In vivo and in vitro ob gene expression and leptin secretion in rat adipocytes: evidence for a regional specific regulation by sex steroid hormones.
As a sexual dimorphism appears in plasma leptin levels, the aim of the present study was to investigate, in vivo and in vitro, the influence of sex steroid hormones on ob messenger RNA (mRNA) and leptin expressions in rat fat cells from various anatomical localizations. In male rats, castration resulted in a modulation of ob gene mRNA expression which was increased by 2-fold in perirenal and half-reduced in sc adipocytes. Moreover, in isolated fat cells from both perirenal and s.c. fat depots, ob gene mRNA expression was reduced by 20% after a 24-h in vitro exposure to dihydrotestosterone (10(-8) M). This effect of dihydrotestosterone on ob mRNA was prevented by exposure to the antiandrogen cyproterone acetate and also by actinomycin D. In contrast, leptin secretion from both perirenal and sc adipocytes was unchanged after 24 h exposure to dihydrotestosterone. In female rats, ovariectomy induced a 25% decrease in ob gene mRNA expression in perirenal fat cells. In vitro studies revealed that a 24-h exposure to 17-beta estradiol (10(-8) M) induced a 1.4-, 1.2-, and 1.75-fold increase in ob mRNA expression and a 3.8-, 1.65- and 2-fold increase in leptin secretion in sc, perirenal and parametrial adipocytes, respectively. Moreover, these effects were prevented by the antiestrogen ICI182780 and also by actinomycin D. Altogether, these results demonstrate that in rat adipocytes, estrogens, and androgens modulate ob gene expression at the mRNA level through sex steroid receptor-dependent transcriptional mechanisms.
Machinal
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F
INSERM CJF 94-02, Faculté de Médecine Paris-Ouest, Université Descartes (Paris V) Centre Hospitalier de Poissy, France.
Dieudonne
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MN
Leneveu
M C
MC
Pecquery
R
R
Giudicelli
Y
Y
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D020738:Leptin; D008297:Male; D009765:Obesity / Q000235:genetics*; D009919:Orchiectomy; D010052:Ovariectomy; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012739:Gonadal Steroid Hormones; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D004958:Estradiol