896 Androgens activate lipogenesis through an AKT-independent mTOR pathway stimulation and a limitation of autophagy in an androgen-sensitive sebocyte cell line

Androgens are key regulators of sebaceous function. We previously showed that DHT clearly induced the lipogenic differentiation of androgen-sensitive sebocytes, this in defined medium without any factor or specific metabolic complementation (1). Here we demonstrate that this DHT-induced lipid synthesis/storage is in part mediated by the activation of the mTOR pathway. The mTOR inhibitors rapamycin and torin inhibit lipid neosynthesis and storage in DHT-treated cells; conversely, DHT stimulates mTOR pathway, independently of AKT activation and signaling. We also show that, as a corollary of mTOR stimulation, DHT decreases the autophagic flow. This work experimentally links the (already described) implications of mTOR and autophagic processes in sebaceous function to androgenic stimulation and highlights the potential interest of mTOR inhibitors for the modulation of androgen-dependent sebum overproduction. (1) Barrault et al. (2015) J Steroid Biochem Mol Biol ;152:34-44