Growth Hormone and Insulin-Like Growth Factors Have Different Effects on Sebaceous Cell Growth and Differentiation

Abstract

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.

Beyond acne: Current aspects of sebaceous gland biology and function

“…Increased serum levels of IGF-I have been observed in adult women and men with acne and the number of total acne lesions, inflammatory lesions, serum levels of 5α-DHT and dehydroepiandrosterone sulphate (DHEAS), each correlated with serum IGF-I levels in women with acne [90]. IGF-I plays a key role in the induction of lipid synthesis in human sebocytes [91,92]. IGF-I increases lipogenesis by inducing SREBP-1 [50] through activation of PI3K/Akt and MAPK/ERK-signal transduction pathway [93].…”

An update on the role of the sebaceous gland in the pathogenesis of acne

“…53 The expression of IGF-I receptor mRNA is the strongest in basal cells of sebaceous glands and immature sebocytes, whereas IGF-I receptor protein expression was uniform and intense in all regions of the gland. 53 In animal studies, IGF-I has been shown to stimulate sebocyte differentiation in vitro especially in combination with GH, 47 while in human keratinocytes it acts as a mitogen. 54 On the other hand, in humans, IGF-I plays a key role in the induction of lipid synthesis in human sebocytes.…”

“…46 In acne vulgaris, increased sebum production peaks in mid-adolescence at a time that GH and IGF-I reach their highest serum levels. 47 In mini rats, suppression of GH gene expression by an antisense transgene, leads among to thinner skin with less collagen and increase of subcutaneous adipose tissue also to small-sized sebaceous glands. 48 Increased serum levels of IGF-I have been observed in adult women and men with acne and the number of total acne lesions, inflammatory lesions, serum levels of 5α-DHT and DHEA sulphate, each correlated with serum IGF-I levels in women with acne.…”

Skin and brain age together: The role of hormones in the ageing process

“…Moreover, IGF-I has been shown to stimulate sebocyte differentiation in vitro especially in combination with GH (Deplewski and Rosenfield, 1999), while in human keratinocytes it acts as a mitogen (Tavakkol et al, 1999). In acne vulgaris, increased sebum production peaks in mid-adolescence at a time that GH and IGF-I reach their highest serum levels (Deplewski and Rosenfield, 1999).…”

“…In acne vulgaris, increased sebum production peaks in mid-adolescence at a time that GH and IGF-I reach their highest serum levels (Deplewski and Rosenfield, 1999). IGF-I amplified lipid synthesis in SZ95 sebocytes and fibroblasts as well as fibroblast proliferation, all in a dose-dependent manner underlining the fact that the declining IGF-I levels with increasing age may play a significant role in the reduction of skin surface lipids and thickness (Makrantonaki et al, 2008).…”