Steroid sulfatase activity in epidermis of acne-prone and non-acne-prone skin of patients with acne vulgaris

Milewich, L.

doi:10.1001/archderm.126.10.1312

Cited by 7 publications

(7 citation statements)

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“…In support of the latter, T synthesis by SZ95 sebocytes in vitro derives mainly from DHEA [93]. DHEA-S is hydrolysed in the skin to DHEA by steroid sulfatase, detected in sebaceous glands and dermal papilla cells (DPCs) of terminal HFs [94, 95]. Monocytes also exhibit steroid sulfatase activity, thus introducing the variable of “inflammation” to cutaneous androgen production [96].…”

Section: Steroidogenesis In the Skinmentioning

confidence: 99%

Steroidogenesis in the skin: Implications for local immune functions

Slominski

Zbytek

Nikolakis

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

318

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The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases.

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Section: Steroidogenesis In the Skinmentioning

confidence: 99%

Steroidogenesis in the skin: Implications for local immune functions

Slominski

Zbytek

Nikolakis

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

318

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“…The distribution and strong activities of various hydroxysteroid dehydrogenases in human sebaceous glands in acne-prone as compared to non-acne skin have long been observed [67] . While there was no difference in the rates of enzymatic hydrolysis of steroid sulfatase between the freshly obtained epidermal tissue of acne-prone and normal skin [20] , a novel non-estrogenic inhibitor of steroid sulfatase, 6-[2-(adamantylidene)hydroxyben zoxazole]-O -sulfamate, was shown to effectively block the enzyme in the skin leading to a reduction of sebum secretion in animal studies [68] . However, although an exclusive predominance of type 1 5 -reductase has been demonstrated in sebaceous glands, with higher enzyme activity in facial skin than in nonacne-prone skin [27,69] , there seems to be no relationship between the activity of 5 -reductase or 17 -HSD in sebaceous glands and the presence or absence of acne in both sexes [70] .…”

Section: Expression Of Steroidogenic Enzymes In Acne Patientsmentioning

confidence: 99%

“…Five major enzymes are involved in the activation and deactivation of androgens in skin [19] . In a fi rst step, steroid sulfatase hydrolyzes DHEA-S to DHEA in skin [20] . The sebaceous gland has been suggested to carry out this reaction since strong steroid sulfatase immunoreactivity was found in acne skin, primarily associated with the monocytes infi ltrating the lesions [21] , but further evidence is required to corroborate this preliminary report.…”

Section: Androgen Metabolism and Its Transcriptional Regulation In Thmentioning

confidence: 99%

Sexual Hormones in Human Skin

Zouboulis¹,

Chen²,

Thornton³

et al. 2007

Horm Metab Res

323

232

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“…This conversion requires steroid sulfatase to produce free DHEA, 3βHSD1 to convert DHEA to androstendione and 17βHSD type 5 to convert androstendione to testosterone, all of which are expressed in skin [132, 147, 158–160]. Testosterone synthesis by sebocytes can be stimulated by the addition of pregnenolone [157], indicating the involvement of CYP17A1 and suggesting that some testosterone synthesis derives from endogenous cutaneous cholesterol.…”

Section: Steroidogenic Activities Of the Skin And Subcutismentioning

confidence: 99%

On the role of skin in the regulation of local and systemic steroidogenic activities

2015

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The mammalian skin is a heterogeneous organ/tissue covering our body, showing regional variations and endowed with neuroendocrine activities. The latter is represented by its ability to produce and respond to neurotransmitters, neuropeptides, hormones and neurohormones, of which expression and phenotypic activities can be modified by ultraviolet radiation, chemical and physical factors, as well as by cytokines. The neuroendocrine contribution to the responses of skin to stress is served, in part, by local synthesis of all elements of the hypothalamo-pituitary-adrenal axis. Skin with subcutis can also be classified as a steroidogenic tissue because it expresses the enzyme, CYP11A1, which initiates steroid synthesis by converting cholesterol to pregnenolone, as in other steroidogenic tissues. Pregnenolone, or steroidal precursors from the circulation, are further transformed in the skin to corticosteroids or sex hormones. Furthermore, in the skin CYP11A1 acts on 7-dehydrocholesterol with production of 7-dehydropregnolone, which can be further metabolized to other Δ7steroids, which after exposure to UVB undergo photochemical transformation to vitamin D like compounds with a short side chain. Vitamin D and lumisterol, produced in the skin after exposure to UVB, are also metabolized by CYP11A1 to several hydroxyderivatives. Vitamin D hydroxyderivatives generated by action of CYP11A1 are biologically active and are subject to further hydroxylations by CYP27B1, CYP27A1 and CP24A. Establishment of which intermediates are produced in the epidermis in vivo and whether they circulate on the systemic level represent a future research challenge. In summary, skin is a neuroendocrine organ endowed with steroid/secosteroidogenic activities

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Steroid sulfatase activity in epidermis of acne-prone and non-acne-prone skin of patients with acne vulgaris

Cited by 7 publications

References 0 publications

Steroidogenesis in the skin: Implications for local immune functions

Steroidogenesis in the skin: Implications for local immune functions

Sexual Hormones in Human Skin

On the role of skin in the regulation of local and systemic steroidogenic activities

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