Jarry Hubertus, Metten Maria, Gamer Armin O, Wuttke Wolfgang
Abteilung für klinische und experimentelle Endokrinologie, Universitätsfrauenklinik Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Arch Toxicol. 2002 Nov;76(11):657-63. doi: 10.1007/s00204-002-0386-y. Epub 2002 Aug 10.
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.
在多项研究中,已描述了接触苯乙烯的工人垂体激素催乳素(PRL)分泌过多的情况。这会导致诸如月经过少、继发性闭经和生育能力下降等生殖问题[阿尔菲尼等人(1987年)《职业医学杂志》29:826 - 830,贝加马斯基等人(1996年)《神经毒理学》17:753 - 760,穆蒂和斯马尔贾西(1998年)《毒理学与工业卫生》14:311 - 323]。PRL的分泌受到下丘脑神经元释放的儿茶酚胺多巴胺(DA)的紧张性抑制。有人提出,血清中多巴胺-β-羟化酶(DBH)的活性是中枢多巴胺能功能的外周标志物。在接触苯乙烯的工人中观察到这种酶活性略有降低,这与PRL分泌过多有关。为了进一步研究苯乙烯对PRL释放的假定影响,将雄性大鼠连续5天每天暴露于苯乙烯蒸气(645、2150和6450毫克/立方米)中6小时。在最后一次暴露后立即处死动物(即时组)或在恢复24小时后处死(恢复组)。通过放射免疫测定法测量血清PRL和DA水平。采用高效液相色谱 - 电化学检测法测定纹状体和中基底下丘脑(MBH)中儿茶酚胺及其代谢产物的浓度。在即时组和恢复组中均未观察到血清PRL水平有任何统计学上的显著变化。同样,纹状体和MBH中儿茶酚胺及其代谢产物的浓度也未受影响。从这些数据我们得出结论,即使在非常高的浓度下,苯乙烯对调节大脑中PRL释放和DA水平的神经内分泌机制也没有不良影响。考虑到任何动物模型都存在的固有局限性,我们认为我们的数据表明苯乙烯对人类也没有不良神经内分泌影响。