Sebaceous fatty acids and alcohols are also distinguished by chain branching.

Methyl branches can occur on the next to last (penultimate) carbon of a fatty acid chain (iso branching), on the third from the last (anteiso (antepenultimate) carbon

ologically significant. Although the most powerful androgens are testosterone and its end-organ reduction product dihydrotestosterone, of sebaceous gland levels of tesFor tosterone do not parallel the patterns activity. example, testosterone levels are manyfold higher in males than in females, with no overlap between the sexes, whereas males average than in overlap rates of sebum with the secretion are only slightly higher in females, between considerable

ceptors; however, it has greater sebosuppressive action than does all-trans or 9-cis retinoic acid. 17 The mechanism by which 13-cis retinoic acid lowers sebum secretion is unknown, but it inhibits the 3a-hydroxysteroid activity of retinol dehydrogenase and leads to decreased arrest in androgen human cell synthesis.18 sebocytes models in In and of addition, isotretinoin triggers cell cycle immortalized also induces cell culture

branching), or on any even-numbered carbon (internal branching). Examples of these unusual unsaturated and branchedchain moieties are included in the lipid structures shown in Fig. 77-3.

human sebocytes (SZ95 and SEB-1) and apoptosis cycle SEB-1 and sebocytes.19-21 Inhibition synthesis, explain the of androgen arrest, of

The

Function of Sebum
precise is

groups. Also, sebum secretion starts to of It sebum has in increase in children during adrenarche, a developmental event that precedes puberty by approximately 2 years. The (DHEAS) weak might adrenal be a androgen sulfate significant dehydroepiandrosterone

function

humans acne.
1

unknown.

been

apoptosis by 13-cis retinoic acid may reduction sebaceous gland size after treatment.

proposed that its sole role is to cause The suggestion has been made that sebum reduces water loss from the skin's surface and functions to keep skin soft and smooth, although evidence for these claims in humans is minimal; however, as demonstrated in the sebaceous gland-deficient mouse (Asebia) model, glycerol derived from triglyceride critical shown least for to by in hydrolysis in sebum is maintaining protect part the and it stratum skin from at

regulator of sebaceous gland activity through its conversion to testosterone and dihydrotestosterone in the sebaceous gland. Levels of DHEAS are high in newborns, are very low in 2to 4-year-old children, and start to rise when sebum secretion starts to increase. In adulthood, DHEAS levels show considerable individual variation but are only slightly higher in men than in women on the average. There is a decline in DHEAS levels in both sexes starting parallels in the early decline adulthood of sebum and secontinuing throughout life. This decline cretion. DHEAS is present in the blood in high concentration. The enzymes required to convert DHEAS to more potent androgens are present in sebaceous glands.15 These include 30hydroxysteroid hydroxysteroid dehydrogenase, dehydrogenase, 170and

Melanocortins stimulating

Mlelanocor tins

include

melanocyteand In

hormone hormone.

adrenocorticotropic

rodents, melanocortins increase sebum production. Transgenic mice deficient in the melanocortin-5 sebaceous receptor play a sebum receptor glands
22

have and The been

comeum hydration. 11 Sebum has been infection bacteria fungi,

hypoplastic reduced

production. has role

melanocortin-5 where it may

because

contains

identified in human sebaceous glands, in the modulation of sebum production. 23

immunoglobulin A, which is secreted from most exocrine glands.12 Vitamin E delivery to the upper layers of the skin protects the skin and its surface lipids from oxidation. Thus, sebum flow to the surface of the skin may provide the transit

Peroxisome ProliferatorActivated PPARs are orphan

forms of and heterodimers involved

nuclear receptors

FACTORS REGULATING SEBACEOUS GLAND SIZE AND SEBUM PRODUCTION

mechanism

necessary

for

that are similar to retinoid receptors in many ways. Each of these receptors with in a retinoid variety X of and and receptors to regulate the transcription genes processes, including lipid metabolism cellular proliferation PPAR-a, PPAR-8, differentiation.

Sebum production is continuous and is not controlled by neural mechanisms. The exact mechanisms underlying the regulation of human sebum production have not been glands and such defined. are as Clearly, by but other sebaceous androgens factors, receptors peroxisome regulated

5a-reductase. Each of these enzymes exists in two or more isoforms that exhibit tissue-specific differences in their expression. The predominant isozymes in the sebaceous gland include type dehydrogenase, Retinoids 13p-hydroxysteroid type 2 17p-

PPAR-y receptor sub-types have been detected in basal sebocytes. PPAR-y is also fibrates detected In in differentiated receiving for ligands) sebocytes. patients or

retinoids,

melanocortins, and fibroblast

proliferator-activated (PPARs),

Isotretinoin (13-cis retinoic acid) is the most potent pharmacologic inhibitor of sebum secretion. Significant reductions in sebum production can be observed as early as 2 weeks after use.16 Histologically, sebaceous glands are markedly reduced in size, the and charindividual sebocytes lacking appear

(PPAR-oc

hyperlipidemia secretion rates

thiazolidinediones increased. Rat

growth factor receptors (FGFRs) have been postulated to play a role as well.

(PPAR-y ligands) for diabetes, sebum are preputial cells serve as a model for human sebocytes in the laboratory. 25 In rat preputial cells, agonists of the PPAR-y receptor, such as drugs of the thiazolidinedione class, increase lipid

It has long been recognized that sebaceous glands require androgenic stimulation to produce significant quantities of sebum. Individuals with a genetic deficiency of androgen receptors (complete androgen insensitivity) have no detectable sebum secretion and do not develop acne. 14 However, there is still a question as to which androgen is physi

Androge ns

undifferentiated, sebaceous lipids.

acteristic cytoplasmic accumulation of Isotretinoin does not interact with any of the known retinoid receptors. It may serve as a prodrug for the synthesis of all-trans retinoic acid or 9-cis retinoic acid, which do interact with retinoid

FGFR1 and FGFR2 are expressed in the epidermis Expression localized and of to skin appendages. and FGFR4 is vessels and FGFR3 dermal

Fibroblast Growth Factor Receptors

microvessels and is notably absent in epidermis and ap-