Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women.
OBJECTIVE
Leptin, a product of adipocytes, is a cytokine with multiple effects on the reproductive axis. Leptin causes the activation of STAT proteins within target cells. The aromatase gene promoter in adipose stromal cells contains a functional STAT binding region, leading to the hypothesis that leptin may regulate aromatase activity in fat tissue. To test this hypothesis, adipose stromal cells were isolated from subcutaneous abdominal fat or breast fat then placed into tissue culture.


METHODS
The cells were treated for three days with increasing concentrations of recombinant human leptin. Aromatase activity in the stromal cells was measured by the release of 3H2O from radiolabeled androstenedione precursor.


RESULTS
Basal aromatase activity varied markedly between, but there were no differences between abdominal fat and breast fat. Leptin concentrations in the physiological range of normal weight or thin women (10 ng/ml) had no effect on aromatase activity. In 2 of 8 abdominal fat cultures and 1 of 2 breast fat cultures, a high obese concentration of leptin (100 ng/ml) stimulated a significant increase in aromatase activity. In the remaining subjects there was no effect of leptin, even at high concentrations.


CONCLUSIONS
These data demonstrate that in approximately 30 percent of our subject population leptin was able to stimulate aromatase activity in adipose stromal cells at high concentrations. The elevated levels of aromatase activity may contribute to increase circulating estrogen levels in certain obese women and suggest that elevated leptin concentrations in obese women may cause locally elevated estrogen concentrations in the breast and thereby promote tumor formation.
Magoffin
D A
DA
Department of Obstetrics and Gynecology, CSMC Burns and Allen Research Institute, UCLA School of Medicine 90048, USA.
Weitsman
S R
SR
Aagarwal
S K
SK
Jakimiuk
A J
AJ
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000737:chemistry; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology*; D004967:Estrogens / Q000032:analysis; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D017154:Stromal Cells / Q000378:metabolism*
D016207:Cytokines; D004967:Estrogens; D001141:Aromatase