Sebum and sebaceous glands

Definition and function

What is sebum? Sebum is a viscous fluid, chemically complex oil, intrinsic product of the skin sebaceous glands, SGs, that eventually excreted onto the surface of the skin, seemingly lubricates the stratum corneum and coats hair. Sebum secretion is species specific, hormonally controlled, genetically influenced and limitation of supply of fatty acids precursors. Sebaceous glands, located in the dermis, open up in infundibulum of a hair follicle, give rise to the acid mantle with a pH in the range of 4.5-6 except for certain areas, known as physiological holes of the acid mantle, comprised of interdigital region, the axilla and anogenital area, where higher pH is maintained . The acid mantle works to combat pathogens, viruses, bacteria, which generally are of alkaline pH. Sebum functions in skin moisture retention, thermoregulation as well as sun protection. This barrier also imparts distinctive function in immunology and microbiology of the skin by regulating inflammatory markers and modulation of the skin microbiome and indeed sebocytes recognition as immunomodulatory and immunocompetent cells is burgeoning through their contribution to production or regulation of cytokines, chemokines, adipokines such as leptin and lipid mediators. Sebum secretion declines persistently throughout the adult age, shown by Jacobsen measuring sebum wax esters.

Sebaceous follicle

Sebaceous follicle, composed of a hair follicle and sebaceous gland which releases sebum through follicular canal onto the skin

Over the past decade a growing cognizance of sebaceous glands, deeply constitutional to pathophysiology of the skin, delivers a broader and more integrated views of the function of the integument. Sebaceous glands’ sebum secretion is on a holocrine platform, built upon disintegration of sebocytes where their lipids synthesis into the droplets occurs. The sebocytes are destined to differentiation thereby they burst and release their fat content and cell debris into the hair follicle. These epithelial glands reside in the dermis, lined with sebocytes, equipped with hormonal receptors and embody skin’s androgen homeostasis, a virtue by which they are properly regarded as an endocrine organ. Sebaceous glands almost always are found associated with hair follicles where these glands secretions end up to with some exceptions such as meibomian glands in eyelids which, without intervention, deliver their content to the surface of the epithelium.

Sebum ought to be differentiated from skin surface lipids, and the two nomenclatures may not interchangeably be used since skin surface lipids are derived from two major sources, sebaceous glands which produces sebum and makes up to 90% of skin surface lipids, and epidermal keratinocytes which give rise to epidermal, stratum corneum, lipids with equal amounts of ceramides, cholesterol and fatty acids. Distribution of sebaceous glands in different areas of the skin contribute to different composition of skin lipids in various areas. Rich areas of sebaceous glands such as forehead have a surface lipid composition very similar to sebum.

Its production varies with age with an onset at puberty and a nadir after menopause in women or after sixth decade in men. Sebaceous glands differentiation and proliferation is hormonally-controlled and androgen-dependent via binding to androgen nuclear receptors as all enzyme for androgen production and modulation are available in the skin, with 5-alpha-dihydrotestosterone (5α-DHT), the principal player. Men’s skin in general generates more secretions, which could be explained by higher level of androgens. Corticotropin releasing hormone, CRH, is another hormone found in the skin which regulates sebocytes’ function by tempering synthesis of IL-8 in these cells. Several factors, hormones, nuclear receptors, have been gaining traction for their implication in maturation and differentiation of sebocytes, with insulin as most prominent one. Insulin promote lipid droplet accumulation and further maturation to bursting while epidermal growth factor, EGF, retionoids and vitamin D3 negatively impact it. SREBPs, sterol regulatory binding proteins, are a family of transcription factors recognized as key elements involved in lipid homeostasis within sebaceous glands, upregulated by liver X receptors, LXRs. SREBP-1c promotes activation of several lipogenic enzymes, namley, stearoly-C0A and Δ-6 desaturase, giving rise to increased proportion of monounsaturated fatty acids in sebum triglycerides such as sapienic acid. Vitmain A is known to be essential for sebocyte viability and differentiation albeit their proliferation is mainly affected by retinoids.

Central to the sebaceous glands function is what has been recognized as the secretome, growth factors, hormones, cytokines secreted by SGs before cell disruption, which despite making key contributions to immunemodulation of pilosebaceous milieu even under physiological status are not as yet well studied. One research on SZ95 sebocytes to determine major proteins associated with the secretome found IGF-binding protein 3, IGFBP3, as most abundant protein with regulatory function on IGF bioavailability, a principal modifier of the skin lipogenesis. Epidmeral growth factor, EGF, has been found to induce immune-related genes in sebocytes and bestow upon them a bioactivity they do not possess in its absence. EGF also activates IL-1 signaling which nurtures inflammation, keratinocytes proliferation and their aberrated differentiation, giving rise to comedogenesis.

Sebum lipid content

Sebum composition, Glycerides, Free fatty acids (FFA), Wax esters (WE), Squalene (SQ), Cholesterol esters (CE), Cholesterol (CH)

Composition

Sebum contains bioactive molecules whose function is not merely to serve as humectants but labor to protect against environmental extremes by their commitment to UV protection or antimicrobial activity as sebum-rich areas of the skin presents distinct immunology from sebum-deficient segmentaries. Following differentiation and apoptosis of sebocytes, sebum is formed in sebaceous glands by decomposition of lipid-containing cells, sebocytes, so cell debris, disintegrated mature sebocytes, as well as matrix metaloproteinases, MMP, can be found in its lipids. Three major lipid classes in human variant are triglycerides and free fatty acids, FFA (58%), wax esters, WE, (26%) and squalene , SQ(12%). Importantly, synthesis of SQ and WE is characteristic of sebaceous gland activity and is found no where else in the body even in epidermal surface lipids excreted from keratinocytes. Moreover, branched chain fatty acids and lipids with specific pattern of unsaturation are also exclusive to the sebum. Highly specific and concentrated in sebum, squalene is an unsaturated hydrocarbon and withal a precursor of cholesterol in most human tissues, where this conversion occurs. The triglycerides and FFA make up less than 60 percent of sebaceous glands products while their presence in skin surface lipids reaches to about 40 percent.

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