title: DHEA administration activates local bioactive androgen metabolism in cancellous site of tibia of ovariectomized rats.
abstract: It is not known whether local androgen metabolism is involved in the mechanisms underlying the dehydroepiandrosterone (DHEA) administration-induced improvement of bone mineral density (BMD) in an estrogen-deficiency state. The aim of the present study was to clarify whether DHEA administration would improve local androgen metabolism and BMD in cancellous site of tibia of ovariectomized (OVX) rats. Twenty-two female rats, 6 weeks old, were randomized into three groups: sham-operated rats, OVX control rats, and OVX rats that received DHEA treatment. DHEA was administered intraperitoneally at 20 mg/kg body weight for 8 weeks. The concentrations of free testosterone and dihydrotestosterone (DHT) in cancellous site of tibia did not change as a result of ovariectomy, while the DHT concentration increased following DHEA administration. We revealed that DHEA administration improved the reduction of 17β- and 3β-hydroxysteroid dehydrogenases and clearly reversed the reduction of 5α-reductase types 1 and 2 and androgen receptor in the cancellous site of tibia of OVX rats. DHEA administration suppressed estrogen deficiency relative to the decrease in the cancellous BMD, which was positively associated with local DHT concentration. These findings indicate that DHEA administration enhances local bioactive androgen metabolism in the cancellous tibia of young OVX rats, suggesting that local DHT may play a part in the DHEA administration-induced improvement of cancellous BMD.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Katsuji
authors.initials: K
authors.lastname: Aizawa
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Iemitsu
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Akimoto
authors.forename: Umon
authors.initials: U
authors.lastname: Agata
authors.forename: Seiji
authors.initials: S
authors.lastname: Maeda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ezawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Omi
mesh_terms: D000728:Androgens / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D010052:Ovariectomy; D019899:Paracrine Communication / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000728:Androgens; D003687:Dehydroepiandrosterone