Structure of the Pilosebaceous Gland

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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 levels of androgens at puberty do not induce gross ultrastructural changes (50).

In human skin, the cells of sebaceous glands, called sebocytes, which are modified keratinocytes, can be divided into three major cell types determined by structure: undifferentiated or dividing, differentiated, and mature. The undifferen-tiated cells are attached to the basement membrane by hemidesmosomes. These cells tend to be cuboidal and are characterized by the possession of large nuclei, numerous mitochondria, tonofilaments, small golgi bodies, a high free ribosome, and glycogen granule content. No sebum is apparent in these cells. A second pool of dividing cells has been described to occur near the insertion of the sebaceous duct. These cells have a higher labeling index with tritiated thymidine (19 — 24%) compared to the germinative cells at the periphery of the gland (8 — 10%), implying that these cells have a higher turnover rate. Langerhans cells, which participate in the immune function of skin, are also found among the undif-ferentiated layer.

The sebocytes differentiate centripetally, that is, toward the center of the lobule. They take on a rounded appearance and the volume of cytoplasm decreases as the cells become filled with lipid containing vacuoles. The cells develop an extensive golgi apparatus, smooth endoplasmic reticulum, numerous mitochondria, free ribosomes, and glycogen. As differentiation progresses, lysosomes become apparent, which are thought to originate from the golgi apparatus. These are enriched with acid phosphatase activity. The mature cells in the center of the gland, near the insertion of the sebaceous duct, are approximately 100 to 150 times larger in volume than the basal cells. At this point, cytoplasmic organelles and nuclei degenerate and the mature cells disintegrate to produce the oily liquid sebum, a so-called holocrine secretion.

In sebaceous glands, the release of sebum from the mature cells into the sebaceous duct is thought to be a consequence of physical displacement of mature cells by new cells from the basal layer. Acid esterases and phosphatases have been demonstrated histochemically in the central portion of sebaceous glands (51), where they may be involved in holocrine secretion (52).

It was generally accepted that sebaceous glands were not innervated (53) until a very specific silver staining procedure was used on sections of sebaceous glands. This showed that nerve fibers do, in fact, penetrate the connective tissue capsule of the gland and enter between the lobules, reaching the inner part of the sebaceous lobule (54). These fibers may play a role in the holocrine secretion of sebum or they may secrete neuropeptides into sebum before the sebum exits from the gland. Certainly in acne, there is evidence of increased innervation of the sebaceous gland with increased expression of nerve growth factor (NGF) (55).

SECTION TWO: SEBUM Sebum Production

Sebum is an oily liquid containing triglycerides, free fatty acids, wax esters, squa-lene, and a little cholesterol produced by the gland. It is modified by bacteria that hydrolyze triglycerides to produce free fatty acids, thus a sample of skin surface lipids has a different composition compared to sebum produced by the gland (Table 2).

The delay between sebum synthesis, as measured by the incorporation of injected 14-C acetate into forehead skin of four healthy male subjects, and the subsequent excretion of radiolabeled sebum was determined to be eight days (56). This was similar to the five days reported for the delay between the onset of fasting and initial change in composition of skin surface lipids reported by Pochi et al. in 1970 (57). However, the overall process from sebocyte cell division to cell rupture is longer, about 14 days (58). In the beard and scalp follicles, it is believed that the hairs act as a wick to facilitate the passage of sebum to the surface of the skin. In follicles, which possess a vellus hair, the sebum may pool and form a follicular reservoir (59). Thus, the rate of sebum excretion onto the skin surface is a function of the rate of sebocyte proliferation, lipid synthesis, cell lysis, and the rate of flow through the follicular reservoir.

Sebum secretion is increased around puberty under the influence of andro-gens, concomitant with sebaceous gland enlargement. In human males, sebum secretion continues until the age of 80, but in females it drops significantly in the decade after menopause (60). In elderly individuals, sebaceous glands may undergo hyperplasia, but this does not seem to result in an increase in sebum output (61).

TABLE 2 Composition of Sebum

Sebum produced Sebum obtained from by gland (%) skin surface (%)

Triglycerides 60 40

Free fatty acids 40 20

Wax esters 25 25

Squalene 15 15

Cholesterol + cholesterol 1-2 1-2 esters

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