Androgen regulation of the insulin-like growth factor-I and the estrogen receptor in rat uterus and liver.
For the first time testosterone is shown to be an important regulator of the insulin-like growth factor-I (IGF-I) in the rat uterus under in vivo conditions. In this study the regulation of IGF-I and the estrogen receptor (ER) by gonadal steroids in the uterus and liver of female rats was monitored. The ER level was assayed by hormone binding after treatment with testosterone, 5 alpha-dihydrotestosterone or estradiol and specific mRNA species were analyzed by a solution hybridization/RNase protection assay using 35S-labeled RNA probes. Ovariectomized rats restored uterine weight after treatment with testosterone. Uterine IGF-I mRNA was more than 20-fold higher in testosterone treated rats compared to untreated ovariectomized controls after 48 h treatment. The effects of testosterone on ovariectomized animals was followed in a timecourse study. Testosterone administration increased uterine IGF-I mRNA expression during the first 48 h and the maximally induced level was maintained throughout the duration of the experiment (168 h). Since induction of IGF-I mRNA by estrogen is transient, these data indicate that androgen and estrogen increase IGF-I mRNA by different mechanisms. Regulation of IGF-I mRNA by gonadal steroids was also studied in hypophysectomized animals. The rats were given either testosterone, 5 alpha-dihydrotestosterone or estradiol, and uterine IGF-I mRNA was measured after 1 week of treatment. At this timepoint estrogen treated rats showed levels of IGF-I mRNA not significantly different from those of hypophysectomized controls. In contrast testosterone and 5 alpha-dihydrotestosterone increased the IGF-I mRNA level 30 and 40 times, respectively, relative to hypophysectomized control animals. Since 5 alpha-dihydrotestosterone is not convertable to estrogen, the induction by testosterone was considered to be a true androgenic phenomenon.
Sahlin
L
L
Division for Reproductive Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Norstedt
G
G
Eriksson
H
H
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D013739:Testosterone / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D000728:Androgens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I