Sex steroids and leptin regulate 11beta-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: Sex specificities.
Adipose tissue is an important site of steroid hormone biosynthesis, as type I 11beta-hydroxysteroid dehydrogenase (HSD1), the enzyme responsible for the conversion of cortisone into cortisol and the P450 aromatase, the enzyme catalysing androgens aromatization into estrogens, are both expressed in human adipose tissue. In the present report, we have investigated the possibility that sex steroids and leptin could regulate these two enzymes in cultured preadipocytes from men and women intra-abdominal fat depots. In women preadipocytes, human recombinant leptin down-regulates HSD1 mRNA expression (-58%) and P450 aromatase activity (-26%). Conversely, leptin up-regulates the HSD1 (2.4-fold) and the P450 aromatase (1.6-fold) mRNA expression in men preadipocytes. In women preadipocytes, 17beta-estradiol strongly stimulates HSD1 mRNA expression (10-fold) and, in contrast, decreases by half the P450 aromatase expression. In men, 17beta-estradiol has no influence on HSD1 expression but up-regulates P450 aromatase mRNA expression (2.4-fold). Finally, androgens increase by a factor of 2.5-5 the mRNA expression of both enzymes in men. These findings suggest that sex steroids and leptin either increase or decrease local cortisol and estrogens productions in men or in women preadipocytes, respectively. They also indicate that steroid metabolism in adipose tissue is controlled by a coordinated regulation of P450 aromatase and HSD1 expressions. Finally, the important sex-specific differences described herein may also contribute to explain the sexual dimorphism of body fat distribution in humans.
Dieudonné
Marie-Noëlle
MN
Service de Biochimie et de Biologie Moléculaire, UPRES EA 2493, Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex, France.
Sammari
Anes
A
Dos Santos
Esther
E
Leneveu
Marie-Christine
MC
Giudicelli
Yves
Y
Pecquery
René
R
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D017667:Adipocytes / Q000201:enzymology*; D000273:Adipose Tissue / Q000201:enzymology*; D000368:Aged; D001141:Aromatase / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D017697:Premenopause; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics
D017931:DNA Primers; D012739:Gonadal Steroid Hormones; D020738:Leptin; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D001141:Aromatase