Adipose tissue-dependent regulation of steroidogenesis

The importance of adipose tissue as a highly active endocrine organ has been revealed in the last years. Adipose tissue secretes a high variety of bioactive factors which mediate the crosstalk between adipose tissue and target organs. Several lines of evidence suggest an interaction between adipose tissue and the adrenal gland.

We have recently observed a direct stimulatory effect on adrenal steroidogenesis by human adipocytes. Adipocyte-derived factors have a strong stimulatory effect on aldosterone, cortisol and DHEA release from both human and bovine adrenocortical cells. This stimulation was dose dependent and the maximal stimulation was comparable to the maximal stimulation of the cells with forskolin (10–5M) or angiotensin II (10–7M). Aldosterone concentrations in the culture medium did not significantly increase before 12h of incubation indicating a long-term effect. The effect depends on at least 2 factors: a high molecular weight (>50kD) protein and a low molecular (<3kD) non-protein factor, interacting in the stimulation of steroidogenesis. In addition to a direct stimulatory effect on steroidogenesis by the high molecular weight fraction, we observed a sensitisation of angiotensin II-mediated cortisol and aldosterone release induced by the low molecular factor. This sensitisation effect was specific for angiotensin II-mediated steroidogenesis, but did not affect forskolin-induced secretion of cortisol and aldosterone secretion. Interestingly, the low molecular weight fraction per se had no direct effect on adrenal steroidogenesis.

These data indicate that adipose tissue regulates steroidogenesis by a direct stimulation of adrenal steroid secretion mediated by adipocyte-derived high molecular weight proteins and indirectly by a sensitisation of adrenocortical cells towards angiotensin II-mediated adrenal hormone secretion.