Squalene Biosynthesis

Human sebum contains a high percentage of squalene, in contrast to the epidermal lipids, which contain a higher proportion of cholesterol. In the sebaceous glands, therefore, the cholesterol biosynthetic pathway appears to be partly arrested in the steps after the production of squalene. This may be due to low activity of squa-lene epoxidase, or other enzyme of cholesterol biosynthesis, or the availability of substrates. For example, a ready supply of acetate appears to direct lipogenesis...

Free Fatty Acids

Sebum contains numerous fatty acids and many are quite unique in structure, including a wide variety of straight, branched, saturated, and unsaturated fatty acids (77). In human sebum, about 27 of fatty acids chains are saturated, with the greatest proportion being unsaturated (68 ). The vast majority of these are monounsaturated (64 ) and about 4 are diunsaturated, with the remainder being composed of fatty acid chains longer than 22 carbons (78). Monounsaturated fatty acids of sebum have a...

Biochemical Changes in the Infundibulum During Comedogenesis

The process of comedogenesis is thought to be due to hyperproliferation of ductal keratinocytes, inadequate separation of the ductal corneocytes, or a combination of both factors, resulting in microcomedones. Hyperproliferation of basal keratino-cytes in acne has been demonstrated (180,181) and correlates with keratin 16 expression, a marker for hyperproliferation suprabasally (182). Aldana et al. (183) proposed a cycling of normal follicles through different levels of expression of Ki-67 (a...

Role Of Antimicrobial Peptides In Acne

The epidermis forms an effective barrier, however, the hair canal, the distal ORS of the hair follicle, and the pilosebaceous duct constitute major ports of entry for microbial invasion in humans and harbor a rich residential microflora such as P. acnes, Staphylococcus epidermidis, Demodex folliculorum, and Malassezia furfur. The distal ORS and the pilosebaceous duct are also characterized by many features of innate and adaptive immunological activity such as classical and nonclassical MHC...

Phototherapy and Laser Therapy of Acne

Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A. Light-based treatments for acne are not new. A tan has long been known to help teens with pimples, and it would not be surprising to find reports of acne phototherapy dating from the 1930s. In my youth, a local dermatologist was treating many of us with what must have been a cold quartz lamp along with various creams and oral antibiotics. He told me that he knew that the light was helpful, but could not...

Peroxisome Proliferatoractivated Receptor Target Genes

PPARs regulate gene expression by binding to specific PPRE in the promoter regions of target genes (64). PPREs have a core element called DR-1, in which PPAR-RXR heterodimers preferentially bind to. Since stimulation of peroxisomal fatty acid -oxidation is one of the key effects of peroxisome proliferators, genes encoding enzymes of this pathway represent prime candidate target genes of PPARs. The first gene described was acyl-CoA oxidase that is the rate-limiting and specificity-defining...

Disorders Affecting Pilosebaceous Unit Biology

Various disorders affect pilosebaceous units, although these diseases are rarely life threatening. Three types of skin cysts exist epidermoid cysts result from squamous metaplasia of a damaged sebaceous gland, while trichilemmal cysts and steatocys-toma are both genetically determined structural aberrations of the pilosebaceous duct. Accumulation of material in the follicular lumen results in distension of the follicle, leading to the formation of noninflamed lesions that are typical of acne,...

Structure of the Pilosebaceous Gland

All sebaceous glands are similar in structure. They consist of either a single lobule (acinus) or a collection of acini. The glands are separated from the dermis by a connective tissue capsule, consisting of fine collagen fibers, fibroblasts, and a capillary plexus. The ultrastructure of human sebaceous cells does not vary significantly from one skin site to another nor does the ultrastructure of sebocytes of prepubertal children differ significantly from that of adults, implying that increased...

Changes in the Pilosebaceous Unit in Acne

There is no doubt that sebum plays an important etiological role in acne (99,168170). Patients with acne secrete more sebum than unaffected individuals and sebo-suppressive treatments alleviate acne the greater the inhibition the more profound the clinical response. In addition to elevated sebum excretion, it is well-established that acne is associated histologically and clinically with hypercornification of the duct epithelium (7,38,171). Ductal hypercornification results initially in the...

Sebum Secretion and Acne

Dows Institute, University of Iowa, Iowa City, Iowa, U.S.A. Sebum is synthesized in sebaceous glands, which are part of the pilosebaceous units of the skin (1). Sebaceous glands are epidermal appendages found in all regions of the skin, except the palmar and plantar surfaces however, the greatest density of glands is found in the scalp and facial areas. As sebocytes move from the basal layer at the periphery of the gland toward the lumen, they synthesize neutral lipids, which accumulate as...

The Sebaceous Gland Is a Steroidogenic Tissue

The skin and sebaceous glands are capable of synthesizing cholesterol de novo from acetate (22-24). Although this cholesterol is utilized in cell membranes, in the formation of the epidermal barrier, and is secreted in sebum, its use as a substrate for steroid hormone synthesis had not been established until recently. In order for steroid synthesis to occur, cholesterol needs to be translocated from the outer to the inner mitochondrial membrane. This process is regulated by the steroidogenic...

Effects Of Retinoids

Hypovitaminosis has been related to the expression of acne (25), and so its addition to skin should alleviate the condition. All-trans-RA was the first retinoid used, but it was ineffectual on acne when used systemically. 13-cis-RA (isotretinoin), however, is an extremely effective oral anti-acne drug by causing marked sebosuppression (26). 13-cis-RA has been shown to inhibit significantly sebocyte proliferation, differentiation, and lipid synthesis in vivo. Despite its potent biological...

Androgen Metabolism Within the Skin

Acne may be mediated by serum androgens, locally produced androgens, or a combination of both. Insights have been gained regarding the local metabolism of androgens within sebaceous glands (9). Such insights may be of benefit in the design of new acne therapies. The skin and sebaceous gland are capable of producing and metabolizing androgens (9). DHEAS is the major adrenal androgen precursor. It circulates in the blood stream in relatively high levels compared with other hormones with the...

Acne

It affects up to 80 of young adults, in whom it can induce stress, depression, and anxiety, as determined by psychometric scoring (47,111,112). Acne is a disease of the infundibulum or pore of the human sebaceous pilosebaceous unit and of the gland itself. This unit develops at puberty, appears only at the site of acne lesions (the chest, back, and face), and seems to have no other function than to sometimes produce acne lesions. The earlier forms of acne are...

The Molecular Biology of Retinoids and Their Receptors

Pml Rar Alfa Acido Retinoico

AVR Consulting Ltd., Northwich, Cheshire, U.K. Acne vulgaris is a multifactorial disease of the skin in areas rich in sebaceous follicles. It is characterized by seborrhea, hypercornification of the infundibulum (the neck of the sebaceous gland), and the presence of comedones and inflammatory lesions such as papules and pustules. The inflammatory pathway is mediated by antigenic and inflammatory products of Propionibacterium acnes (1). Although acne is mostly associated with puberty, persistent...

Oral Contraceptives Studied In Acne

Many oral contraceptives have been studied in the treatment of acne (Table 3). These include those containing ethinyl estradiol in combination with cyproter-one acetate (Diane, Dianette), ethynodiol diacetate (Demulen), levonorgestrel (TriPhasil, Alesse), norgestimate (Ortho Tri-Cyclen ), desogesterel (Desogen), and drosperinone (Yasmin, Yaz). Numerous studies point to the efficacy of ethinyl estradiol cyproterone acetate oral contraceptives (Diane and Dianette) in the treatment of acne....

Proposed Hybrid Method

The biggest obstacle to accurate measurement of sebum secretion rates is the need to deplete the sebaceous follicles. This can be overcome by 12 to 14 hours of adsorption onto bentonite prior to measurement. Once the reservoir is depleted, the Sebutape method is appealing for the actual sebum secretion measurement. The collection time could be shortened to one hour, and a digitized image of the Sebu-tape on its black backing should be captured immediately. Subsequently, this image can be...

Thyroid Hormones

Thyroid hormones exert an effect on sebum secretion since thyroidectomy decreases the rate of sebum secretion in rats and administration of thyroxine reverses this effect (140). Increases in sebum secretion rate were observed when thyroxine was given to hypothyroid patients (141), and immunohistochem-ical localization of thyroid hormone nuclear receptors has been demonstrated in human scalp follicles in the nuclei of the outer root sheath cells, dermal papilla cells, sheath cells, and sebaceous...

Structure of the Pilosebaceous Duct

Cornification Pilosebaceous Duct

The pilosebaceous duct is lined by a stratified, squamous epithelium consisting of keratinocytes. The duct lumen is frequently colonized by bacteria that rely on the keratinocytes and sebum as a source of nutrients. Several distinct anatomical parts of the duct can be recognized. The opening of the duct onto the surface of the skin is the orifice or ostium. The sebaceous follicles on the back frequently group together and emerge through one orifice (25), while those on the face and chest show...

Retinoid Types

The first developed topical retinoid was retinoic acid, or tretinoin. Tretinoin's flexible molecular structure allows it to bind all RAR and RXR subtypes, whereas tazar-otene and adapalene are more rigid, and therefore demonstrate receptor specificity (13). Tretinoin also has the capacity to bind cytosolic retinoid-activating binding proteins (CRABPs) that exist in two forms, I and II, and act as buffers for retinoic acid by controlling free intracellular concentration (3,10,11). Retinoid...

Overview of the Pathogenesis of Acne

Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A. Acne is an extremely complex disease with elements of pathogenesis involving defects in epidermal keratinization, androgen secretion, sebaceous function, bacterial growth, inflammation, and immunity. In the past 30 years, much has been worked out, and we now have a fairly detailed understanding of the events that result in an acne pimple, although there is also much left to be discovered. The initial...

Cytokines

Expression of IL-1a and b was demonstrated in sebaceous glands by immunohis-tochemistry (162), and mRNA for IL-1a was detected in cultured sebocytes (163). No change in staining pattern was observed when sebum was extracted from the samples, indicating that IL-1 is not associated with sebum. The function of IL-1 in normal sebaceous glands is unclear, although in vitro IL-1a and tumor necrosis factor a, inhibited sebaceous lipogenesis in sebaceous gland organ culture and induced...

Cell Biology of the Pilosebaceous Unit

Follicular Duct

Department of Research and Development, Nu Skin Enterprises, Provo, Utah, U.S.A. This chapter reviews the structure and function of the pilosebaceous unit and the controlling influences on the pilosebaceous unit and sebum secretion. The chapter is divided into three sections. Section I gives an account of the structure and function of the normal pilosebaceous unit Section II describes the biochemistry and regulation of pilosebaceous unit biology and finally, Section III deals briefly with the...

Mechanism Of Action

Topical retinoids act to clear and prevent the formation of the microcomedo, the precursor to acneiform lesions. The microcomedo is formed from the occlusion of the follicular ostium by the androgen-induced production of sebum and the accumulation of stratum corneum cells (5). In normal skin, the corneocytes of the hair follicle's infrainfundibular region are small and form a noncontinuous, incoherent layer of cells that easily desquamate individually into the follicular canal (1,2,6). They...

Regulation of Pilosebaceous Unit Activity

There are many controlling influences on the pilosebaceous unit (Fig. 3). The development of model systems for the sebaceous gland and duct has made it easier to study these pathways in vitro. Perhaps the most profound and well-known effect of hormones on the pilosebaceous unit is the one caused by androgens, more specifically in causing sebaceous gland enlargement, sebocyte proliferation, and lipid metabolism (91,92). It is well established that the increase in lipid production and enlargement...

Function of Sebum

In animals, sebum may provide odor it contains pheromones and may also condition the hair. However, in humans, the function of sebum is unclear (5) and it has been speculated that the sebaceous glands are vestigial (20). There is now an increasing body of evidence indicating that the sebaceous gland and the components of sebum play a crucial role in the homeostasis of skin (6). Sebum transports vitamin E, a lipophilic antioxidant, to the skin surface where it may play a key role in protecting...