Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation

Several observations suggest that GH stimulates sebaceous gland growth and development. Therefore, we studied the effects of GH and insulin-like growth factors (IGFs), alone and with androgen, on sebaceous epithelial cell (sebocyte) growth and differentiation in vitro. The rat preputial cell culture model system was used to judge differentiation (induction of lipid-forming colonies, LFCs) and DNA synthesis. GH increased sebocyte differentiation. At a dose of 10(-8) M in the presence of micromolar insulin, GH was 3.8 times more potent than IGF-I (38.1+/-4.2%, SEM, vs. 10+/-1.5% LFCs) and 6 times more potent than IGF-II (6+/-0.5% LFCs). IGF-I 10(-8) M alone stimulated a similar amount of differentiation as insulin 10(-6) M, although it was less effective than insulin in augmenting the effect of GH on differentiation. GH had no effect on sebocyte uptake of 3H-thymidine at doses up to 10(-6) M. On the other hand, IGF-I was the most potent stimulus of DNA synthesis (168% of control; P < 0.001 vs. all others). IGF-II 10(-8) M stimulated 3H-thymidine incorporation similarly to insulin 10(-6) M. In the presence of insulin, dihydrotestosterone (DHT) 10(-6) M induced 31.4+/-1.7% LFCs, and there was a tendency of DHT and GH to interact in promoting differentiation. When insulin was omitted from the system, differentiation was decreased overall, but GH +/- DHT slightly improved differentiation. The IGFs had no effect on the response to DHT. DHT decreased DNA synthesis by 40%, an effect unaltered by GH or IGFs. These results suggest that GH and IGFs have different functions in sebaceous cell growth and differentiation: GH stimulated differentiation beyond that found with IGFs or insulin, yet had no effect on DNA synthesis, a parameter stimulated most potently by IGF-I. While GH augmented the effect of DHT on differentiation, the IGFs had no effect on the response of DHT. These data indicate that GH may in part act directly on sebocytes rather than indirectly through IGF production. These data are consistent with the concept that increases in GH and IGF production contribute in complementary ways to the increase in sebum production during puberty and in acromegaly.