Prenatal Aroclor 1254 exposure and brain sexual differentiation: effect on the expression of testosterone metabolizing enzymes and androgen receptors in the hypothalamus of male and female rats.
Polychlorinated biphenyls (PCBs) are industrial pollutants detected in human milk, serum and tissues. They readily cross the placenta to accumulate in fetal tissues, particularly the brain. These compounds affect normal brain sexual differentiation by mechanisms that are incompletely understood. The aim of this study was to verify whether a technical mixture of PCBs (Aroclor 1254) would interfere with the normal pattern of expression of hypothalamic aromatase and 5-alpha reductase(s), the two main enzymatic pathways involved in testosterone activation and of androgen receptor (AR). Aroclor 1254 was administered to pregnant rats at a daily dose of 25 mg/kg by gavage from days 15 to 19 of gestation (GD15-19). At GD20 the expression of aromatase, 5-alpha reductase types 1 and 2 and androgen receptor (AR) and aromatase activity were evaluated in the hypothalamus of male and female embryos. The direct effect of Aroclor was also evaluated on aromatase activity adding the PCB mixture to hypothalamic homogenates or to primary hypothalamic neuronal cultures. The data indicate that aromatase expression and activity is not altered by prenatal PCB treatment; 5-alpha reductase type 1 is similarly unaffected while 5-alpha reductase type 2 is markedly stimulated by the PCB exposure in females. Aroclor also decreases the expression of the AR in females. The observed in vivo effects are indicative of a possible adverse effect of PCBs on the important metabolic pathways by which testosterone produces its brain effects. In particular the changes of 5-alpha reductase type 2 and AR in females might be one of the mechanisms by which Aroclor exposure during fetal development affects adult sexual behavior in female rats.
Colciago
A
A
Institute of Endocrinology, Via Balzaretti, Milano, Italy.
Negri-Cesi
P
P
Pravettoni
A
A
Mornati
O
O
Casati
L
L
Celotti
F
F
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D013956:Antithyroid Agents / Q000008:administration & dosage / Q000633:toxicity; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine) / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012733:Sex Differentiation / Q000187:drug effects*; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000187:drug effects
D013956:Antithyroid Agents; D007527:Isoenzymes; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D020111:Chlorodiphenyl (54% Chlorine); D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase