Slc10a6, also known as the sodium-dependent organic anion transporter (SOAT), specifically transports 3'- and 17'-monosulfated steroid hormones, like estrone sulfate and dehydroepiandrosterone sulfate, into target cells [1]. These sulfo-conjugated steroids are inactive in the blood but serve as precursors for intracrine formation of active estrogens and androgens, contributing to steroid regulation in peripheral tissues. It is part of the SLC10 family and has a role in the intracrine mechanisms of sex steroid formation in tissues such as adipose tissue and testis [1,2,3]. Genetic models, like knockout mice, can help in understanding its function.

In Slc10a6 -/- knockout mice, normal spermatogenesis and reproduction were observed, despite high expression of SOAT in testicular germ cells and its supposed role in spermatogenesis [3]. However, male knockout mice had significantly higher serum cholesterol sulfate levels [3]. In adipose tissue of Slc10a6 -/- knockout mice, adipocytes increased in size in certain adipose depots, suggesting adipocyte hypertrophy, while serum adipokine levels were comparable to wild-type mice [2]. In 3T3-L1 adipocytes, Slc10a6-mediated uptake of DHEAS reduced lipid accumulation, but in knockout mice, its deletion induced adipocyte hyperplasia through unknown mechanisms [2].

In conclusion, Slc10a6 plays a crucial role in the transport of sulfated steroids, contributing to sex steroid intracrinology in adipose tissue and potentially other peripheral tissues. The gene knockout mouse models have provided insights into its role in adipose tissue adipogenesis and in the context of testicular function, though its exact contribution to spermatogenesis remains unclear. These findings may have implications for understanding steroid-responsive diseases such as hormone-dependent breast cancer [1].