THE HUMAN SEBOCYTE CULTURE MODEL PROVIDES NEW INSIGHTS INTO DEVELOPMENT AND MANAGEMENT OF SEBORRHEA AND ACNE

Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro m odels. The human se bocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they u ndergo an incomplete terminal differentiation in vitro. In vitro synth esis of free fatty acids without bacterial involvement and marked inte rleukin 1 alpha expression at the mRNA and protein levels with no furt her induction by Lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androg ens affected sebocyte activity in vitro in a manner dependent on the l ocalization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolac tone. Cultured sebocytes strongly expressed type 1 5 alpha-reductase a nd metabolized testosterone to androstenedione, 5 alpha-androstanedion e, 5 alpha-dihydrotestosterone, androsterone and 5 alpha-androstanedio l, whereas the levels of 5 alpha-reductase activity were probably not feedback regulated. 4,7 beta-Dimethyl-4-aza-5 alpha-cholestan-3-one, a type 1 5 alpha-reductase inhibitor, induced an early, marked down-reg ulation of 5 alpha-reductase activity in human se bocytes in vitro, wh ile hydrofinasteride, a type 2 inhibitor required 10(3)-fold higher co ncentrations to induce similar effects. Stimulation of sebocyte prolif eration by insulin, thyroid-stimulating hormone and hydrocortisone ind icates that the hormonal control of the sebaceous gland could be a com plex mechanism. Retinoids inhibited sebocyte proliferation in a dose-d ependent manner and down-regulated lipid synthesis and sebocyte differ entiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and di fferentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte prolifer ation was barely affected by the presence of vitamin A. The low persis tent isotretinoin levels or, more likely, the considerably elevated tr etinoin concentrations detected in human sebocytes after treatment wit h isotretinoin in vitro may be responsible for the inhibitory effect o f this compound on sebocyte activity.