The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women.
OBJECTIVE
To investigate (1) whether type 3 17beta-hydroxysteroid dehydrogenase (17beta-HSD), the enzyme which catalyzes the conversion of androstenedione to testosterone in the testis, is co-expressed with P450aromatase in the preadipocytes of women, and (2) whether the relative expression of type 3 17beta-HSD and aromatase varies in subcutaneous abdominal vs intra-abdominal adipose tissue of women.


METHODS
Subcutaneous abdominal and intra-abdominal adipose tissue was obtained from women undergoing elective abdominal surgery (age 22-78 y, body mass index (BMI) 22.4-52.9 kg/m(2)).


METHODS
Expression of type 3 17beta-HSD in adipose cell fractions was determined using RT-PCR. Preadipocyte steroidogenesis was investigated in primary cultures using androstenedione as substrate. Messenger RNA levels for type 3 17beta-HSD and aromatase were measured in adipose tissue from the subcutaneous abdominal and intra-abdominal depots using a quantitative multiplex competitive RT-PCR assay.


RESULTS
Type 3 17beta-HSD is co-expressed with aromatase in the abdominal preadipocytes of women. Cultured preadipocytes from both subcutaneous abdominal (n=5) and intra-abdominal (n=5) sites converted androstenedione to testosterone, and there was minimal conversion of androstenedione to estrone. Consistent with this, the levels of type 3 17beta-HSD mRNA were significantly higher than aromatase mRNA at both sites (P<0.05; n=8 subcutaneous abdominal, n=12 intra-abdominal adipose tissue). The ratio of levels of 17beta-HSD mRNA to aromatase mRNA in intra-abdominal adipose tissue was positively correlated with BMI (n=11, r=0.61, P<0.05) and waist circumference (n=10, r=0.65, P<0.05). The converse was found in subcutaneous abdominal adipose tissue.


CONCLUSIONS
The intra-abdominal adipose tissue of women may be substantially androgenic, increasingly so with increasing obesity, particularly central obesity. While androgen production by this adipose tissue deposit may not contribute to circulating testosterone levels due to hepatic clearance, it may have hitherto unrecognised local effects in the intra-abdominal adipose tissue and also on the liver via the hepatic portal system. These studies suggest a mechanism linking central obesity with insulin resistance and dyslipidaemia.
Corbould
A M
AM
Department of Medicine, Flinders University of South Australia, Bedford Park, South Australia, Australia. acorbould@rics.bwh.harvard.edu
Bawden
M J
MJ
Lavranos
T C
TC
Rodgers
R J
RJ
Judd
S J
SJ
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D000005:Abdomen; D017667:Adipocytes; D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D015992:Body Mass Index; D017931:DNA Primers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin
D017931:DNA Primers; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase