The Journal of Dermatology Vol. 18: 489-499, 1991
Invited article
Pathogenesis and Pathogenesis Related Treatment of Acne Harald P.M. Gollnick, Christos C. Zouboulis, Hirohiko Akamatsu, Ichiro Kurokawa and Anja Schulte Key words: acne; sebaceous gland; keratinization; therapy
Acne is a disease of the second life decade with nearly 100% incidence among both females and males. Acne has an polyetiological background comprized of genetic, racial, endocrine, immunological, environmental, and psychological factors. The polymorphous character of acne ranges from a very mild "physiological" course to a severe disabling acute or chronic inflammatory disease (1). In general, two types of acne have to be considered: 1. an endogenous "natural" type, and, 2. a "non-natural" type provoked by additional endogenous or/and exogenous factors. The target organ in acne is the pilosebaceous follicle. Acne almost exclusively occurs in those areas of the body in which this type of follicle is distributed, in particular, the face, chest, and back. Today, at least four etiological factors are accepted to be responsible for the development and maintenance of acne. These are: a) increased activity of the sebaceous glands, b) disturbed cornification within the pilosebaBy invitation: Presented at the 90th Annual Meeting of The Japanese Dermatological Association, Kyoto, April 27,1991. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin (Chairman: Prof. Dr. Prof. h.c.C.E. Orfanos, M.D.). Reprint requests to: Ass. Prof. Harald P.M. Gollnick, M.D., Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, 1000 Berlin 45, Federal Republic of Germany.
ceous duct, c) increased microbial colonization and d) inflammatory and immunological reactions. However, one factor alone usually is not capable of producing the whole event. Pathogenesis of acne a) In the very beginning of puberty, the sebaceous gland becomes more and more differentiated, increases in size, and changes its sebum composition. The sebaceous gland is under the control of androgens produced by the testes and ovaries, like testosterone (T), or by the adrenals, like dehydroepiandrosteronsulfate (DHEAS). Since acne can start before sexual maturity, the initial stimulus for the sebaceous gland may derive from the adrenals (2-4). Free testosterone, which enters the basal sebocytes, is converted within the cytoplasm by 5-a-reductase to 5-a-dehydrotestosterone (DHT). DHT then is coupled with high affinity to a specific cytoplasmic receptor protein translocating the androgen receptor complex to the nucleus of the cell. Here the commands are given for further cellular events leading to the biosynthesis of certain factors for the regulation of sebocyte functions. DHT is further metabolized to 3-a-androstanediol (3-a-DIOL) glucuronide and an inactive further metabolite, 3-a-DIOL glucuronide (3-a-DIOL G). The proliferation and differentiation of the sebaceous glands mostly depends on the amount of cellular uptake of androgens, the activity of 5-areductase, and the receptor affinity. The question has arisen as to whether the 3-a-androstanediolglucuronide itself can locally stimulate the sebaceous gland. Interestingly, it was found that, under treatment with similar doses of isotretinoin, 3-a diol-glucuronide but not DHT was significantly decreased in men; in women, in contrast, DHT and 3-a-DIOL were lowered.
490
Gollnick et al
Most probably, persistent 5-a-reductase activity of prostatic origin is responsible for the unchanged DHT levels in men. The hypothesis that the sebaceous gland metabolites support the pool of androgens in the general circulation should be proven in the near future (5, 6). With regard to the circulating plasma androgens and their metabolites in acne, there is no evidence that the "average" acne-patient is characterized by increased levels of circulating hormones with androgenic potency (reviewed in 1). However, there are several data showing that, in the non-natural course of acne, endogenous hyperandrogenism, due either to enhanced production, as in hyperplasia of androgen producing organs, in tumors, or in disturbances of the pituitary gland, in hypothyreoidism, and in severe obesity with changes of the sexual hormone binding globulin levels, hyperseborrhoea, acne, hirsutism, and alopecia (SAHA-syndrome) can be provoked (Fig. 1).
physiological acne
'over 20 years' acne
Invited article
Pathogenesis and Pathogenesis Related Treatment of Acne Harald P.M. Gollnick, Christos C. Zouboulis, Hirohiko Akamatsu, Ichiro Kurokawa and Anja Schulte Key words: acne; sebaceous gland; keratinization; therapy
Acne is a disease of the second life decade with nearly 100% incidence among both females and males. Acne has an polyetiological background comprized of genetic, racial, endocrine, immunological, environmental, and psychological factors. The polymorphous character of acne ranges from a very mild "physiological" course to a severe disabling acute or chronic inflammatory disease (1). In general, two types of acne have to be considered: 1. an endogenous "natural" type, and, 2. a "non-natural" type provoked by additional endogenous or/and exogenous factors. The target organ in acne is the pilosebaceous follicle. Acne almost exclusively occurs in those areas of the body in which this type of follicle is distributed, in particular, the face, chest, and back. Today, at least four etiological factors are accepted to be responsible for the development and maintenance of acne. These are: a) increased activity of the sebaceous glands, b) disturbed cornification within the pilosebaBy invitation: Presented at the 90th Annual Meeting of The Japanese Dermatological Association, Kyoto, April 27,1991. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin (Chairman: Prof. Dr. Prof. h.c.C.E. Orfanos, M.D.). Reprint requests to: Ass. Prof. Harald P.M. Gollnick, M.D., Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, 1000 Berlin 45, Federal Republic of Germany.
ceous duct, c) increased microbial colonization and d) inflammatory and immunological reactions. However, one factor alone usually is not capable of producing the whole event. Pathogenesis of acne a) In the very beginning of puberty, the sebaceous gland becomes more and more differentiated, increases in size, and changes its sebum composition. The sebaceous gland is under the control of androgens produced by the testes and ovaries, like testosterone (T), or by the adrenals, like dehydroepiandrosteronsulfate (DHEAS). Since acne can start before sexual maturity, the initial stimulus for the sebaceous gland may derive from the adrenals (2-4). Free testosterone, which enters the basal sebocytes, is converted within the cytoplasm by 5-a-reductase to 5-a-dehydrotestosterone (DHT). DHT then is coupled with high affinity to a specific cytoplasmic receptor protein translocating the androgen receptor complex to the nucleus of the cell. Here the commands are given for further cellular events leading to the biosynthesis of certain factors for the regulation of sebocyte functions. DHT is further metabolized to 3-a-androstanediol (3-a-DIOL) glucuronide and an inactive further metabolite, 3-a-DIOL glucuronide (3-a-DIOL G). The proliferation and differentiation of the sebaceous glands mostly depends on the amount of cellular uptake of androgens, the activity of 5-areductase, and the receptor affinity. The question has arisen as to whether the 3-a-androstanediolglucuronide itself can locally stimulate the sebaceous gland. Interestingly, it was found that, under treatment with similar doses of isotretinoin, 3-a diol-glucuronide but not DHT was significantly decreased in men; in women, in contrast, DHT and 3-a-DIOL were lowered.
490
Gollnick et al
Most probably, persistent 5-a-reductase activity of prostatic origin is responsible for the unchanged DHT levels in men. The hypothesis that the sebaceous gland metabolites support the pool of androgens in the general circulation should be proven in the near future (5, 6). With regard to the circulating plasma androgens and their metabolites in acne, there is no evidence that the "average" acne-patient is characterized by increased levels of circulating hormones with androgenic potency (reviewed in 1). However, there are several data showing that, in the non-natural course of acne, endogenous hyperandrogenism, due either to enhanced production, as in hyperplasia of androgen producing organs, in tumors, or in disturbances of the pituitary gland, in hypothyreoidism, and in severe obesity with changes of the sexual hormone binding globulin levels, hyperseborrhoea, acne, hirsutism, and alopecia (SAHA-syndrome) can be provoked (Fig. 1).
physiological acne
'over 20 years' acne
