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Various clinical and epidemiological evidence strongly suggests a major role for sex steroid hormones in the determination of anatomical specificities of fat distribution in human. To date, no studies have examined the possible presence of androgen receptors (AR) in human adipocytes and preadipocytes. We have studied AR in preadipocytes from various anatomical locations (intra-abdominal and subcutaneous) in middle-aged men and women during the proliferation and differentiation processes (adipogenesis). Androgen binding sites quantified by [3H]R-1881-specific binding in whole cell extracts were twofold higher in intra-abdominal than in subcutaneous preadipocytes but identical for the same fat depots in men and women. Western blot analysis revealed 1) the presence of AR in the nuclear and cytosolic fractions of human preadipocytes, 2) a decrease of AR expression during adipogenesis, and 3) an upregulation of AR by androgens in vitro. RT-PCR experiments showed the presence of AR mRNA in human preadipocytes and adipocytes and also the regional specificity of AR distribution. However, AR mRNA expression was found to increase during adipogenesis. The same results were observed in rat preadipocytes. In conclusion, this study clearly demonstrates the presence of AR in human preadipocytes and adipocytes and suggests that androgens may contribute, through regulation of their own receptors, to the control of adipose tissue development.

Adipocytes are estrogen-responsive cells, but the quantitative expression and transcriptional regulation of the estrogen receptors (ER-alpha and ER-beta) in human adipocytes and their precursor cells are unclear. Using real-time quantitative PCR, we have demonstrated that both ER-alpha and ER-beta mRNA are expressed in human mature adipocytes with a large predominance of ER-alpha mRNA. Moreover, ER-alpha mRNA is identically expressed whatever the anatomic origin (intraabdominal and subcutaneous) of the adipocytes and the gender. ER-beta mRNA levels are higher in women compared with men, without regional differences. 17beta-Estradiol in vitro upregulates expression of both ER-alpha and ER-beta mRNA in subcutaneous adipocytes from women but only the ER-alpha mRNA in subcutaneous and intra-abdominal adipocytes from men. In preadipocytes, only the ER-alpha subtype was present. In the latter cells, estrogens in vitro had no influence on ER-alpha expression (mRNA and protein). The present study also shows that estrogens in vitro increase the AP-1, SP-1, and estrogen response element DNA binding activities in differentiated but not in confluent preadipocytes, suggesting that ER become functional during the course of adipogenesis. On the whole, these data are consistent with a predominant role of the ER-alpha subtype in mediating the effects of estrogens on human adipose tissue development and metabolism.