The acne affected sebaceous gland and its biology
 
SEBACEOUS GLAND BIOLOGY

The human sebaceous glands are endocrine secreting steroidogenic tissues present on all body sites where there is hair. Therefore they are absent on the palms of the hands and soles of the feet just like hair follicles. The most important function of the sebaceous glands, it seems, is the production of the fluid, sebum. Excessive sebum secretion certainly plays a part in acne development.

The size and density of sebaceous glands is much higher on the face, neck, chest and back than on other body sites. Acne therefore occurs mostly at these sites. The number of sebaceous glands remains roughly the same in life but the size normally increases with age. The largest of all sebaceous glands are found on the face.

Sebaceous gland development

The genesis of human sebaceous glands is not fully understood. The sebaceous glands clearly appear in the skin of a human fetus in the 13th to 16th week of pregnancy. The glands grow out from the most superficial bulges of the hair follicles as they develop. When fully grown, the glands remain attached to the hair follicles by a duct through which sebum flows to the hair follicle canal and from there to the skin surface. The development of the glands is closely associated with the differentiation of the hair follicles and the skin epidermis.

The sebaceous glands are fully functional from their formation, significantly increasing sebum secretion within a few hours of birth. Sebum is the first glandular product of the human body and its production peaks in a week after birth, subsiding afterwards. The reason for this early spurt in sebaceous gland production is probably caused by androgens and other hormones passed from the mother to the embryo across the placenta. The sebum secretion rates of the mother and the neonatal baby directly correlate. This correlation is later lost and is independent from breast-feeding. At this time sebum production per unit of skin surface in new born babies is about the same as in young adults and the sequence of transformation of sebaceous glands is the same as in the post natal period.

These events confirm the important role of maternal hormones in the development and activity of the neonatal sebaceous glands. The androgenic stimulation before birth, it appears, comes through the placenta from the mother.

Sebaceous gland as androgen synthesizers

The sebaceous glands are important sites for producing and metabolizing androgens, which are well known for their stimulation of sebum secretion. Most androgens are produced by the gonads and the adrenal glands. Androgens are also produced in the sebaceous glands locally from the precursor hormone dehydroepiandrosterone sulfate (DHEAS), which circulates in the blood after being released from the adrenal glands. Testosterone and dihydrotestosterone, or DHT, are the major androgens that interact with the androgen receptors (AR) to influence the sebaceous glands. DHT is much more potent than testosterone in its interaction with the receptors. However, the exact mechanism of the interaction is unknown.

Androgens regulate sebaceous gland functions through these receptors. The highest density of ARs is found in the sebaceous glands and its distribution in the human body is consistent with known androgen targets and acne sites. People with lower numbers of ARs on their cells are less androgen sensitive. The ARs in the sebaceous glands also regulate cell growth in sebaceous glands. So, fewer ARs on cells means less cell production of sebum and lower rates of cell proliferation.

Sebaceous glands in acne development

It is not clear whether acne is mediated by androgen produced in the sebaceous glands or exogenously produced androgens. All sex steroids produced in the skin are derived from DHEAS. DHEAS is converted to androstenedione in the adrenals as well as in the sebaceous glands. There are two types of an enzyme – 3 beta HSD - which are involved in the conversion, namely, type I and II. In the sebaceous glands it is the type I that converts DHEAS into androstenedione. In the skin another enzyme 17 beta HSD converts the weak androstenedione into the more potent testosterone.

The still more potent DHT is produced from this testosterone by the action of a type I isozyme of the enzyme 5 alpha reductase in the sebaceous gland. The activity of this enzyme is the highest in body sites which are prone to acne. So there is more acne on the face because the enzyme 5 alpha reductase is more active in the sebaceous glands there – in addition to these glands being larger than those seen in other regions of skin.

Sebaceous glands can also synthesize large amounts of free fatty acids locally and are involved in anti-microbial activity transporting antioxidants to the skin surface.

Sebaceous glands as steroidogenic tissues

The sebaceous glands can also produce cholesterol from acetate. This cholesterol is present in the sebum and is used in the cell membrane to form the epidermal barrier. Its use in hormone synthesis has been established only recently. An enzyme catalyses the cholesterol into the steroid pregnenolone, which is converted to DHA by actions of other enzymes. Various antibodies have been found in the hair follicles and sebaceous ducts and glands. All this indicates that skin is a steroidogenic tissue.