Bioscientia Medicina: Journal of Biomedicine & Translational Research eISSN (Online): 2598-0580 Bioscientia Medicina: Journal of Biomedicine & Translational Research Role of Androgen on Physiological Function of Pilosebaceous Unit Inda Astri Aryani1* , Cayadi Sidarta Antonius1, Suroso Adi Nugroho1, Nopriyati1 1Department of Dermatology and Venereology, Faculty of Medicine Universitas Sriwijaya, Palembang. Indonesia. A R T I C L E I N F O A B S T R A C T Keywords: The pilosebaceous unit is a sebaceous gland with hair follicles. One of the Androgen hormones that affects the pilosebaceous unit is androgen, a steroid hormone that Pilosebaceous Unit plays an important role in the expression of the phenotype of men and women. Physiological Androgen consist of testosterone and dihydrotestosterone which are activated by androgen receptors. Androgen in the pilosebaceous unit affect sebum production *Corresponding author: and hair growth. Androgen receptors in the sebaceous glands are found on Inda Astri Aryani sebocytes and in hair follicles in the dermal papillae of hair follicles E-mail address: [email protected] All authors have reviewed and approved the final version of the manuscript. https://doi.org/10.32539/bsm.v5i3.321 1. Introduction cholesterol in pilosebaceous unit and mediated by Skin is the largest organ in human, it is about 1.75 several enzymes such as 5α-reductase, steroid m2 in wide, and consists of various adnexal structures, sulfatase, and 17β-hydroxysteroid dehydrogenases.4 such as hair follicle, nail, and glands. Sebaceous This literature review discusses the pilosebaceous glands, a multilocular structure with connecting unit, androgens, androgen receptors and the influence channels to excretory duct and connected to hair of androgens on the pilosebaceous unit. The aim of this follicle. The size of sebaceous glands varies, even in the review is to understand the role of androgen on the same anatomical area on one person. Sebaceous glands physiological function of the skin, especially the connected to hair is called pilosebaceous unit.1 pilosebaceous unit. Androgen, an endocrine hormone, plays major role in pilosebaceous unit is androgen. Androgen in hair Androgen hormones follicle has a role to stimulate hair growth, and the in Androgens synthesized in the gonads, adrenal sebaceous glands is to stimulate production of glands, and skin. The production of androgen in gonad 2,3 sebum. Androgen synthesized in the gonad, begins with neuronal release from brain to adrenals, and skin. The major active androgens in hypothalamus, then thalamus releases gonadotropin- pilosebaceous unit are testosterone and releasing hormone (GnRH) to portal vein in pituitary. dihydrotestosterone. It was synthesized from Gonadotropin-releasing hormone stimulate the 573 pituitary to secrete luteinizing hormone (LH) and follicle testosterone (Table 2). 5α-reductase enzymes will stimulating hormone (FSH). Luteinizing hormone will convert testosterone to become DHT and it has 2 stimulate interstitial cell, Theca cell in ovary and Leydig isoenzymes (type I and type II). 5α-reductase type I can cell in testis to secrete androgen (Figure 1).5 At 6 weeks be found in sebocytes, especially face sebocytes, sweats of gestation, Leydig cells in the testis will synthesize glands, keratinocytes, and dermal fibroblast. 5α- testosterones. Testosterones is the most circulated reductase type II can also be found in hair follicle. androgens, while 5α-dihydrotestosterones is the result Androgen production in the skin also significantly of testosterone metabolism.6 contributes to the circulated androgen and There are several active androgens circulated in the systemically impactful.7,6,9,10 blood, such as dehydroepiandrosterone sulfate (DHEA- S), androstenedione, testosterone, and 5α- The role of androgen in the pilosebaceous unit dihydrotestosterone (Table 1). Both DHEA-S and The role of androgen in hair follicles androstenedione were synthesized on the adrenal Hair follicles divided into three types: lanugo, vellus glands while both testosterone and 5α-DHT were and terminal (Table 3). Lanugo is prenatal hair. synthesized on the gonads. Later, these androgens Terminal hair is found on scalp, eyebrows, eyelashes at reach the skin via the bloodstream.6 birth. During puberty, vellus is found on genitalia, In female, androgen production is produced by axilla, trunk, and beard in men. Vellus will turn into ovarium with stimulation of hypothalamus. terminal hair follicle under influence of androgen.3 Hypothalamus will release gonadotropin-releasing There are 3 phases of hair follicle growth, named hormone and stimulate anterior pituitary to release anagen, catagen and telogen phase. Some researchers luteinizing hormone (LH) and follicle stimulating also found another phase, called exogenous phase. The hormone (FSH). Later, LH will stimulate Theca cells in longest phase is anagen or growth phase, about 2-7 ovarium and transform cholesterol become years. 11 androstenedione and testosterone. Some Androgens in form of testosterones and 5α-DHTs androstenedione and testosterone will enter circulatory are activated after the binding to its receptors. bloodstream while other will be transformed into Androgen receptors in pilosebaceous unit is found in estrogen in ovarian granulosa cells. Testosterone is 10 keratinocytes, sebocytes, and papillae dermis times lower in female than male.7 cells.6,10,12 Testosterones and 5α-DHTs will diffuse from Apart being produced by gonad cells, androgens blood to cell membrane and binds to androgen also produced in the adrenal glands in form receptors in nucleus (Figure 2).13 dehydroepiandrosterone-androgen (DHEA) and The hair growth is influenced by the interaction of androstenedione stimulated by adrenocorticotropin androgen with androgen receptors in dermal papillae. hormone. With the addition of sulphate, The synthesis of testosterones occurs in the dehydroepiandrosterone-androgen become DHEA- mitochondria of target cells such as pilosebaceous unit sulphate (DHEA-S); becoming the reservoir for DHEA in dermal papillae. After reaching the target cells, and other androgens. DHEA-sulphate has a longer life- cholesterols are broken down under the influence of time than DHEA.8 specific enzymes.14,15 Testosterones is converted into In the skin, androgen production is independent to 5α-DHTs by type 2 5α-reductase enzyme during hypothalamus control. Skin produces testosterone and catalyzation. Later, androgens will stimulate the growth DHT from circulated DHEA-S. The hair follicle papillae of hair follicles in specific area especially those related and sebaceous gland on the skin contain 3β- to secondary sexual characteristics, such as axillary hydroxysteroid dehydrogenase and 17β-hydroxysteroid hair, pubic hair and beard.6,10,13,16 Thera are 3 isoforms dehydrogenase enzymes and involve in synthesis of of 5α-reductase enzyme, namely type 1 5α-reductase, 574 mostly found in hair and type 2 5α-reductase and type androstenediones into stronger androgens such as 3 5α-reductase, mostly found in prostate and testosterones and DHTs. Both androstenediones and epididymis.8,16 (Table 3) testosterones also have been proven to stimulate There is a hypothesis that androgen from circulating secretion of human sebum.6 blood will enter the hair follicles through papillae Sebum production of sebaceous glands is affected dermis bloodstreams. Later, androgens will bind to by androgen level, stronger androgen stimulation, and androgen receptors and will be metabolized into 5α- their binding to androgen receptors. Androgen DHTs. When androgen binds to androgen receptor in receptors can be found in basal layers of sebaceous dermal papillae cells, this will change the production of glands. Sebum production is significantly higher in first paracrine regulating factors and influencing the day of birth in both sexes and persisted until the activities of papilla cells of dermal follicles13 (Figure 3) second months. This condition is found to be related to During and after puberty, androgens will stimulate genitalia crisis. Genitalia crisis is characterized by the development of small and colorless follicles of vellus breast swelling, edema genitalia with hydrocele in male into terminal follicle. Androgens, especially and genitalia bleeding in female. The increasing testosterones will influence the size of dermal papillae production of sebum also found to be related to until the proportion of hair and follicles is reached. This stimulation by androgen, marked by the increase of change is consistent with hair cycle. Testosterone will DHEAS plasm level and persisted in the first 3 months stimulate follicles to produce vellus hair which is of life. High level of androgen in 7 years old is due to colorless in many parts of body and changes it into big increasing production of DHEA-S by adrenal glands hair follicle and produce longer, thicker and more and related to puberty. Later, there is a decreased level pigmented hair. This process will make a more visible of DHEA-S in early adolescent and tend to decrease hair in many parts of body.13 further with age, along with the decrease of sebum 3,4,10 In baldness or hair loss, 5α-DHTs stimulate big hair production. follicle into smaller vellus follicles and produce smaller Weaker androgen hormone, and colorless hair. In androgenic alopecia, testosterone dehydroepiandrosterone sulphate (DHEA-S) is a will be metabolized into 5α-DHTs. If testosterones and significant stimulating factor of sebaceous glands 5α-DHTs are available