title: Effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on serum androgens and steroidogenic enzyme activities in the male rat reproductive tract.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to impair reproductive function of males in animal models, possibly due to a reduction in serum androgen levels. Thus, TCDD may alter the testosterone biosynthetic pathway in the testis or the conversion of testosterone to 5alpha-dihydrotestosterone (DHT) in androgen target tissues. Pregnant Sprague Dawley rats were gavaged with TCDD (0, 0.2 or 1.0 microg/kg) on day 15 of gestation only. TCDD caused a reduction in the body weight gain of the dams in both dose groups and a significant reduction in litter size in the higher dose group. Litters delivered normally and TCDD exposed male offspring grew at the same rate as controls. Males were sacrificed at 15, 30, 45, 60, 90 and 120 d of age. Steroidogenic enzyme activities were determined in testicular microsomes and androgen target tissue nuclear fractions. Serum androgens were measured by radioimmunoassay (RIA). At 30 d of age, rats exposed to 1.0 microg/kg TCDD exhibited lower 17-hydroxylase activity (P < 0.05) and lower caput-corpus epididymal weights (P < 0.05). At 45 d of age, the same treatment resulted in testicular 3beta-HSD, 17beta-HSD and 5alpha-reductase activities that were significantly greater (P < 0.05) but, conversely, serum androgens were one quarter the values evident in controls (P < 0.05). At the other ages, no differences were observed in serum androgens and, with the exception of lower 17beta-HSD activity at 90 d of age (P < 0.05), no other differences in testicular steroidogenic enzyme activities were found. 5Alpha-reductase activities in the androgen target tissues were also unchanged. Histological examination of testes showed that the spermatogenic profile was identical to controls at all ages.
authors.affiliation: Health Canada, and Department of Cellular and Molecular Medicine, University of Ottawa, Banting Research Centre, Ont. gerard_cooke@hc-sc.gc.ca
authors.forename: G M
authors.initials: GM
authors.lastname: Cooke
authors.forename: C A
authors.initials: CA
authors.lastname: Price
authors.forename: R J
authors.initials: RJ
authors.lastname: Oko
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000728:Androgens / Q000097:blood*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase; D005260:Female; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D007774:Lactation; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000728:Androgens; D000072317:Polychlorinated Dibenzodioxins; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D042944:Cholestenone 5 alpha-Reductase