Embryologic, Histologic, and Anatomic Aspects
A sebaceous gland, a lipid-producing epithelial structure, develops in the fourth month of fetal life from a protuberance of epithelium that lies between the uppermost protrusion, which represents the future apocrine unit, and the lower bulge, which represents the site for future attachment of muscles of hair erection. With the exception of the palms, soles, and dorsa of the feet, sebaceous glands of various sizes are distributed over the entire skin surface. They are most populous and most productive on the scalp and face, and are largest on the forehead, nose, and upper part of the back. Nearly all sebaceous glands are connected by a duct to infundibular epidermis, the entry of the duct being at the junction of infundibulum and isthmus (Fig. 1.43). On some sites, e.g., the buccal mucosa and vermilion of the lip (Fordyce’s spots), areolae of women (Montgomery’s tubercles), labia minora and glans (Tyson’s glands), and eyelids (meibomian glands), sebaceous glands are joined to infundibula in the absence of follicles; no isthmus, stem, or bulb is present. Certain hair follicles, peculiarly those designated sebaceous follicles, are puny vellus ones overshadowed by large, multilobular sebaceous glands. “Sebaceous follicles” are found on the face, excluding the region of the beard, and on the upper part of the chest, back, and shoulders. When widely dilated ostia of infundibula affiliated with sebaceous follicles are plugged by corneocytes, the result is comedones, important lesions of acne vulgaris.
Schematic drawing of a sebaceous gland that, through a distinctive duct, enters the epidermofollicular unit at the junction of infundibulum and isthmus.
Sebaceous glands are well formed in neonates as a consequence largely of the effects of maternal androgens that crossed the placenta and stimulated the cells of the middle protuberance to proliferate and produce lipid. When the influence of maternal androgens no longer is operative, which is a matter of only a few weeks, sebaceous glands in an infant begin to shrink and nearly disappear. The residua of the sebaceous lobules are undifferentiated cells disposed in cords that hang like a cloak, or mantle, along the sides of both vellus and terminal follicles (Fig. 1.44). A mantle is continuous with an infundibulofollicular structure, originating at the junction of an infundibulum and isthmus and descending for a short distance parallel to the follicle. What in sections of tissue oriented vertically looks like a cloak composed of cords of undifferentiated cells is seen in sections oriented horizontally to be a skirt that encircles the follicle. At puberty, in response to endogenous androgens, those undifferentiated epithelial cells proliferate once again and, one by one, accumulate lipid. In the course of weeks, fully lipidized sebaceous lobules, as well as ducts, come to replace undifferentiated cells of the mantle. After scores of years, at menopause and andropause when the effects of androgens wane, the sebaceous lobules begin to involute and their residua are mantles once again. In a random section from normal skin of a face, particularly of an eyelid of a middle-aged or older person, sebaceous units may be seen in various stages, ranging from fully formed sebaceous lobules to undifferentiated mantles (Fig. 1.45). From these observations, it may be inferred that sebaceous units, like hair follicles, are engaged in a cycle, but the cycles of follicles and sebaceous glands are wholly independent of one another; the cycle of a sebaceous gland occurs only twice in a lifetime (Fig. 1.46), in contrast to that of a follicle, which occurs at intervals of weeks, months, or years, depending on anatomic site and, on certain sites, effects of androgens, throughout a lifetime.
Schematic representation of the mantle of a follicle. Although in cross section a mantle, which emanates from the junction of infundibulum and isthmus, vaguely resembles a cloak, in three dimensions it is seen to envelop the upper part of the follicle in the manner of a skirt. Prior to puberty, the mantle consists of undifferentiated cells that with the flow of androgens at puberty mature into fully formed sebaceous units, the ducts of which enter the base of the infundibulum at several loci along the circumference of a follicle.
Mantles pictured at low (A) and high (B) magnification. Mantles are cords of undifferentiated epithelial cells that emanate from the junction of infundibulum and isthmus and, in vertical section, appear to hang like cloaks along the sides of the upper part of follicles. At puberty, the cells of the mantle proliferate, become progressively vacuolated, and eventuate in fully mature sebaceous glands and ducts. After several decades, sebaceous lobules involute, completion of the process being signified by formation, again, of mantles, such as those pictured here in a section from the face of an older person. (From AB Ackerman, H Jacubovic. In: Moschella SL, Hurley HJ, eds. Dermatology, 3rd ed. Philadelphia: W.B. Saunders, 1992.)
The cycle of a sebaceous gland is unrelated completely to the cycle of a follicle. The horseshoe-shaped cords of epithelial cells are mantles that represent anlagen of sebaceous glands early in life and residua of them later in life.
A sebaceous gland has a distinctive appearance as viewed by conventional microscopy, the result of epithelial cells that grow in a centripetal manner to become lobules and produce lipid (Fig. 1.47). An individual sebaceous lobule consists of an outer row of undifferentiated, somewhat flat immature cells that possess a large nucleus and homogeneous pale basophilic cytoplasm. Those generative cells are analogous to cells in the basal layer of the epidermis. As the cells at the periphery of sebaceous lobules mature, lipids accumulate and eventually fill the cytoplasm. Enlarged mature cells in the center of a sebaceous lobule have pale-staining foamy cytoplasm and a nucleus that is scalloped, owing to compression of it by droplets of lipid. As the vacuolated cells become displaced ever closer to the sebaceous duct, they gradually disintegrate into an amorphous mass of lipid and cellular debris known, in conglomerate, as sebaceous secretion. After discharge of that secretion into a duct and during its passage through the infundibulum to the skin surface, it carries with it normal flora of bacteria, yeasts, and mites, as well as desquamated corneocytes, i.e., a mixture of elements that on the surface of the skin is known as “sebum.”
Nuclei of cells nearest to the peripheral generative layer of a sebaceous lobule are round, but become scalloped as they differentiate owing to compression of them by droplets of lipid. The cells at the periphery of a lobule are immature ones, those internal to them being progressively more mature. (x306)
The duct of a sebaceous gland marks the site where lipid-producing glandular cells of sebaceous lobules meet stratified squamous epithelium of an infundibulum. A sebaceous duct is lined by a thin cornifying squamous epithelium with a barely detectable granular zone that becomes more noticeable as the wall of the duct widens in its course from sebaceous gland toward infundibulum. The cornified layer of a sebaceous duct is thin, its corneocytes are arranged compactly, and its luminal border is marked by distinctive crenulations.
The several lobules that make up a sebaceous gland are surrounded by a basement membrane that is periodic acid-Schiff-positive, and by a thin, highly vascular zone of periadnexal connective tissue. Sebaceous glands are not innervated by motor nerves.
The mite, Demodex folliculorum, is present commonly not only within infundibula, but also within sebaceous ducts of infundibuloapocrine-sebaceous-follicular units positioned on the face. That organism is a normal inhabitant of those sites.
Study of sebaceous glands by electron microscopy (Fig. 1.48) reinforces observations made by conventional microscopy. The peripheral immature generative cells contain little lipid in their cytoplasm but do house numerous tonofilaments, prominent rough and smooth endoplasmic reticulum, Golgi apparatus, particles of glycogen, and many mitochondria. As differentiation proceeds, glycogen is consumed, tonofilaments are displaced, and the cytoplasm fills with lipid-containing vacuoles that arise from abundant smooth endoplasmic reticulum in the region of the Golgi apparatus. As cells mature, lipid-laden vacuoles enlarge progressively and fuse with one another. Eventually, membranes of remarkably swollen mature cells rupture and release into a sebaceous duct lipid, remnants of a nucleus, and cytoplasmic organelles.
Sebocyte filled with lipid. (x14,500) (Courtesy of Ken Hashimoto, M.D.)
The sebaceous gland is considered to be holocrine (G. holo “whole”) in type because, in the process of producing sebaceous secretion, the entire sebaceous cell and its contents are cast off into a sebaceous duct.
Sebaceous secretion contains a complex mixture of lipids. The major components, in descending order of magnitude, are triglycerides, wax esters, squalene, cholesterol esters, and cholesterol. Free fatty acids that come into being during the breakdown of triglycerides by lipases secreted by bacteria, e.g., Propionibacterium acnes and Propionibacterium granulosum, are present in sebum and are thought to be important in the pathogenesis of the suppurative infundibulitis of acne vulgaris.
Although sebaceous glands are apparent readily in sections of tissue of newborn skin, they regress soon afterwards and remain small throughout childhood. If, before age 8, sebaceous glands enlarge and become increasingly productive, it may be inferred that puberty has arrived early; a cause for that should be sought. Maturation of sebaceous glands continues throughout adolescence and remains relatively unchanged until many years later, decreasing after menopause in women and after andropause in men. The quantity of sebum diminishes as aging advances, but, curiously, sebaceous glands do not become noticeably smaller as the turnover of mature sebocytes decreases.
In conclusion, the amount and rate of sebaceous secretion are governed by the action of androgens on immature sebocytes. Sebum is not known to have any role physiologic in humans.