perturbation of lipid homeostasis in the liver and blood, were likely to be associated with trichloracetic acid, the major metabolite of chloral hydrate.     

二甲双胍对大鼠垂体—性腺轴内分泌功能的影响

目的研究二甲双胍(Metformin,MF)对大鼠垂体-性腺轴内分泌功能的影响。方法采用放射免疫分析法和电子显微镜技术,系统研究MF对大鼠血清性激素含量及靶腺组织形态的影响。结果MF135mg·kg-1·d-1,ig,连续用药14d,可使♂大鼠睾酮(T)的含量及♀大鼠血清黄体生成素(LH)水平明显降低,而对♀大鼠卵泡刺激素(FSH)、雌二醇(E2)、孕酮(P)的含量和♂大鼠血清LH、FSH的含量均无影响。270mg·kg-1·d-1MF除明显降低♂大鼠血清T和♀大鼠血清LH的含量外,可使♀大鼠血清P、E2的含量升高(P<0.01)。电镜观察显示,大鼠睾丸内分泌细胞超微结构发生退行性改变,而卵巢细胞超微结构则呈现分泌旺盛的表现。结论MF对♀大鼠垂体-卵巢轴内分泌功能有促进作用,而对♂大鼠垂体-睾丸轴内分泌功能有抑制作用,且使靶腺内分泌细胞的超微结构出现相应的变化。     

Effects of estradiol treatment on voluntary and forced alcohol consumption in male rats.

Estrogens have been related to alcohol as a dependent variable, but scarcely as a causal variable, that affects the alcohol consumption. The scope of the present work was to study the effect of estrogens on both the amount and the pattern of alcohol consumption. Male Wistar rats were individually exposed to forced alcohol consumption (FAC) and voluntary alcohol consumption (VAC) in each of the following four periods: precastration (PreC), postcastration (PosC) or post-sham castration, estradiol (E) treatment (5 microg of estradiol benzoate/day/rat) and postestradiol (PosE). Estrogenic treatment reduced significantly the alcohol consumption with respect to the PreC and PosE periods in castrated (C) males during VAC. E treatment showed the lowest value of alcohol intake in FAC, but differences were significant only with respect to PreC regardless of the male gonadal condition. E treatment decreased food intake regardless of the male gonadal condition in both FAC and VAC. Castration and E treatment modified differentially the patterns of alcohol consumption depending on the volitive characteristics of alcohol intake. Castration reduced the size of the licking rates without affecting the number of drinking bouts in FAC. This pattern was maintained in the E and PosE periods of C males. Castration did not affect the pattern of alcohol consumption in VAC, but estrogen reduced both the bout size and the number of bouts during the day, which gave an additional support to the inhibitory effect of estrogens on VAC. Results are discussed in terms of a possible inhibitory action of estrogens on the opioid system, which possibly reduces the rewarding properties of alcohol.     

Effects of heat-stress on behavior and the pituitary adrenal axis in rats

Three experiments were performed in order to analyse the behavioral and biochemical correlates of four different intensities of the same stressor. In experiment 1, rats were exposed to heat stress (hot-plate) of varying temperatures for 30 seconds. Activity was recorded in an open field immediately after stress for 30 minutes. The data revealed that the milder temperatures increased (21, 47, 52°C), while the higher temperature (57°C) decreased activity. Experiment 2 assessed the pituitary-adrenal response to the different temperatures by measuring levels of plasma corticosterone 30 minutes after stress. The four levels of hot-plate temperatures induced differential levels of corticosterone which may best be described as an inverted U-shaped function, with only the extreme temperature (57°) inducing a significant elevation in levels of the steroid. Experiment 3 further manipulated the pituitary adrenal axis by administering dexamethasone 25 hr and 1 hr before stress and ACTH 15 min before stress. Both affected activity levels by depressing locomotion regardless of the stress intensity. These results are compared to other studies that have addressed the question of stress-induced activation and it is suggested that stress is not a unitary concept, but interacts with the performance of certain behaviors to produce both facilatory or inhibitory results.