2 - 6 - SKIN GLANDS: SEBACEOUS, ECCRINE AND APOCRINE GLANDS Flashcards
(30 cards)
multilobular structures of epithelial origin that consist of acini connected to a common excretory duct, the sebaceous duct (ductus seboglandularis) (Fig. 6-1)
Figure 6-1 Cross-section of a pilosebaceous unit: a multiacinar sebaceous gkland associated with a hair follicle (HF). AP, arrector pili muscle (×20); SD, sebaceous duct, Sebum, sebum and keratin. (Modified with permission from: Zouboulis CC, Tsatsou F. Anatomy of the sebaceous gland. In: Zouboulis CC, Katsambas AD, Kligman AM, eds. Pathogenesis and Treatment of Acne and Rosacea. Berlin: Springer; 2014:27-31. Copyright © 2014.)
Human sebaceous glands
Sebaceous glands are composed of sebocytes, which are lipid-producing uniquely differentiated epithelial cells. 1,2 On the other hand, the sebaceous duct is lined by undifferentiated keratinocytes and is usually associated with a hair follicle which is composed of stratified squamous epithelium. The periphery of the sebaceous gland is a basal cell layer composed of small, cuboidal, nucleated, highly mitotic sebocytes. 1,3 Cells progress toward the middle of the gland and accumulate lipid droplets (LDs) as they transform into terminally differentiated cells, full of lipids.
The latter lack all other cellular organelles, burst, and die, excreting their entire contents to the duct in a holocrine manner (Fig. 6-2). Surrounding the glands are connective tissue capsules composed of collagen fibers that provide physical support.
Figure 6-2 A, Hematoxylin and eosin–stained section of the human sebaceous gland showing the different stages of sebocyte differentiation. Cells progress toward the middle of the gland, lose their nuclei, and organelles, and accumulate lipid droplets. B, Differentiation stages of human sebocytes in tissue (left) 19 and in vitro (right) 3 according to Tosti17 and McEwan Jenkinson and coworkers. 18 Undifferentiated sebocytes are small cells with a high nucleocytoplasmic ratio. Early differentiated sebocytes are larger cells with a decreased nucleocyloplasmic ratio compared with the undifferentiated sebocytes and a few lipid droplets arranged in the perinuclear area. Advanced differentiated sebocytes are cells with further increases in size and decreases of the nucleocytoplasmic ratio. Multiple cytoplasmic lipid droplets are distributed inside the cytoplasm. Fully differentiated sebocytes are cells with abundant, partially large, cytoplasmic lipid droplets. Mature sebocytes are disorganized large cell with denatured nucelei; the lack of cytoplasmic lipids is caused by lysis of the cell blood cell membrane.
Sebaceous glands are associated with hair follicles all over the body. A sebaceous gland associated with a hair follicle is termed ______
pilosebaceous unit
The glands may also be found in certain nonhairy sites, including the eyelids (Meibomian glands, tarsal glands), the nipples (Montgomery glands, areolar glands), around the genitals (Tyson glands), and the mucosa (lips, gums and inner cheeks, and genitals; Fordyce spots).
Fordyce spots open and release their content directly to the epithelial surface. The latter are visible to the unaided eye because of their large size (up to 2 to 3 mm) and the transparency of the oral epithelium (Fig. 6-3).
Figure 6-3 Fordyce spots at the upper lip mucosa.
Areas devoid of sebaceous glands
Only the palms and soles, which have no hair follicles, are totally devoid of sebaceous glands.
In addition, the dorsal surfaces of the hand and foot have sparse sebaceous glands. 5 Sebaceous glands vary considerably in size, even within the same individual and within the same anatomic area. On the external body surface, most glands are only a fraction of a millimeter in size. The largest glands and greatest density of glands are located on the nose (1600 glands/cm2 ) followed by the face and scalp (up to 400 to 900 glands/cm2 ). 4 The hairs associated with these large glands are often tiny, and the total structure is more specifically termed sebaceous follicles, being a pilosebaceous unit variant, the other two being the terminal hair follicle and the vellus hair follicle.
The sebaceous glands exude lipids by disintegration of entire cells, a process known as ___________
HOLOCRINE SECRETION
Holocrine secretion by sebaceous gland cells does not occur mechanically via increased cell volume, as considered previously, but rather from a multistep, cell-specific lysosomal DNase2-mediated mode of programmed cell death, which differs from apoptosis, necroptosis, and cornification.22
As sebaceous gland cells are displaced into the center of the gland, they begin to produce lipids, which accumulate in droplets. With approaching the sebaceous duct, they disintegrate and release their content. Only neutral lipids reach the skin surface. Proteins, nucleic acids, and the membrane phospholipids are digested and are apparently recycled during the disintegration of the cells. 2 Sebaceous gland secretion can be enhanced with increased rates of induced terminal sebocyte differentiation.
LIPID COMPOSITION OF SEBUM
Figure 6-6 Human sebaceous gland lipids. The structures of the cholesterol ester, wax ester, and triglyceride are representative of the many species that are present. Two sebaceous-type unsaturated fatty acid moieties are shown: sapienic acid (16:1∆6) (in the wax ester structure) and sebaleic acid (18:2∆5,8) (in the triglyceride structure). Anteiso branching is shown in the alcohol moiety of the wax ester, and iso branching is shown in the triglyceride.
Sebum production is a continuous event. The exact mechanisms underlying its regulation are not fully defined. Complexity and uniqueness are the two terms that best characterize sebaceous lipids. ∆6 desaturation, wax ester synthesis, and squalene accumulation are examples that manifest sebaceous lipid biology.22-24 Genetic knockout animal models of lipid synthesis demonstrate dramatic changes in skin physiology and pathology, resulting from impairment of sebaceous lipid pathways. 25 Human sebum, as it leaves the sebaceous gland, contains a mixture of nonpolar (neutral) lipids, mainly triglycerides, wax esters, squalene, and smaller amounts of cholesterol and cholesterol esters (Fig. 6-6). During passage of sebum through the hair canal, bacterial enzymes hydrolyze some of the triglycerides, so that the lipid mixture reaching the skin surface contains free fatty acids and small proportions of mono- and diglycerides, in addition to the original components. Triglycerides, diglycerides, and free fatty acids form 40% to 60% of total skin surface lipids followed by wax esters (25% to 30%), squalene (12% to 15%), cholesterol esters (3% to 6%), and cholesterol (1.5% to 2.5%). 26,27 The wax esters and squalene distinguish sebum from the lipids of human internal organs, which contain no wax esters and little squalene. However, human sebaceous glands appear to be unable to transform squalene to sterols, such as cholesterol. The patterns of unsaturation of the fatty acids in the triglycerides, wax esters, and cholesterol esters also distinguish human sebum from the lipids of other organs. The “normal” mammalian pathway of desaturation involves inserting a double bond between the 9th and 10th carbons of stearic acid (18:0) to form oleic acid (18:1∆9). However, in human sebaceous glands, the predominant pattern is the insertion of a ∆6 double bond into palmitic acid (16:0). The resulting sapienic acid (16:1∆6) (see Fig. 6-6) is the major fatty acid of adult human sebum. Elongation of the chain by two carbons and insertion of another double bond gives sebaleic acid (18:2∆5,8), a fatty acid thought to be unique to human sebum.22-24
Sebaceous fatty acids and alcohols are also distinguished by chain branching. Methyl branches can occur on the penultimate carbon of a fatty acid chain (iso branching), on the third from the last (antepenultimate) carbon (anteiso branching), or on any even-numbered carbon (internal branching). Examples of these unusual unsaturated and branchedchain moieties are included in the lipid structures in Fig. 6-6.
most potent pharmacologic inhibitor of sebum secretion
Isotretinoin (13-cis-retinoic acid, 13-cis-RA)
Significant reductions in sebum production can be observed as early as 2 weeks after use. 63,64 Histologically, sebaceous glands are markedly reduced in size, and individual sebocytes appear undifferentiated lacking the characteristic cytoplasmic accumulation of sebaceous lipids.3,65
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, which interacts with retinoid receptors expressed in sebaceous gland cells (retinoic acid receptors [RARs; isotypes α and γ] and retinoid X receptors [RXRs; isotypes α, β, γ]). 66 However, it has greater sebosuppressive action than do all-trans- or 9-cis-retinoic acid. 67 13-cis-RA exerts pluripotent effects on human sebaceous gland cells and their lipogenesis.63 Inhibition of androgen synthesis, cell cycle arrest, and apoptosis by 13-cis-RA may explain the reduction of sebaceous gland size after treatment.
members of the nuclear hormone receptor family and act as transcriptional regulators of a variety of genes, including those involved in lipid metabolism in adipose tissue, liver, and skin
PEROXISOMEPROLIFERATOR ACTIVATED RECEPTORS
PPARs are similar to retinoid receptors in many ways. Each of these receptors forms heterodimers with retinoid X receptors to regulate the transcription of genes involved in a variety of processes, including lipid metabolism and cellular proliferation and differentiation. PPARα, δ, and γ receptor subtypes have been detected in basal sebaceous gland cells. 54 PPARγ is also detected within differentiated cells. Pharmacologic PPAR-γ modulation regulates sebogenesis and inflammation in SZ95
human sebaceous gland cells. 68 In patients receiving fibrates (PPAR-α ligands) for hyperlipidemia or thiazolidinediones (PPAR-γ ligands) for diabetes, sebum secretion rates are increased.69
PPAR-γ–RXR-α and LXR–RXRα promoter interactions are of crucial importance for the regulation of key genes of lipid metabolism. Although various fatty acids, eicosanoids, and prostanoids activate PPARs, oxysterols and intermediate products of the cholesterol biosynthetic pathway activate LXRs. PPAR-α agonists and PPAR-γ antagonists may reduce sebaceous lipid synthesis and as such may be useful in the treatment of acne. On the other hand, whereas PPAR-γ agonists may be beneficial in aging skin, PPAR-δ agonists may be involved in sebaceous tumorigenesis.
members of the NHR family, play a critical role in cholesterol homeostasis and lipid metabolism.
LXR
Treatment of SZ95 sebaceous gland cells with the LXR ligands TO901317 or 22(R)hydroxycholesterol enhanced accumulation of LDs in the cells, which could be explained through induction of the expression of the LXRα receptor and known LXR targets, such as fatty acid synthase and sterol regulatory element–binding protein-1 (SREBP-1).
How many sweat glands does a human have?
A human has 2 to 4 million sweat glands (200 to 400/cm 2 of skin surface).
How much sweat is produced by acclimatized individuals?
Up to 10 L/day of sweat is produced by acclimatized individuals.
In humans, sweat glands are generally classified into ______ and _____
apocrine and eccrine types
strongest stimulus for sweating
Hypothalamic temperature
major stimulus of eccrine sweat glands secreted by sympathetic nerves
Acetylcholine
controls apocrine gland secretion
Adrenergic stimulation
inhibits sweating by preventing acetylcholine release
Botulinum toxin
major source of eccrine gland adenosine triphosphate
Oxidative metabolism of glucose
Odiferous precursors secretion is controlled by
MRP8 encoded by ABCC11
■ Ductal reabsorption conserves NaCl.
■ Bacteria are necessary for apocrine odor.
marker of ductal cells of eccrine but not of apocrine sweat glands
stage-specific embryonic antigen-4 (SSEA-4)
Sweating induced by emotional stress (emotional sweating) can occur over the whole skin surface in some individuals, but it is usually confined to the
palms, soles, axillae, and forehead.
Emotional sweating
on the palms and soles ceases during sleep, but
thermal sweating occurs even during sleep if the body
temperature rises. Because both types of sweating can
be inhibited by atropine, emotional sweating is cholinergically
medicated.
- The earliest known signal necessary for sebaceous gland development.
- Essential for the specification of early hair follicle stem cells and therefore the morphogenesis of both structures
SOX9
What is establieshed near the entrance of the sebaceous gland and acts as a marker of terminal epithelial cell differentiation?
PRDM-1
Loss of this results in increased gene expression of c-myc which is an essential player in sebaceous gland homeostasis
PRDM-1
Hocrine secretion of sebaceous cells occurs through what multistep mechanism?
Cell-specific, lysosomal DNase2-mediated mode of programmed cell death
