Everything you need to know about the physiology and function of sebaceous glands.

The sebaceous glands are specialised exocrine structures of the skin.

Sebaceous glands belong to the pilosebaceous apparatus, forming with the hair follicle and the arrector pili muscle a functional unit called the pilosebaceous unit. They are situated in the deep dermis and adopt a lobular shape, clustered around an excretory duct that opens into the hair follicle. This duct enables the sebum synthesised by the sebaceous glands at the base of the hair to ascend readily to the skin surface.

Note : There are also free sebaceous glands that are not associated with a hair, but these are in the minority.

Sebaceous glands are primarily composed of specialised sebaceous cells, derived from the proliferation of keratinocytes in the outer root sheath of the hair follicle. These cells, known as sebocytes, undergo a differentiation process culminating in programmed cell death. During this maturation, they synthesise a complex mixture of lipids that is subsequently released into the excretory canal: the sebum. Comprising approximately 50% triglycerides, 20% wax esters, 15% squalene, as well as small quantities of cholesterol and its esters and vitamin E, which imparts protective and moisturising properties.

The density and size of sebaceous glands vary significantly across different body sites. They are found abundantly on the face, especially on the forehead, nose and chin, corresponding to the famous zone T, but also on the scalp, chest and back, regions renowned for their high sebaceous secretion. Sebaceous glands are, however, absent from the palms of the hands and the soles of the feet.

Sebum production by the sebaceous glands is based on a specific physiological process known as holocrine secretion. This process is distinguished by the fact that sebum release does not simply occur by exocytosis, but by the complete destruction of the cells that produced it. At the periphery of the sebaceous gland are immature sebaceous cells corresponding to undifferentiated sebocytes. They exhibit a flattened shape and are in an active proliferation phase. Gradually, these cells migrate towards the centre of the gland, entering a maturation phase. During this stage, they become engorged with lipid droplets arising from the intracellular synthesis of various fatty compounds that will subsequently be found in the sebum.

As they undergo this internal migration, the sebocytes increase in volume and their lipid content becomes increasingly dense. When they reach the central zone, near the excretory duct, the sebocytes arrive at the end of their life cycle: their cell membrane weakens and then ruptures, fully releasing their lipid content. Once released, the sebum travels along the pilosebaceous duct to reach the skin’s surface. It then deposits both on the hair shaft and on the stratum corneum, where it mixes with epidermal lipids and sweat. This complex mixture will later form the hydrolipid film.

This ongoing renewal mechanism enables the sebaceous glands to produce a continuous natural lipid barrier that protects and hydrates the skin.

The activity of the sebaceous glands is regulated by a complex network of hormonal signals, growth factors and neuropeptide interactions. Androgens are central to this regulation, starting with 5α-dihydrotestosterone (5α-DHT), produced from testosterone by the type I 5α-reductase isoenzyme. Endowed with a high affinity for the androgen receptor in the sebaceous glands, 5α-DHT activates this receptor and promotes sebocyte proliferation. Conversely, oestrogens exert an inhibitory effect on sebaceous gland activity and on sebum synthesis, acting as a counterbalance to androgenic effects.

Alongside sex hormones, certain growth factors influence sebaceous physiology. Growth hormone (GH) and IGF-I (insulin-like growth factor I) are particularly involved, as evidenced by the rise in sebum secretion observed during adolescence, when GH and IGF-I reach their maximum plasma concentrations. IGF-I directly stimulates lipogenesis in sebocytes by activating the transcription factor SREBP-1, a regulator of the genes involved in fatty acid synthesis. This activation proceeds via the PI3K/Akt and MAPK/ERK signalling pathways. Correlations have been established between IGF-I levels and acne severity, as well as with plasma concentrations of 5α-DHT and DHEAS, emphasising the interconnection between lipid metabolism, androgens and IGF-I signalling.

Another notable player is fibroblast growth factor receptor 2b (FGFR-2b), whose expression is modulated by androgens and which contributes to keratinocyte proliferation. In certain pathologies, such as the acneiform nevus—a malformation characterised by epidermal hyperplasia—activating mutations in FGFR-2b result in sebaceous hyperactivity and alteration of the pilosebaceous unit. Experimental models have shown that postnatal ablation of FGFR-2b leads to complete atrophy of the sebaceous glands, confirming its structural role.

The regulation of sebaceous glands is not limited to hormones and growth factors. MicroRNAs, small non-coding sequences of around 21 nucleotides, provide an additional level of control by modulating gene expression after transcription. Certain microRNAs, such as miR-574-3p targeting the nuclear receptor RXRα, can significantly increase lipid synthesis when overexpressed. Others, involved in tumoural conditions of the sebaceous glands, influence the NF-κB, PTEN and TGF-β pathways, thereby affecting cell proliferation and cellular transformation.

Finally, although the sebaceous gland is richly vascularised to meet its high demands for nutrients and lipid precursors, its innervation remains less well defined. Neural networks surround the hair follicle and pass in close proximity to the gland, but the direct penetration of nerve fibres into it is still debated. However, the presence of receptors for various neuropeptides, such as CRH (corticotropin-releasing hormone), α-MSH and β-endorphin, suggests a heightened sensitivity to neuroendocrine signals. For example, CRH released in a circadian manner by the hypothalamus modulates the secretion of ACTH and POMC-derived peptides, which can directly influence sebaceous gland proliferation and differentiation.

The physiology of sebaceous glands thus depends on a dynamic equilibrium between hormonal signals, growth factors, post-transcriptional regulation and neuropeptide responses, each contributing to the fine-tuning of cell proliferation and sebum production.

Although sebaceous glands are primarily known for their ability to produce sebum, this is not their only function.

Sebum produced by the sebaceous glands obviously has a hydrating and protective role, helping to limit the evaporation of water from the stratum corneum, friction and the penetration of pathogenic microorganisms, allergens and irritants, but it also allows transport antioxidants, such as vitamin E, to the skin surface, which protects the skin's lipids. To some extent, this contributes to the photoprotection natural to the skin. Furthermore, sebum has antibacterial activity thanks to certain free fatty acids that disrupt the membrane of pathogenic bacteria. It is therefore essential to the balance of the skin microbiota.

Sebaceous glands also participate in the modulation of cutaneous inflammation. They produce pro- and anti-inflammatory molecules depending on the context, contributing both to the immune response against insults and to the restoration of homeostasis. They also play a role in neutralising certain xenobiotics—foreign compounds to the body—by regulating their local metabolism. Moreover, sebaceous glands are actively involved in wound healing: after an injury, they secrete lipid mediators and growth factors that favour the reconstruction of the epidermis.

This multifunctional role of the sebaceous glands is closely linked to their ability to locally produce steroid hormones, notably androgens. They contain all the enzymes necessary for converting cholesterol into active steroids, as well as for transforming adrenal precursors, such as dehydroepiandrosterone sulphate (DHEA-S), into DHEA, then into androstenedione, testosterone and ultimately dihydrotestosterone. This process, catalysed particularly by 5α-reductase type I, is especially active in the sebaceous glands of the face and scalp. This local hormone production directly regulates sebocyte differentiation and the amount of sebum secreted.

Finally, the sebaceous glands closely interact with the cutaneous nervous system. They express receptors for CRH, a molecule released in response to stress by nerves and certain skin cells. CRH modulates lipid production by sebocytes and influences the expression of enzymes involved in steroidogenesis. In parallel, other neuropeptides, such as substance P, released by perisudoral nerve fibres, can stimulate peripheral sebocytes, increasing local secretion and inflammation. These interactions partly explain why psychological stress can exacerbate certain seborrhoeic conditions, notably acne.

The proper functioning of the sebaceous glands is essential to skin homeostasis. When their activity is altered, whether by overproduction, underproduction or qualitative changes in sebum, the balance of the cutaneous microbiota, barrier function and inflammatory regulation of the skin may be compromised. These sebaceous gland imbalances are involved in numerous inflammatory dermatoses, ranging from acne to eczema, through rosacea, psoriasis and seborrhoeic dermatitis.

• The link between the sebaceous glands and acne.

  Affecting up to 85% of adolescents and often persisting into adulthood, acne is the most common skin disease. It is characterised by sebaceous gland hyperactivity driven by androgens at puberty. In acne lesions, the sebaceous glands exhibit a overexpression of the enzyme 11β-hydroxysteroid dehydrogenase type I, which locally increases cortisol and promotes lipid synthesis. Beyond the quantity, sebum composition may also be altered: reduced linoleic acid, excess squalene whose oxidation triggers inflammation, and low vitamin E levels. This is referred to as dyseborrhoea. These changes maintain comedogenesis and skin inflammation. Treatments that reduce sebaceous gland activity, such as isotretinoin, confirm this role: the decrease in sebum production is accompanied by a reduction in lesions but also some cutaneous dryness, both linked to reduced sebaceous function.

• The connection between sebaceous glands and eczema.

  Eczema is characterised by a disruption of the skin barrier, with an increased pH of the stratum corneum, elevated transepidermal water loss and reduced hydration. While most studies focus on keratinocyte-derived ceramide deficiency, sebaceous gland dysfunction is equally important. In patients with atopic dermatitis, sebum production is often reduced, contributing to skin dryness and compromising the hydrolipidic film. Histologically, both lesional and non-lesional skin exhibit sebaceous hypoplasia, and in infantile eczema the glands are poorly developed, with small basal cells devoid of lipids and lacking secretory activity. Sebaceous secretion then increases during adolescence, which explains why many children outgrow atopic dermatitis as sebaceous function normalises.

• The link between sebaceous glands and psoriasis.

  Psoriasis is a chronic inflammatory dermatosis affecting up to 8.5% of adults. Although the histological and immunological changes in psoriasis are well documented, alterations of the sebaceous glands remain poorly studied. On the psoriatic scalp, lesions often show a marked atrophy of the sebaceous glands, with a reduction in their size and number, sometimes complete in over half of cases. However, gland size does not appear to correlate with clinical severity or with inflammatory signs, and the average sebum content in psoriatic skin is comparable to that of healthy skin. Some hypotheses suggest that growth factors such as TGF-α and epidermal growth factor, which are overexpressed in psoriasis, might inhibit sebocytes, but further work is needed on this topic.

• The relationship between the sebaceous glands and rosacea.

  Rosacea is a common chronic skin disease that manifests primarily as diffuse redness. In patients with papulopustular rosacea, the skin’s barrier function is impaired, with an elevated pH and reduced skin hydration. However, the total sebum amount and sebum excretion rate on the forehead do not differ significantly from those of healthy subjects, nor do they correlate with disease severity. Nevertheless, the sebum lipid composition appears to have an influence. Indeed, individuals with rosacea generally exhibit an increase in myristic acid (C14:0) and a decrease in long-chain and very-long-chain saturated fatty acids. This lipid imbalance likely contributes to the dysfunction of the skin barrier.

• The relationship between sebaceous glands and seborrhoeic dermatitis.

  Seborrheic dermatitis is an inflammatory skin disorder that preferentially affects areas rich in sebaceous glands, such as the scalp, face and upper trunk. Contrary to its name, this condition is not directly linked to an overproduction of sebum. The role of the sebaceous glands in its development is instead attributed to sebum lipid metabolism by the fungusMalassezia, whose lipases hydrolyse the triglycerides present in sebum, decreasing their concentration and increasing that of irritating free fatty acids. This provokes a disruption of the skin barrier, inflammation and desquamation. Seborrheic dermatitis thus results from an interaction between the sebaceous glands, the fungal microbiota and individual susceptibility, without any significant change in the total lipid content.

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