Growth Factors and Neuropeptides

EGF, TGF-a, basic FGF, and keratinocyte growth factor (KGF) all inhibit lipogenesis and with the exception of KGF are mitogenic in cultured hamster sebocytes (133,151). In organ culture of human sebaceous glands, EGF produced a dose-dependent inhibition of lipid synthesis and inhibited DNA synthesis (152), and removal of EGF from the medium caused an increase in the rate of lipogenesis without affecting cell turnover (113). In vivo, the presence of EGF inhibited the sebaceous gland differentiation in sheep (153), and in hamster ears, it stimulated the sebaceous glands to proliferate (154). Receptors for EGF are found in sebaceous glands (155). Based on this evidence, Kealey and colleagues proposed that EGF may be, in part, responsible for sebaceous gland atrophy observed during acne lesion formation (7,152). EGF can also induce changes in sebum composition. Ridden (156), reported that there was a fall in the amount of squalene and a corresponding rise in cholesterol, although this was not corroborated by other researchers (157).

Sebocyte proliferation is stimulated by insulin, thyroid-stimulating hormone, and hydrocortisone (158). In rat preputial cells, growth hormone (GH) increased sebocyte differentiation and was more potent than either insulin-like growth factors (IGFs) or insulin. Furthermore, GH enhanced the effect of DHT on sebocyte differentiation perhaps complementing the effect of androgens in increasing sebum during puberty. IGFs, in contrast, had a greater effect on increasing DNA synthesis compared to GH, and had no effect on the response of the cell to DHT (159), although a role for IGF in causing the observed increase in sebum production at puberty has not been ruled out. This suggests that antagonists of IGF may offer a way of decreasing sebum synthesis.

Corticotrophic-releasing hormone (CRH), a key regulator in the central nervous system, has been implicated in sebum production (160). CRH and its receptor are expressed in cultured sebocytes, where the hormone appears to upregulate expression of 3 b-HSD—a key enzyme in the androgen biosynthetic pathways. Therefore, CRH could indirectly influence lipid synthesis by modifying the local production of androgens.

Incubation of sebaceous glands in organ culture with neuropeptides (e.g., calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide, or neuropeptide Y), or NGF up to a final concentration of 10~7M showed that only substance P had any effect on sebaceous gland ultrastructure as observed in the electron microscope, and this effect was dose dependent (161). Skin samples cultured with substance P showed sebaceous glands with an increased gland area (in sections) compared with control samples. The sebocytes were engorged with numerous lipid droplets.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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