ABSTRACT
Perfluorooctane sulfonate (PFOS) is an endocrine disruptor highly persistent, bioaccumulative and neurotoxic, whose presence has been detected in different compartments of the environment. The aim of this study was to investigate whether PFOS could alter the HPA axis activity by modifying the gene and protein expression of corticotropin-releasing factor 1 receptor (CRF1r) and glucocorticoid receptor (Gr). For that purpose, Sprague-Dawley adult male rats were orally treated by gavage with 0.5; 1.0; 3.0 and 6.0â¯mg of PFOS/kg/day for 28 consecutive days. After PFOS administration, gene and protein expression of CRF1r were analysed in the hypothalamus, hippocampus, pituitary and adrenal glands. Moreover, Gr gene and protein expression were measured in hypothalamus, pituitary gland, prefrontal cortex, amygdala and hippocampus. The reported results indicate that (1) PFOS could inhibit HPA axis activity by diminishing gene and protein expression of CRF1r in the pituitary gland; (2) PFOS inhibits Gr protein expression in both prefrontal cortex and amygdala, which could be related to the toxic effects of this contaminant in this neuroendocrine axis and finally, (3) PFOS-treated rats would try to maintain the physiological levels of corticosterone by reducing the protein expression of Gr in the pituitary gland.
Subject(s)
Alkanesulfonic Acids/toxicity , Endocrine Disruptors/toxicity , Fluorocarbons/toxicity , Hypothalamo-Hypophyseal System/drug effects , Pituitary-Adrenal System/drug effects , Receptors, Corticotropin-Releasing Hormone/drug effects , Receptors, Glucocorticoid/drug effects , Adrenocorticotropic Hormone/blood , Animals , Corticosterone/blood , Corticotropin-Releasing Hormone/blood , Dose-Response Relationship, Drug , Down-Regulation , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Male , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/physiopathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Receptors, Corticotropin-Releasing Hormone/genetics , Receptors, Corticotropin-Releasing Hormone/metabolism , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Signal Transduction/drug effects , Time FactorsABSTRACT
This study was undertaken to evaluate the possible role of several reproductive hormone receptors on the disruption of the hypothalamic-pituitary-testis (HPT) axis activity induced by perfluorooctane sulfonate (PFOS). The studied receptors are the gonadotropin-releasing hormone receptor (GnRHr), luteinizing hormone receptor (LHr), follicle-stimulating hormone receptor (FSHr), and the androgen receptor (Ar). Adult male rats were orally treated with 1.0; 3.0 and 6.0 mg of PFOS kg(-1) d(-1) for 28 days. In general terms, PFOS can modify the relative gene and protein expressions of these receptors in several tissues of the reproductive axis. At the testicular level, apart from the expected inhibition of both gene and protein expressions of FSHr and Ar, PFOS also stimulates the GnRHr protein and the LHr gene expression. The receptors of the main hormones involved in the HPT axis may have an important role in the disruption exerted by PFOS on this axis.
Subject(s)
Alkanesulfonic Acids/pharmacology , Fluorocarbons/pharmacology , Gene Expression Regulation/drug effects , Receptors, Androgen/metabolism , Receptors, FSH/metabolism , Receptors, LHRH/metabolism , Receptors, LH/metabolism , Alkanesulfonic Acids/chemistry , Animals , Blotting, Western , Fluorocarbons/chemistry , Follicle Stimulating Hormone/metabolism , Gonadotropin-Releasing Hormone/metabolism , Luteinizing Hormone/metabolism , Male , Polymerase Chain Reaction , Rats , Rats, Sprague-Dawley , Receptors, Androgen/genetics , Receptors, FSH/genetics , Receptors, LH/genetics , Receptors, LHRH/genetics , Reproduction/drug effects , Testis/drug effects , Testis/metabolismABSTRACT
Perfluorooctane sulfonate (PFOS) is the most representative of a rising class of persistent organic pollutants perfluorochemicals. In the present study, its neurotoxicity was examined using adult male rats orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. At the end of the treatment, the dopamine concentration and its metabolism expressed like the ratio 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/dopamine were measured in the amygdala, prefrontal cortex and hippocampus. Gene and protein expression of the dopamine receptors D1 and D2 were also determined in these limbic areas. The obtained results suggest that: (1) PFOS can alter the dopamine system by modifying its neuronal activity and/or its D1 and D2 receptors in the studied brain regions; (2) the dopamine concentration and metabolism seem to be more sensitive against PFOS toxicity in the hippocampus than in the other analyzed brain areas; (3) the inhibited gene and protein expression of the D1 receptors induced by PFOS in the amygdala could be related to several changes in the HPA axis activity, and lastly; (4) the observed alterations on the dopamine system induced by PFOS could be a possible neurotoxicity mechanism of PFOS, leading to many neurological diseases.
Subject(s)
Alkanesulfonic Acids/toxicity , Amygdala/drug effects , Fluorocarbons/toxicity , Hippocampus/drug effects , Prefrontal Cortex/drug effects , 3,4-Dihydroxyphenylacetic Acid/metabolism , Amygdala/metabolism , Animals , Dose-Response Relationship, Drug , Hippocampus/metabolism , Homovanillic Acid/metabolism , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Male , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolismABSTRACT
Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release.
Subject(s)
Alkanesulfonic Acids/toxicity , Endocrine Disruptors/toxicity , Environmental Pollutants/toxicity , Fluorocarbons/toxicity , Hypothalamus, Anterior/drug effects , Hypothalamus, Middle/drug effects , Pituitary Gland, Anterior/drug effects , Prolactin/antagonists & inhibitors , Alkanesulfonic Acids/administration & dosage , Animals , Dopamine/chemistry , Dopamine/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Dose-Response Relationship, Drug , Endocrine Disruptors/administration & dosage , Environmental Pollutants/administration & dosage , Estradiol/blood , Estradiol/metabolism , Fluorocarbons/administration & dosage , GABAergic Neurons/drug effects , GABAergic Neurons/metabolism , Hypothalamus, Anterior/metabolism , Hypothalamus, Middle/metabolism , Male , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/metabolism , Pituitary Gland, Anterior/metabolism , Prolactin/blood , Prolactin/metabolism , Random Allocation , Rats, Sprague-Dawley , Supraoptic Nucleus/drug effects , Supraoptic Nucleus/metabolism , Toxicity Tests, Subacute , gamma-Aminobutyric Acid/chemistry , gamma-Aminobutyric Acid/metabolismABSTRACT
Perfluorooctane sulfonate (PFOS) is an endocrine disruptor, whose exposure can induce several alterations on the reproductive axis activity in males during adulthood. This study was undertaken to evaluate the possible role of serotonin and neuropeptide Y (NPY) on the disruption of the hypothalamic-pituitary-testicular (HPT) axis induced by PFOS in adult male rats. For that, adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0mg of PFOS/kg/day for 28 days. After PFOS exposure, serotonin concentration increased in the anterior and mediobasal hypothalamus as well as in the median eminence. The metabolism of this amine (expressed as the ratio 5-hydroxyindolacetic acid (5-HIAA)/serotonin) was diminished except in the anterior hypothalamus, with the doses of 3.0 and 6.0mg/kg/day, being this dose 0.5mg/kg/day in the median eminence. In general terms, PFOS-treated rats presented a decrease of the hypothalamic concentration of the gonadotropin releasing hormone (GnRH) and NPY. A diminution of the serum levels of the luteinizing hormone (LH), testosterone and estradiol were also shown. These results suggest that both serotonin and NPY could be involved in the inhibition induced by PFOS on the reproductive axis activity in adult male rats.
Subject(s)
Alkanesulfonic Acids/toxicity , Endocrine Disruptors/toxicity , Fluorocarbons/toxicity , Neuropeptide Y , Reproduction/drug effects , Serotonin , Animals , Gonadal Steroid Hormones/metabolism , Hypothalamo-Hypophyseal System/drug effects , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Median Eminence/drug effects , Median Eminence/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Testis/drug effectsABSTRACT
Perfluorooctane sulfonate (PFOS) is a neurotoxic agent and it can disrupt the endocrine system activity. This work was undertaken to evaluate the possible effects of PFOS exposure on the hypothalamic-pituitary-testicular axis (HPT) in adult male rats, and to evaluate the possible morphological alterations induced by PFOS in the endocrine tissues of this axis. Adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, hypothalamic noradrenaline concentration increased in the anterior hypothalamus and in the median eminence, not changing in the mediobasal hypothalamus. PFOS treated rats presented a decrease of the gonadotropin releasing hormone (GnRH) gene expression, increasing the mRNA levels of the luteinizing hormone (LH) in rats treated with all doses administered except with the dose of 6 mg/kg/day. PFOS also induced a raise of the follicle stimulating hormone (FSH) gene expression in the animals exposed to 0.5 and 1.0 mg of PFOS/kg/day. After PFOS exposure, hypothalamic GnRH concentration was modified, LH and testosterone release was inhibited and FSH secretion was stimulated. Moreover, PFOS induced several histopathological alterations in the hypothalamus, pituitary gland and testis. The results obtained in the present study suggest in general terms that PFOS can inhibit the physiological activity of the reproductive axis in adult male rats, which could be explained, at least in part, by the structural alterations showed in the animals exposed to this chemical: very dense chromatin, condensed ribosomes and a loss of the morphology in the hypothalamus; a degeneration of the gonadotrophic cells, as well as a loss and degeneration of the spermatozoids and a very marked edema in the testis.
