Physiology, Sebaceous Glands


Article Author:
Ezra Hoover


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Karthik Krishnamurthy


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Tehmina Warsi


Updated:
4/25/2019 1:31:12 AM

Introduction

The sebaceous gland (SG) is integral to the structure and function of the skin, providing 90% of its surface lipids. While much of the focus relating to the sebaceous gland comes from its central role in acne vulgaris, a number of new functions have been more recently elucidated that highlight this versatile cellular unit’s complex role in skin homeostasis. The SG is special in at least two ways. Firstly, the product of this gland is synthesized via holocrine secretion, a unique method characterized by the purposeful self-destruction of its primary cellular unit, the sebocyte. Secondly, despite being of epithelial origin and possessing numerous hormone receptors, sebocytes engage in lipid synthesis and metabolism, a job normally reserved for adipocytes. Thus, the SG can be considered both a hormonal target as well as an endocrine organ.[1][2][3]

Cellular

The SG can be grossly identified by its “foamy” appearance on microscopy. The cells appear round and empty because their plentiful lipid contents are washed away during the staining process. Relatively undifferentiated sebocytes are located along the outer layers of the gland, gradually becoming more differentiated and filled with lipid products toward the center. At the center, mature sebocytes undergo apoptosis, degrade, and form the necrosis zone, eventually releasing their contents that combine to form sebum. This process of lipid synthesis and discharge takes about one week in total.

Development

The SG is located in the mid-dermis and almost always develops alongside a hair follicle, with an outlet emptying into the follicular canal. This association is known in conjunction as the pilosebaceous unit. A small number of SGs known as Meibomian glands open directly onto the skin in the epithelium of the eyelid and help to enhance the lubricating properties of tears. 

The embryological development of the SG lies in the process of ingrowth of ectodermal cells into the mesoderm. By weeks 13 to 15 of fetal life, the SG can distinctly be visualized differentiating in a cephalocaudal sequence, in association with the hair follicle. At 17 weeks, lipid drops become visible at the center of the gland. The developing common excretory duct, which will serve as a focal point of attachment for the sebaceous gland acini, begins as a solid cord-like structure. The sebum-filled cells comprising the cord eventually rupture and form a channel that becomes the first pilosebaceous canal. The ductal opening of the SG into the hair follicle is an important anatomical boundary; between this opening and the arrector pili muscle lies the bulge region of the hair follicle, a vital source of local stem cells. Interestingly, sebum is demonstrably the first glandular product made by the body. The approximate number of SGs remains mostly constant throughout life, but their size tends to increase with age, especially during adolescence. 

Function

The SG contributes the vast majority of skin surface lipids via its main product sebum, which helps to seal in moisture and prevent desiccation of the skin. Because SGs empty into the hair canal, sebum mostly escapes onto the skin surface via a wicking action involving the hair shaft. In addition to cell debris and lipids, sebum also contains antimicrobial substances, free fatty acids, and matrix metalloproteinases. These elements, combined with the formation of a cutaneous lipid film, help protect the skin from external insults.[4][5]

The SG is also an important site for androgen processing and modulation. All of the enzymes necessary for the transformation of cholesterol to steroids or adrenal precursors, such as dehydroepiandrosterone, are found in the skin. The SG also can inactivate androgens via the presence of hydroxysteroid dehydrogenase, an enzyme present as early as 16 weeks of fetal life. The type-1 isoform of 5-alpha-reductase, which serves to convert testosterone into its most potent form, is also abundantly produced in the SG, especially SGs found on the face and scalp.

The SG is also importantly under hormonal control. Androgens regulate SG function through binding to nuclear androgen receptors (AR). ARs have been demonstrated in numerous components of the skin, with a particular predilection for the SG, where androgens stimulate cell proliferation and lipogenesis. 

Corticotropin-releasing hormone (CRH) stimulates local skin cell receptors via paracrine methods, leading to increased levels of proopiomelanocortin (POMC) and lowering IL-8 synthesis in sebocytes as well as inducing cortisol production. These effects together have a powerful anti-inflammatory effect that counteracts the normal stress-signal cascade and helps limit excessive tissue damage.

Clinical Significance

The most commonly discussed pathology relating to the SG is acne vulgaris. Some estimate that up to 80% of people will experience acne at some point during their lifetime, and 20% of those will exhibit severe forms involving painful cysts, sinus tract formation, and permanent scarring. The pathogenesis of acne is complex, with the SG playing a prominent role. During puberty, high levels of androgen production stimulate SGs to increased sebum production. This results in the formation of sebum plugs, which in combination with other factors results in the characteristic open (blackheads) and closed (whiteheads) comedones of acne. Many individuals present with a form of acne at birth. Acne neonatorum, which presents within the first four weeks of life, occurs in up to 20% of newborns. Additionally, childhood acne is strongly correlated with the development of persistent acne later in life.[6][7]

The SG commonly takes on an enlarged appearance as patients age. This benign condition is known as sebaceous hyperplasia. While these small lesions are a purely cosmetic annoyance; to the inexperienced practitioner, they can appear similar to basal cell carcinoma and prompt unnecessary biopsy.  However, SGs can occasionally give rise to tumors, at which point they are known as sebaceous adenomas. Muir-Torre Syndrome, a rare, autosomal dominant condition, is characterized by sebaceous neoplasms as well as visceral malignancies. The high potential for metastasis and death in this syndrome (up to 25% according to some studies) necessitates surgical removal of these lesions with a wide margin to reduce the risk of recurrence.[8]

Interestingly, the SG also seems to be linked to androgenetic alopecia or pattern baldness, a genetic disorder involving the gradual diminishment in size, quality, and number of scalp hairs. Histologic examination of affected areas demonstrates a marked increase in the size of the associated SG, suggesting that overgrowth of the gland and relative preservation of the follicular stem cells could be important factors in the etiology of this condition.


  • Image 6333 Not availableImage 6333 Not available
    Contributed by Sarah Ferrer-Bruker, DO.
Attributed To: Contributed by Sarah Ferrer-Bruker, DO.

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Physiology, Sebaceous Glands - Questions

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Sebaceous glands secrete their product via which method?



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Although the majority of sebaceous glands open into a hair follicle, some put out their products directly onto the epithelium. What is the term for this gland in the eyelid?



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When do fetal sebaceous glands first appear?



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Which of the following directly adjacent to the sebaceous gland's opening into the follicular canal?



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Which enzyme enables the sebaceous gland to play a role in hormonal modulation via local inactivation of androgens?



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Sebum plays a vital role in forming the protective lipid barrier of the skin. How does sebum find its way onto the skin?



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Physiology, Sebaceous Glands - References

References

Agarwal S,Krishnamurthy K, Histology, Skin 2019 Jan;     [PubMed]
Paniagua Gonzalez LM,Tschen JA,Cohen PR, Ectopic Sebaceous Glands in the Hair Follicle Matrix: Case Reports and Literature Review of this Embryogenic Anomaly. Cureus. 2018 Nov 17;     [PubMed]
Fulton EH,Kaley JR,Gardner JM, Skin Adnexal Tumors in Plain Language: A Practical Approach for the General Surgical Pathologist. Archives of pathology     [PubMed]
Weir CB,St.Hilaire NJ, Epidermal Inclusion Cyst 2019 Jan;     [PubMed]
Zaballos P,Gómez-Martín I,Martin JM,Bañuls J, Dermoscopy of Adnexal Tumors. Dermatologic clinics. 2018 Oct;     [PubMed]
Xu H,Li H, Acne, the Skin Microbiome, and Antibiotic Treatment. American journal of clinical dermatology. 2019 Jan 10;     [PubMed]
Schneider MR,Zouboulis CC, Primary sebocytes and sebaceous gland cell lines for studying sebaceous lipogenesis and sebaceous gland diseases. Experimental dermatology. 2018 May;     [PubMed]
Vidal CI,Sutton A,Armbrect EA,Lee JB,Litzner BR,Hurley MY,Alam M,Duncan LM,Elston DM,Emanuel PO,Ferringer T,Fung MA,Hosler GA,Lazar AJ,Lowe L,Plaza JA,Robinson JK,Schaffer A, Muir-Torre Syndrome Appropriate Use Criteria: Effect of Patient Age on Appropriate Use Scores. Journal of cutaneous pathology. 2019 Mar 20;     [PubMed]

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