Environmental toxicant effects on neuroendocrine function

被引:70
作者
Gore, AC
机构
[1] Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Schwartz Dept Geriatr & Adult Dev, New York, NY 10029 USA
关键词
gonadotropin-releasing hormone; puberty; reproduction; chlorpyrifos; methoxychlor; PCB;
D O I
10.1385/ENDO:14:2:235
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Exposure to environmental toxicants can have profound effects on normal growth and development. However, the mechanisms by which these toxicants exert these effects are not well understood. Many environmental toxicants alter reproductive function and have effects on the central nervous system and behavior, yet the link between these reproductive and neurologic phenomena has not been systematically investigated. The neuroendocrine (hypothalamic-pituitary-gonadal) axis, which integrates inputs to and outputs from the nervous and reproductive systems, is functionally and anatomically situated to mediate effects of environmental toxicants, particularly those that are endocrine-disrupting chemicals (EDCs), on developmental processes. This article reviews the current literature on EDC effects on the neuroendocrine system, particularly at the level of hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the key cells involved in the regulation of reproductive function. The focus of this article is on two polychlorinated biphenyl mixtures (Aroclor 1221, Aroclor 1254) and two organochlorine pesticides (methoxychlor and chlorpyrifos). Some experimental data are presented for each of the four urban environmental toxicants on GnRH cells in vitro and in vivo. The results of in vitro experiments indicate that all four of the toxicants profoundly affect hypothalamic GnRH gene expression, cell survival, and neurite outgrowth, demonstrating direct effects of EDCs on a GnRH cell line. In in vivo experiments, three of the toxicants (Aroclor 1221,methoxychlor, and chlorpyrifos) caused significant alterations in GnRH mRNA levels in female rats. Both the in vitro and in vivo findings support the novel concept of chlorpyrifos as an EDC. The results, taken together with the literature, support the hypothesis that the neuroendocrine axis, and specifically GnRH neurons, are sensitive to urban environmental toxicants, and that reproductive and neurologic effects of EDCs may be mediated at this level of the hypothalamic-pituitary-gonadal axis.
引用
收藏
页码:235 / 246
页数:12
相关论文
共 101 条
[91]   A ROLE FOR N-METHYL-D-ASPARTATE (NMDA) RECEPTORS IN THE CONTROL OF LH-SECRETION AND INITIATION OF FEMALE PUBERTY [J].
URBANSKI, HF ;
OJEDA, SR .
ENDOCRINOLOGY, 1990, 126 (03) :1774-1776
[92]   Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro [J].
Vinggaard, AM ;
Hnida, C ;
Breinholt, V ;
Larsen, JC .
TOXICOLOGY IN VITRO, 2000, 14 (03) :227-234
[93]   Screening of selected pesticides for oestrogen receptor activation in vitro [J].
Vinggaard, AM ;
Breinholt, V ;
Larsen, JC .
FOOD ADDITIVES AND CONTAMINANTS, 1999, 16 (12) :533-542
[94]  
vomSaal FS, 1997, P NATL ACAD SCI USA, V94, P2056
[95]   PURIFIED METHOXYCHLOR STIMULATES THE REPRODUCTIVE-TRACT IN IMMATURE FEMALE MICE [J].
WALTERS, LM ;
ROURKE, AW ;
EROSCHENKO, VP .
REPRODUCTIVE TOXICOLOGY, 1993, 7 (06) :599-606
[96]   INVIVO RELEASE OF LUTEINIZING-HORMONE RELEASING HORMONE INCREASES WITH PUBERTY IN THE FEMALE RHESUS-MONKEY [J].
WATANABE, G ;
TERASAWA, E .
ENDOCRINOLOGY, 1989, 125 (01) :92-99
[97]   ESTROGENIC ACTION OF DDT AND ITS ANALOGS [J].
WELCH, RM ;
LEVIN, W ;
CONNEY, AH .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1969, 14 (02) :358-&
[98]   DEVELOPMENTAL NEUROTOXICITY OF CHLORPYRIFOS - CELLULAR MECHANISMS [J].
WHITNEY, KD ;
SEIDLER, FJ ;
SLOTKIN, TA .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1995, 134 (01) :53-62
[99]  
WOOLLEY CS, 1992, J NEUROSCI, V12, P2549
[100]   A DEVELOPMENTAL-STUDY OF THE QUANTITATIVE DISTRIBUTION OF LHRH NEURONS WITHIN THE CENTRAL-NERVOUS-SYSTEM OF POSTNATAL MALE AND FEMALE RATS [J].
WRAY, S ;
HOFFMAN, G .
JOURNAL OF COMPARATIVE NEUROLOGY, 1986, 252 (04) :522-531