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Endocrine disrupting chemicals bind to a novel receptor, microtubule‐associated protein 2, and positively and negatively regulate dendritic outgrowth in hippocampal neurons
Author(s) -
Matsunaga Hayato,
Mizota Kaori,
Uchida Hitoshi,
Uchida Takafumi,
Ueda Hiroshi
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06847.x
Subject(s) - pregnenolone , hippocampal formation , chemistry , neurite , agonistic behaviour , medicine , endocrinology , microbiology and biotechnology , biology , hormone , biochemistry , steroid , in vitro , psychology , psychiatry , aggression
J. Neurochem. (2010) 114 , 1333–1343. Abstract The present study demonstrates a novel high‐affinity neuronal target for endocrine disrupting chemicals (EDCs), which potentially cause psychological disorders. EDCs competitively inhibited the binding of bovine serum albumin‐conjugated progesterone to recombinant human microtubule‐associated protein 2C (rhMAP2C) with an inhibition constant at picomolar levels. In the rhMAP2C‐stimulated tubulin assembly assay, agonistic enhancement was observed with dibutyl phthalate and pentachlorphenol and pregnenolone, while an inverse agonistic effect was observed with 4‐nonylphenol. In contrast, progesterone and many of the EDCs, including bisphenol A, antagonized the pregnenolone‐induced enhancement of rhMAP2C‐stimulated tubulin assembly. These agonistic and inverse agonistic actions were not observed in tubulin assembly stimulated with Δ1–71 rhMAP2C, which lacks the steroid‐binding site. Using a dark‐field microscopy, pregnenolone and pentachlorphenol were observed to generate characteristic filamentous microtubules in a progesterone‐ or bisphenol A‐reversible manner. In cultured hippocampal neurons, similar agonist‐antagonist relationships were reproduced in terms of dendritic outgrowth. Fluorescent recovery after photobleaching of hippocampal neurons showed that pregnenolone and agonistic EDCs enhanced, but that 4‐nonylphenol inhibited the MAP2‐mediated neurite outgrowth in a progesterone‐ or antagonistic EDC‐reversible manner. Furthermore, none of the examined effects were affected by mifepristone or ICI‐182,786 i.e. the classical progesterone and estrogen receptor antagonists. Taken together, these results suggest that EDCs cause a wide variety of significant disturbances to dendritic outgrowth in hippocampal neurons, which may lead to psychological disorders following chronic exposure during early neuronal development.