The improved organ maintenance of the human sebaceous gland: modeling in vitro the effects of epidermal growth factor, androgens, estrogens, 13-cis retinoic acid, and phenol red.
We have previously reported that human sebaceous glands can be maintained for up to 14 d as whole organs with full retention of the physiological rate and pattern of new cell formation, but we have also reported that the newly formed cells did not differentiate normally, causing a progressive loss of lipogenesis in vitro. We now show that this abnormal sebocyte differentiation was attributable to the presence of epidermal growth factor (EGF) and phenol red in our maintenance medium. In their absence, human sebaceous glands apparently retain in vivo rates of cell division and lipogenesis over 7 d of maintenance in addition to a retention of in situ morphology. This is reversible on the re-addition of 10 ng EGF/ml and 10 mg phenol red/ml. The addition of 600 pM 17 beta-estradiol results in a significant fall in the rate of lipogenesis over 7 d of maintenance, without affecting the rate of cell division. This effect is apparently due to abnormal differentiation of newly formed sebocytes. Neither 1 nM testosterone nor 1 nM dihydrotestosterone (DHT) has any effect on rates of cell division of lipogenesis over 7 d. In the presence of phenol red, however, 1 nM testosterone or 1 nM DHT cause a significant reduction in the rate of lipogenesis over 7 d of maintenance. One micromolar 13-cis retinoic acid caused a significant reduction in the rate of lipogenesis over 7 d in both the presence and absence of phenol red. These findings show that we can model the physiological effects of steroids, EGF, and 13-cis retinoic acid in vitro.
Guy
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R
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, U.K.
Ridden
C
C
Kealey
T
T
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D013196:Dihydrotestosterone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009924:Organ Culture Techniques; D010637:Phenolsulfonphthalein / Q000494:pharmacology; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology
D003470:Culture Media; D008055:Lipids; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D015474:Isotretinoin; D010637:Phenolsulfonphthalein