title: Diethylstilbestrol decreased adrenal cholesterol and corticosterone in rats.
abstract: The synthetic oestrogen diethylstilbestrol (DES), which is known to bind oestrogen receptors (ERs), has been reported to have adverse effects on endocrine homeostasis; however, the molecular mechanisms underlying these effects are poorly understood. In this study, we treated rats with DES and found high levels of this compound in the liver, adrenal glands and pituitary gland, as compared with other tissues. We have also detected early adverse effects of DES in the adrenal glands. The adrenal glands of rats treated with DES (340 μg/kg body weight every 2 days) for 2 weeks showed increased weight and size and a decreased fat droplet size. Following 1 week of treatment with DES, the blood and adrenal corticosterone levels were substantially decreased without any histological alterations. The levels of the precursors for corticosteroid biosynthesis in the adrenal glands were also decreased, as determined using mass spectroscopy. Cholesterol, the principal material of corticosteroid biosynthesis, decreased substantially in the adrenal glands after only 1 week of treatment with DES. In conclusion, cholesterol insufficiency results in a reduction in adrenal corticosterone biosynthesis, which may lead to endocrine dysfunction, such as reproductive toxicity.
authors.affiliation: Laboratory of Veterinary Biochemistry Laboratory of Veterinary Pathology Laboratory of Veterinary Anatomy, School of Veterinary Medicine Laboratory Animal Nutrition, School of Veterinary Science, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan Japan Meat Science and Technology Institute, Ebisu, Shibuya-ku, Tokyo 150-0013, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Haeno
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Maeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
authors.forename: Sachi
authors.initials: S
authors.lastname: Tahata
authors.forename: Michiko
authors.initials: M
authors.lastname: Sato
authors.forename: Kanako
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ueda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000311:Adrenal Glands / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000009:adverse effects*; D015536:Down-Regulation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000009:adverse effects*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D052244:Endocrine Disruptors; D011333:Pro-Opiomelanocortin; D004054:Diethylstilbestrol; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D003345:Corticosterone
keywords: adrenal insufficiency; cholesterol; corticosterone; diethylstilbestrol; endocrine disruptor