Sebum is an oily substance secreted by the sebaceous gland. Sebaceous glands form part of the pilosebaceous unit. They open at the junction of the infundibulum and isthumus of the hair follicle.
Structure of Sebaceous Gland The sebaceous gland consists of lobes or acini, each with a duct. These ducts converge on the main sebaceous duct which opens into the pilary canal. The pilary canal opens onto the surface of the skin by widely dilated follicular orifices.
Each sebaceous lobule consists of an outer layer of undifferentiated germinative cell with a large nuclei. Sebaceous gland is Holocrine. Its secretion is formed by the complete disintegration of the glandular cells.
Sebogenesis Cells differentiate towards the centre. Lipid accumulate. The cells increase in size. The cytoplasm becomes pale and vacuolated. Finally the cells disintegrate. The mass of lipid along with cellular debris is discharged into sebaceous duct as sebum.
Receptors Androgen receptors are present in both the gland and the duct. Peroxisome proliferators – activated receptors (PPARs) All 3 subtypes – (α, β, δ) of PPAR receptors are expressed by the sebocytes. PPAR δ1 is expressed more in the ductal cells of normal skin.
These receptors help in lipid droplet formation. Sebocytes also express Melanocortin receptors - MC1 and MC5. They are target cells for α – melanocyte stimulating hormone (α – MSH)
Distribution of Sebaceous glands Present everywhere in the body except on the palms and soles. More on the face, scalp, upper trunk, external auditory meatus and anogenital surfaces. Face and scalp - 400/cm² to 900/cm². Elsewhere there are < 100 glands/cm²
Modified Sebaceous glands Meibomian glands of eyelids. Tyson glands of prepuce. Margins of lip (Fordyce’s spots) . Montgomery’s tubercules on areola of nipples. On the mucocutaneous surfaces of female genitalia. Ectopic glands in cervix uteri and tongue.
Lipid production varies according to site. 5 - 10 µg/cm² on the limbs. 150 - 300 µg/cm² on the face. Free fatty acids are produced by breakdown of Triglycerides by lipases secreted by bacteria ( Propionibacterium acnes and P. granulosum) .
Sebum is present at birth - vernix caseosa. Present for few postnatal months – maternal androgens Enlarge at puberty , due to androgen influence. Peak sebum secretion during adolescence. Unchanged during adulthood . Become larger in old age, because cell turn over is decreased
ANDROGENS Androgens are the most important hormones controlling sebaceous activity in both sexes. This is the reason for enlargement of sebaceous glands at puberty. The most effective endogenous androgens are Testosterone 5α – Dihydrotestosterone (5α – DHT) 5α – Androsterone - 3β -17β - diol
5α DHT is 5-10 times more potent than testosterone. Testosterone is converted to 5α DHT by the action of 5α reductase. This enzyme has 2 isoforms of which type II is more important for androgenic control.
Other enzymes responsible for interconversion of androgens are: 3 β Hydroxysteroid dehydrogenase (3 β HSD) 17 β Hydroxysteroid dehydrogenase (17 β HSD)
OESTROGENS Larger doses oppose the endogenous stimulation of androgens. Site of action - is at androgen synthesis and not at the level of sebaceous gland. The major active oestrogen is Oestrodiol.
PROGESTERONE Progesterone is a competitive inhibitor of 5α reductase and is expected to reduce sebaceous gland activity. But its sebosuppressive effect is minimal.
Pituitary Hormones Pituitary hormones can directly or indirectly cause increase in sebaceous secretion. These include: ACTH Growth hormone Gonadotrophins α MSH
Sebaceous activity is also increased in Pregnancy and Lactation. The sebaceous glands are not innervated. Unresponsive to administration of neurotransmitters like Acetylcholine and epinephrine.
Functions of sebum Barrier Function Emulsification Antifungal activity Anti bacterial action Protection against Sunburn Vitamin D Precursor Vitamin E production
Sebum in Dermatological conditions Sebum production is decreased in disorders which manifest as dry skin – Atopic dermatitis Contact dermatitis Ichthyosis.
In Acne Vulgaris Sebaceous secretion is increased in acne. The composition of sebum in acne also changes: Higher levels of Squalene and wax esters. Lower levels of fatty acids.
But the principal role of Sebum in Pathogenesis of Acne is - Its capacity of evoking inflammation. Its provision of substrate for the growth of intrafollicular anaerobic bacteria. Inducing faulty follicular keratinisation resulting in comedone formation.
Sebum in systemic disorders Increased sebum secretion is seen in: Adrenal Hyperplasia Ovarian tumours Polycystic ovarian disease Acromegaly Parkinsonism After phenothiazine drugs
Sebum secretion is decreased in: Primary and secondary hypogonadism Adrenal insufficiency Panhypopituitarism Starvation
ANTI ANDROGENS Suppress the generation of androgens. Inhibit peripheral metabolism of androgen in target tissues. But use is limited to women because of the feminizing effects in men.
These include: Oestrogen Cyproterone acetate Spironolactone Ketoconazole Cimetidine
Role of Isotretinoin Isotretinoin (13 cis – RA) reduces the size of sebaceous glands and markedly suppresses sebum production. Mechanism of action: Prolongation of maturation of basal sebocytes. Inhibition of terminal sebocyte differentiation. Reduction of 5α reductase activity in liver and skin.
Eccrine glands Primary sweat glands responsible for thermoregulation. Present all over the body Merocrine glands. They open directly onto the surface of the skin. Smaller in size
Apocrine glands Present only in axillae, areola and perianal region. Open into the hair follicle. Larger in size. Not functional until puberty. Decapitation secretion. Apocrine secretion is protein rich, milky white in colour and odourless when first formed. Alteration by bacteria causes odour.
Apoeccrine glands Mixed type of sweat glands. Share morphological and functional features of both eccrine and apocrine glands. Develop during puberty. Open directly onto skin surface. Larger than eccrine glands and smaller than apocrine glands. Constitute about 10 – 45 % of all glands in axilla.
Control of sweat It is under : Thermal Osmotic Emotional Gustatory
Thermal control Thermoregulatory sweating occurs all over the body, but more on the face and upper trunk. When central core temperature exceeds temperature set point, sweating occurs. Excessive body heat is dissipated by evaporation of sweat. One litre of evaporated sweat removes about 585 kilocalories of heat from the body.
Thermosensitive receptors are present in preoptic area and anterior hypothalamus. They are also triggered by a rise in skin temperature. But the effect of core temperature rise is 9 times more efficient than skin temperature rise, in stimulating sweating.
Osmotic control Hyperosmolarity results in an elevation of the temperature set point and reduced sweating. As sweat is hypotonic, this is a response to conserve further water loss.
Emotional control Mental stimuli also produce sweating. Especially on the palms and soles. The responsible centres are within the frontal region of the brain.
Gustatory control After eating certain foods, sweating on the lips, forehead and nose occurs physiologically in many people. Hot spicy foods are the most common cause. Gustatory hyperhidrosis also occurs in pathological conditions involving the autonomic nervous system.
Innervation of Eccrine gland Sweat glands are innervated by postganglionic sympathetic fibres. These are slow conducting nonmyelinated C fibres. Acetylcholine is the principal neurotransmitter. Physiological sweating is under cholinergic control and partly adrenergic control.
Mechanism of sweat secretion Stimulation of neuronal outflow Release of acetylcholine ACH reacts with receptor in secretory cell membrane Elaboration of nearly isotonic sweat from the secretory coil Modification of primary sweat by reabsorbtion of NaCl to produce hypotonic eccrine sweat
Composition of sweat Odorless, colorless, hypotonic solution Sp. Gravity – 1.005 pH – between 4.5 & 5.5 Contents – sodium, chloride, Potassium, urea, lactate, bic arbonate, ammonia, calcium, glucose, aminoa cids, proteins. Its composition differs from person to person, from time to time, and from site to
Other contents found are : Glandular Kallikrein Kininase C1 esterase Urokinase Cysteine proteinase Epidermal growth factor Drugs like Griseofulvin and Ketoconazole which are excreted.
Functions of sweat Thermoregulation Skin moisturisation (urea) Proinflammatory action (kallikrein) Excretion (drugs, toxins) Desquamation of stratum corneum (lactate)
Alteration in composition of sweat Increased excretion of Electrolytes seen in : Cystic Fibrosis - esp. Sodium Addisons disease Diabetes mellitus Nephrogenic Diabetes insipidus Glycogen storage disease (type I) Adrenogenital syndrome Miliaria
Decrease electrolyte excretion seen in : Thyrotoxicosis Nephrosis Cirrhosis Aldosteronism Cushings syndrome
Excretion of large amounts of amino acids in sweat may occur in - Phenylketonuria Maple syrup urine disease Oast house syndrome Hypermethioninemia Parathyroid dysfunction - calcium excretion Uremia - urea excretion