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.     

Cadmium exposure differentially modifies the circadian patterns of norepinephrine at the median eminence and plasma LH, FSH and testosterone levels

This work was designed to analyze the cadmium effects on time-of-day variations of norepinephrine (NE) content in median eminence and on plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone in adult male rats. Rats were given cadmium at a dose of 25 ppm of cadmium chloride (CdCl(2)) in the drinking water for 1 month. Significant 24-h changes of NE content in the median eminence, plasma LH and testosterone levels occurred in control animals. Cadmium exposure induced a phase advance of the nocturnal peak of NE content that was described in the control group, to 12h and increased its amplitude. However, the mean NE content was not changed by cadmium. Metal exposure abolished the daily pattern of plasma LH levels, although the mean levels of the hormone were not modified by cadmium. For testosterone, the metal increased the amplitude of its nocturnal peak and induced the appearance of another peak during the light phase at 12h, thus increasing the mean plasma levels of this hormone. An interaction between the metal and time for NE and plasma testosterone levels was observed. These data suggest that cadmium exerts differential effects at the median eminence, the pituitary and the testes, that may explain the changes in the 24-h pattern of plasma testosterone levels.     

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 morphine, beta-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat

Intraperitoneal administration of the opiate antagonist naloxone hydrochloride (30 mg/kg) to sexually experienced male rats caused a significant reduction in mount and intromission latencies, number of mounts preceding ejaculation and ejaculation latencies. Intraperitoneal adminstration of naloxone (30 mg/kg) also stimulated persistant non-copulators to begin mating and to ejaculate within a twenty minute test period. Conversely, intraperitoneal administration of morphine sulphate (6 mg/kg) as well as intraventricular injection of the endogenous opiate beta-endorphin (6 micrograms) produced a complete loss of copulatory behavior in male rats. The deficit in sexual behavior induced by beta-endorphin was correlated with a significant increase in hypothalamic norepinephrine levels. It is suggested that the endogenous opiates may be involved in the mediation of sexual behavior via an interaction with central catecholaminergic systems.     

Paint thinner exposure inhibits testosterone synthesis and secretion in a reversible manner in the rat

Occupational exposure and sniffing of toluene-based organic solvents is an important public health problem. In this study, we have investigated the effects of paint thinner inhalation on testosterone synthesis and secretion in the male rat. A control group inhaled normal air ventilation. The remaining animals were divided into three groups and exposed to paint thinner in a glassy cage for 15 and 30 days (2 h/day). A group of rats was allowed to recover for 15 days after 30 days of exposure. Toluene concentration (the largest constituent in thinner, 66%) was set at 1500 ppm in the inhaled air. At the end, all animals were decapitated and blood samples obtained. Testes and seminal vesicles were removed and weighed out. Serum total testosterone levels were determined by chemiluminescence enzyme immunoassay. Testicular tissue specimens were processed for semi-quantitative evaluation of immunohistochemical testosterone staining and light microscopy. Intensity of immunostaining was evaluated on a scale between 0 (no staining), 1 (minimal), 2 (mild), 3 (moderate) and 4 (strong staining). Serum testosterone levels (ng/ml) were decreased by 15-day (3.31 ± 0.61) and 30-day (1.17 ± 0.54, p < 0.02) thinner exposure compared to the controls (3.91 ± 1.03). Another group of rats exposed to thinner for 30 days and then allowed to recover for a period of 15 days had significantly elevated levels of testosterone values (3.77 ± 1.1; p < 0.05). Immunohistochemical testosterone staining of the cytoplasm of Leydig cells was moderate (3+) and mild (2+) in 15 and 30 days thinner inhalation groups, respectively. Strong staining (4+) was restored following the recovery period. Testicular weight was significantly reduced in all test groups compared to the control values (p < 0.01). Diameters of seminiferous tubules were significantly decreased in the solvent exposed groups with enlarged connective tissue. The present findings suggest that paint thinner inhalation inhibits testosterone synthesis and secretion by a direct action on the Leydig cells in a reversible manner.     

Paint thinner exposure inhibits testosterone synthesis and secretion in a reversible manner in the rat

Occupational exposure and sniffing of toluene-based organic solvents is an important public health problem. In this study, we have investigated the effects of paint thinner inhalation on testosterone synthesis and secretion in the male rat. A control group inhaled normal air ventilation. The remaining animals were divided into three groups and exposed to paint thinner in a glassy cage for 15 and 30 days (2 h/day). A group of rats was allowed to recover for 15 days after 30 days of exposure. Toluene concentration (the largest constituent in thinner, 66%) was set at 1500 ppm in the inhaled air. At the end, all animals were decapitated and blood samples obtained. Testes and seminal vesicles were removed and weighed out. Serum total testosterone levels were determined by chemiluminescence enzyme immunoassay. Testicular tissue specimens were processed for semi-quantitative evaluation of immunohistochemical testosterone staining and light microscopy. Intensity of immunostaining was evaluated on a scale between 0 (no staining), 1 (minimal), 2 (mild), 3 (moderate) and 4 (strong staining). Serum testosterone levels (ng/ml) were decreased by 15-day (3.31 ± 0.61) and 30-day (1.17 ± 0.54, p < 0.02) thinner exposure compared to the controls (3.91 ± 1.03). Another group of rats exposed to thinner for 30 days and then allowed to recover for a period of 15 days had significantly elevated levels of testosterone values (3.77 ± 1.1; p < 0.05). Immunohistochemical testosterone staining of the cytoplasm of Leydig cells was moderate (3+) and mild (2+) in 15 and 30 days thinner inhalation groups, respectively. Strong staining (4+) was restored following the recovery period. Testicular weight was significantly reduced in all test groups compared to the control values (p < 0.01). Diameters of seminiferous tubules were significantly decreased in the solvent exposed groups with enlarged connective tissue. The present findings suggest that paint thinner inhalation inhibits testosterone synthesis and secretion by a direct action on the Leydig cells in a reversible manner.     

Iprodione delays male rat pubertal development, reduces serum testosterone levels, and decreases ex vivo testicular testosterone production

Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to procymidone and vinclozolin. All three of these fungicides induce Leydig cell tumors in the rat testis in long-term studies and an endocrine mode of action has been hypothesized to mediate this effect. Although both procymidone and vinclozolin antagonize the androgen receptor (AR) in vitro and in vivo, IPRO does not appear to be an AR antagonist. We proposed that pubertal exposure to IPRO would delay male rat pubertal development and reduce testosterone production within the testis. Sprague-Dawley weanling rats were dosed by gavage with 0, 50, 100, or 200mg/kg/day of IPRO from post-natal day (PND) 23 to 51/52. The onset of puberty (progression of preputial separation (PPS)) was measured starting on PND 37. Organ weights, serum hormones, and ex vivo testis steroid hormone production under stimulated (+human chorionic gonadotropin (hCG)) and unstimulated (-hCG) conditions were measured at necropsy. IPRO delayed PPS at 100 and 200mg/kg/day and decreased androgen sensitive seminal vesicle and epididymides weights at 200mg/kg/day. Furthermore, IPRO increased adrenal and liver weights at 200mg/kg/day, presumably by different mechanism(s) of action. Serum testosterone levels were decreased along with serum 17alpha-hydroxyprogesterone and androstenedione whereas serum LH was unaffected. IPRO reduced ex vivo testis production of testosterone and progesterone. Taken together, these results suggest that IPRO affects steroidogenesis within the testis, not through disruption of LH signaling, but possibly through enzyme inhibition of the steroidogenic pathway before CYP17. These data, along with the reported failure of IPRO to elicit an AR antagonism in vitro, provide evidence that IPRO differs from the dicarboximides procymidone and vinclozolin in that the effects on male rat pubertal development result from an inhibition of steroidogenesis and not AR antagonism.     

Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat

Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.     

Effects of TRH and a rat TSH preparation on discrete hypothalamic and forebrain catecholamine nerve terminal networks in the hypophysectomized male rat

A rat pituitary TSH preparation in doses of 10 and 100 micrograms/kg produced rapid and marked increases in dopamine (DA) levels and alpha-methyltyrosine-induced decline consistent with increased DA synthesis and release in the medial and lateral palisade zones (MPZ, LPZ) of the median eminence, and reduced noradrenaline (NA) turnover in the paraventricular hypothalamic nucleus (PA) of the hypophysectomized male rat. The TSH serum levels measured in these rats 2 h after the injection were within the physiological range after the injection of 10 micrograms/kg. TRH given intravenously in a dose of 100 micrograms/kg produced rapid and marked increases of DA release in the MPZ and LPZ of the median eminence and reduction of NA turnover in the PA of the hypophysectomized male rat. The TRH injection did not alter the serum levels of prolactin, TSH, T3 and T4. The results indicate that TRH-TSH-DA interactions take place in the local circuits in the median eminence thus supporting the view that a short and an ultrashort feedback action of rTSH and TRH respectively may exist in the median eminence. The rapid action of the rat TSH preparation as well as of TRH further supports this concept. The rat TSH preparation and TRH produced marked reductions in NA turnover in the PA. These results support the possibility that rat TSH and TRH may, via an action on the hypothalamus, influence the facilitatory noradrenergic mechanism operating at the soma-dendritic level of the TRH immunoreactive neurons projecting to the median eminence. Thus, the existence of a neuronal feedback loop from the medio-basal hypothalamus into the paraventricular hypothalamic nucleus is postulated.     

Effects of tioconazole on parturition and serum levels of 17 beta-oestradiol, progesterone, LH and PRL in the rat

Tioconazole, an imidazole antifungal agent, was administered orally at 100 mg/kg/day to pregnant rats according to two regimens; in one, treatment started on day 15 post-insemination (p.i.) and in the other it started on day 18 p.i. The first regimen caused a delay in onset of parturition and a prolongation of labour. Serum progesterone was decreased from days 17 to 21 p.i., 17 beta-oestradiol decreased on day 21 p.i., LH increased on day 17 p.i., and the normal surge of prolactin on day 21 p.i. abolished. The parturition disorders disappeared when 17 beta-oestradiol (0.125 microgram/animal/day s.c.) was given with tioconazole from day 15 p.i. In the second regimen, tioconazole treatment advanced by about 24 hours the onset of parturition and the normal fall in serum progesterone and the surge in prolactin. Serum 17 beta-oestradiol was unaffected, but LH was raised on days 19 and 20 p.i. In animals receiving progesterone (2.5 mg/animal/day, s.c.) and tioconazole from day 18 p.i. parturition was no longer advanced. In conclusion, the parturition disorders observed in rats during tioconazole treatment are associated with a modification of progesterone and 17 beta-oestradiol serum levels. These findings have questionable relevance for the human situation as the roles of these steroid hormones in parturition in women are different from those in rats.     

Effects of withdrawal from chronic exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat

Summary A 48 h but not a 72 h or 7 day withdrawal from chronic exposure to cigarette smoke was associated with increased noradrenaline levels (quantitative histofluorimetry) in the subependymal layer (SEL) of the median eminence, the anterior periventricular hypothalamic region (PV I) and the parvocellular part of the hypothalamic nucleus (PA FP) and an increased noradrenaline utilization (tyrosine hydroxylase inhibition by MT) in the SEL and the PV I. Following a 48 h or 72 h but not a 7 day withdrawal from chronic exposure to cigarette smoke an increased catecholamine utilization was found in the medial palisade zone (MPZ) of the median eminence. Reduced serum prolactin, FSH and corticosterone levels were found following a 48 h withdrawal from chronic exposure to cigarette smoke. Following a 72 h withdrawal from chronic exposure to cigarette smoke a reduced concentration of serum prolactin was noted. Chronic exposure to cigarette smoke reduced serum TSH levels and lead to a tolerance development with regard to noradrenaline levels and utilization within the preoptic region with the exception of the periventricular preoptic region. The finding of special interest in the present study is the demonstration of a highly significant lowering of corticosterone serum levels despite maintained blood levels of ACTH as seen 48 h following withdrawal. It is suggested that this type of endocrine change may lead to changes in fear-motivated behaviour and contribute to behavioural withdrawal reactions. The maintained reductions of serum prolactin levels found after 48 h and 72 h of withdrawal from cigarette smoke exposure (cf. Andersson et al. 1985a) is discussed in terms of an increased catecholamine utilization in the medial palisade zone of the median eminance. This activation is suggested to be caused by the development of a prolactin receptor supersensitivity within the medium eminence. The present evidence indicates withdrawal effects mainly in the noradrenaline nerve terminals of the sub-ependymal layer of the median eminence, the anterior periventricular hypothalamic region and the parvocellular part of the paraventricular hypothalamic nucleus which inter alia are involved in regulation of ACTH secretion (cf. Andersson et al. 1985a).     

Effects of acute continuous exposure of the rat to cigarette smoke on amine levels and utilization in discrete hypothalamic catecholamine nerve terminal systems and on neuroendocrine function

Summary The effects of acute continuous exposure to the smoke from 1–4 cigarettes have been studied in the male rat in terms of hypothalamic catecholamine levels and utilization as well as the secretion of anterior pituitary hormones. Catecholamine levels in discrete hypothalamic catecholamine nerve terminal systems were studied by quantitative histofluorimetry. Catecholamine utilization was studied by means of the tyrosine hydroxylase inhibition method using -methyl-(±)-p-tyrosine methyl ester. The serum hormone levels of adenohypophyseal hormones and of corticosterone were measured by the use of radioimmunoassay procedures. The results show that acute continuous exposure to unfiltered but not to filtered (Cambridge glass fibre filters) cigarette smoke leads to small but dose-dependent reductions of amine levels in most of the hypothalamic noradrenaline and dopamine nerve terminal system. These effects were associated with an enhancement of regional hypothalamic noradrenaline utilization but not of dopamine utilization in the median eminence. Furthermore, a reduction of TSH and prolactin serum levels was noted as well as increases in ACTH secretion. These results are partly different from those previously obtained with rats acutely exposed to intermittent unfiltered cigarrete smoke. This difference is suggested to be due to a temporary blockade of catecholamine release following acute continuous exposure to cigarette smoke.This work has been supported by a grant (1223) from the Council for Tobacco Research, New York, USA and by a grant from the Svenska Tobaks monopolet Send offprint requests to K. Andersson at the above address     

Effects of low-level lead exposure on hypothalamic hormones and serum progesterone levels in pregnant guinea pigs.

Pregnant guinea pigs were given a daily oral dose of 0, 5.5, or 11 mg lead (as lead acetate) per kg body weight during days 22-52 or 22-62 of gestation. Maternal serum progesterone levels were measured at the end of treatment, as well as hypothalamic levels of gonadotropin-releasing hormone (GnRH) and somatostatin (SRIF) in both the mothers and fetuses. Lead-treated dams had lower serum concentrations of progesterone at the end of treatment than did vehicle-treated animals. This effect was statistically significant for the higher Pb dose only. Hypothalamic levels of GnRH and SRIF were reduced in a dose-dependent manner by lead treatment in both dams and fetuses. The reduction of SRIF levels in 52-day-old fetuses was particularly severe (92%) in the 11 mg group. However, neither litter size nor body and organ weights, including placental weight, of the dams and fetuses was significantly affected. The relevance of these hormonal decreases is unknown, but could include decreased reproductive capacity in both the dams and fetuses that does not become apparent until later in the life-cycle.     

Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat.

The effects of pinealectomy and exogenous melatonin (N-acetyl-5-methoxytryptamine) on serum leptin levels were investigated in rats. Exogenous administration of melatonin to intact rats resulted in significant decreases in serum leptin levels (P < 0.05) compared to those of the intact control group. Serum leptin levels were significantly elevated in the pinealectomised rats in comparison to the sham-pinealectomised animals (P < 0.001) and were significantly suppressed by exogenous administration of melatonin compared to those of non-treated pinealectomised rats (P < 0.001). Hormone concentrations in the melatonin-treated pinealectomised group were found to be similar to those seen in the sham-pinealectomised group. These results suggest that pineal gland has an effect on leptin release.     

复方中药对多囊卵巢综合征模型大鼠血清性激素、瘦素水平的影响

目的:观察多囊卵巢综合征(PCOS)模型大鼠血清性激素T、FSH、LH及瘦素(Leptin)水平的变化,探讨复方中药对PCOS模型大鼠生殖内分泌系统的影响。方法:本实验采用Poresky法进行造模,并分别以中药、西药(罗格列酮)、中西药联合用药治疗,观察治疗后大鼠体重、血清性激素及Leptin水平的变化,并进行Leptin水平与FSH、LH、LH/FSH、T、WEIGHT的相关分析。结果:复方中药能降低血清T、LH、Leptin水平及LH/FSH比值,且血清Leptin水平与LH、T呈正相关。结论:复方中药能改善PCOS模型大鼠的生殖内分泌功能,降低血清Leptin水平。     

The effect of neuroleptic drugs on serum testosterone level in the male rat

The effects of systemically administered haloperidol (haldol) and N-ethoxycarbonyl-2-ethoxy-1,2, dihydroquinoline (EEDQ) on serum testosterone level were studied in Sprague-Dawley adult male rats. Animals were injected intraperitoneally with either 0.1, 5 and 10 mg/kg of haldol or 0.5 and 5 mg/kg of EEDQ. Animals were sacrificed at 15, 60 min, 12, 24 or 48 hr after drug treatment and blood was collected for subsequent testosterone analysis. Results obtained indicate that 10 mg/kg of haldol significantly (P less than 0.01) suppressed serum testosterone levels both at 1 and 24 hr post drug treatment. EEDQ treatment significantly (P less than 0.01) suppressed serum testosterone levels only when administered at the higher dose of 5 mg/kg. This effect was observed as long as 12 hr after drug treatment. These results suggest that high doses of haldol and EEDQ can suppress serum testosterone levels in the male rat. The sexual dysfunction associated with neuroleptic drugs may be partially due to the effects of the drugs on serum testosterone levels.     

Acute effects of nalmefene on LH, prolactin, and testosterone in male rhesus monkeys

The effects of the long-acting opioid antagonist, nalmefene [17-N-cyclopropylmethyl-3,14-beta-dihydroxy-4, 5-alpha-epoxy-6-methylene morphinan hydrochloride] on LH, T, and prolactin release in rhesus monkeys are unknown. The acute effects of nalmefene (0.01 and 0.10 mg/kg, IV) or placebo on LH, PRL, and T were studied, and samples were collected at 10-min intervals for 360 min to permit cluster analysis of pulsatile release patterns. LH increased significantly within 30 min after nalmefene, and remained significantly above baseline levels for 50 to 60 min (p < 0.05). Testosterone increased significantly within 70 to 80 min after nalmefene, and remained significantly above baseline for 60 min (p < 0.05). Although nalmefene antagonizes opioid agonists for 6-8 h, inhibitory feedback by testosterone appeared to limit the duration of its antagonism of endogenous opioid inhibition of LHRH and stimulation of LH. Nalmefene did not change LH or PRL pulse frequency or amplitude significantly in comparison to placebo administration.     

Effects of solvent exposure on testosterone levels and butyrylcholinesterase activity in mice

In female and male mice the effect of exposure to trichloroethylene (TCE) seen at the lowest concentration is an increase in liver weight. The activity of plasma butyrylcholinesterase (BuChE) increases even more than the liver weight at corresponding concentrations, but only in the males. Depletion of testosterone through castration or destruction of the pituitary gland or hypothalamus, are the only other ways to experimentally induce corresponding increases in BuChE. Plasma BuChE activity increase was found to be a common reaction after exposure to TCE, perchloroethylene, chloroform, methylene chloride and carbon tetrachloride and also after exposure to ethanol. Other solvents such as toluene, xylene, benzene and 1,1,1-trichloroethane had little or no effect on BuChE activity. Normal and castrated male mice were continuously exposed for one month to 150 p.p.m. TCE. The increase in BuChE activity after the exposure was of the same magnitude as the increase seen after castration. BuChE activity in castrated males was not further increased by TCE exposure. Administration of testosterone with osmotic minipumps for 13 days almost restored the normal testosterone and BuChE levels in castrates. The effect of TCE exposure on BuChE activity in these animals was the same as on normal males. Testosterone levels were not influenced by the TCE exposure in normal males or in castrates given testosterone. No sex hormone binding globulins (SHBG) could be detected in the mice. BuChE activity changes induced through solvent exposure are therefore neither directly nor indirectly (through SHBG) due to effects on testosterone. The results from these animal experiments do not support the epidemiological findings of decreased testosterone levels in humans exposed to solvents.     

Effects of acute intermittent exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on neuroendocrine function in the diestrous rat

Summary Diestrous female rats were exposed to the smoke from one to four cigarettes. Exposure to unfiltered cigarette smoke produced dose- and time-dependent reductions of catecholamine levels and dose- and time-dependent increase in catecholamine utilization in the various hypothalamic and preoptic dopamine and noradrenaline nerve terminal systems. These effects were counteracted by pretreatment with the ganglion blocking agent mecamylamine (1 mg/kg). Exposure to cigarette smoke was also found to produce a dose- and time-dependent inhibition of serum prolactin, LH and FSH levels which was counteracted by pretreatment with mecamylamine. Exposure to the smoke from one cigarette (but not from four cigarettes) increased serum TSH levels. In combination with tyrosine hydroxylase inhibition the exposure to cigarette smoke produced a dose- and time-dependent inhibition of plasma ACTH levels, an action which was counteracted by pretreatment with mecamylamine. The results demonstrated a sex difference (cf. Andersson et al. 1985c), in the nicotine-induced changes of TSH and ACTH secretion despite a general increase in hypothalamic and preoptic dopamine and noradrenaline utilization in both the male and the diestrous female rat. The differences in the neuroendocrine actions of acute intermittent exposure to cigarette smoke in the diestrous rat and the normal male rat are discussed. Send offprint requests to K. Andersson     

Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin.

Changes in sexual function and hormone levels are commonly found in subjects addicted to narcotics. In this study we examined 16 male and 3 female addicts who had been taking heroin (H) in the last year in doses higher than 150 mg/day. In these patients, who presented similar clinical problems, we assayed by RIA the plasma levels of heroin, testosterone, (T), dihydrotestosterone (DHT), androstenedione (A), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for periods of 150 min, 6 h and 9 h. We found a significant reduction of T and DHT concomitant with higher plasma concentrations of heroin but no relevant changes of A, LH and FSH. T and DHT returned to the initial levels after the decrease of heroin concentration. The GnRH test effectd on a female subject allowed us to make the diagnosis of hypothalamic amenorrhea. In the same patient no circadian rhythms for T, DHT and A were detected.