Effects of a 5-day treatment with vinclozolin on the hypothalamo-pituitary-gonadal axis in male rats.
Vinclozolin (VZ), a potent antiandrogenic fungicide, is known to interfere with male reproductive function. Little data are currently available regarding possible impacts of VZ on brain function, particularly neuroendocrine activity and regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Therefore, we examined the effects of VZ on gene expression in the brain (MBH/ME, MPOA/AH, striatum, hippocampus), pituitary, prostate, seminal vesicles, and epididymis of 4-month-old male rats treated daily by gavage for 5 days with VZ (150 mg/kg body weight/day). Alterations in levels of serum hormones and gene expression were determined by RIA and qRT-PCR, respectively. Our results revealed that (i) VZ decreases epididymis weights, increases serum levels of LH and T, and decreases serum TSH and total T(4) levels; (ii) VZ affects the hypothalamic expression of both estrogen receptor (ERs) subtypes, ERalpha and ERbeta; (iii) in the extrahypothalamic brain areas, VZ alters expression of ERs and androgen receptor (AR); (iv) in the pituitary, VZ up-regulates expression of the GnRH receptor, LHbeta, alpha-subunit, and TERP-1/-2; (v) in the ventral prostate, VZ increases and decreases levels of AR and ERbeta mRNA, respectively; (vi) in the seminal vesicles, VZ increases levels of AR and ERalpha mRNA expressions; (vii) in the epididymis, VZ up-regulates AR and ERbeta mRNA expression. These results indicate that in vivo VZ is not a 'pure' antiandrogen, since it exerts mixed AR antagonistic/ERs agonistic actions observed at the levels of mRNA expression of selected androgen- and estrogen-regulated genes in the CNS, pituitary, and male accessory sex organs.
Loutchanwoot
Panida
P
Department of Endocrinology, Faculty of Medicine, University of Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.
Wuttke
Wolfgang
W
Jarry
Hubertus
H
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D004334:Drug Administration Schedule; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005837:Genitalia, Male / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006728:Hormones / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010080:Oxazoles / Q000633:toxicity*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000726:Androgen Antagonists; D006728:Hormones; D010080:Oxazoles; C025643:vinclozolin