The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.
Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Eduardo
E
Merlo
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Priscila L
PL
Podratz
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Gabriela C
GC
Sena
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Julia F P
JF
de Araújo
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Leandro C F
LC
Lima
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Izabela S S
IS
Alves
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Letícia N
LN
Gama-de-Souza
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Renan
R
Pelição
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Lívia C M
LC
Rodrigues
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Poliane A A
PA
Brandão
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Maria T W D
MT
Carneiro
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Rita G W
RG
Pires
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Cristina
C
Martins-Silva
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Tamara A
TA
Alarcon
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Leandro
L
Miranda-Alves
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Ian V
IV
Silva
Department of Morphology (E.M., P.L.P., G.C.S., J.F.P.d.A., I.S.S.A., L.N.G.-d.S., I.V.S., J.B.G.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Biophysics and Physiology (L.C.F.L.), Federal University of Minas Gerais, Vitória ES, 29040090 Brazil; Department of Physiological Sciences (R.P., L.C.M.R., R.G.W.P., C.M.-S., T.A.A.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Department of Chemistry (P.A.A.B., M.T.W.D.C.), Federal University of Espírito Santo, Vitória ES, 29040090 Brazil; Experimental Endocrinology Research Group (L.M.-A.), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil; and Postgraduate Program in Endocrinology (L.M.-A.), School of Medicine, Federal University of Rio de Janeiro, Vitória ES, 29040090 Brazil.
Jones B
JB
Graceli
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D052244:Endocrine Disruptors / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D014220:Trialkyltin Compounds; C011559:tributyltin