Mechanisms of Androgen Induction of Sebocyte Differentiation

Rosenfield, Robert L.; Deplewski, Dianne; Kentsis, Alex; Ciletti, Nancy

doi:10.1159/000017864

Cited by 149 publications

(129 citation statements)

References 23 publications

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“…Increased sebum accumulation at the skin surface resulted in greasy-looking hair. Recently, peroxisome proliferator-activated receptor (PPAR) isoforms ␣ and ␥ have been shown to play a role in the differentiation of sebocytes (32). Therefore, it is intriguing, that PGI 2 , known to bind to and activate PPAR-␣ (33), was found to be elevated in transgenic skin.…”

Section: Discussionmentioning

confidence: 99%

Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin

Neufang

Fürstenberger

Heidt

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

186

154

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In prostanoid biosynthesis, the first two steps are catalyzed by cyclooxygenases (COX). In mice and humans, deregulated expression of COX-2, but not of COX-1, is characteristic of epithelial tumors, including squamous cell carcinomas of skin. To explore the function of COX-2 in epidermis, a keratin 5 promoter was used to direct COX-2 expression to the basal cells of interfollicular epidermis and the pilosebaceous appendage of transgenic mouse skin. COX-2 overexpression in the expected locations, resulting in increased prostaglandin levels in epidermis and plasma, correlated with a pronounced skin phenotype. Heterozygous transgenic mice exhibited a reduced hair follicle density. Moreover, postnatally hair follicle morphogenesis and thinning of interfollicular dorsal epidermis were delayed. Adult transgenics showed a body-sitedependent sparse coat of greasy hair, the latter caused by sebaceous gland hyperplasia and increased epicutaneous sebum levels. In tail skin, hyperplasia of scale epidermis reflecting an increased number of viable and cornified cell layers was observed. Hyperplasia was a result of a disturbed program of epidermal differentiation rather than an increased proliferation rate, as reflected by the strong suppression of keratin 10, involucrin, and loricrin expression in suprabasal cells. Further pathological signs were loss of cell polarity, mainly of basal keratinocytes, epidermal invaginations into the dermis, and formation of horn perls. Invaginating hyperplastic lobes were surrounded by CD31-positive vessels. These results demonstrate a causal relationship between transgenic COX-2 expression in basal keratinocytes and epidermal hyperplasia as well as dysplastic features at discrete body sites.

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Section: Discussionmentioning

confidence: 99%

Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin

Neufang

Fürstenberger

Heidt

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

186

154

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“…Total RNA was extracted from SZ95 sebocytes and dysplastic oral keratinocytes by using a commercial kit (miniprep; Stratagene). An aliquot of total RNA (1 g) was reverse transcribed into single-stranded cDNA with oligo(dT) 15 (1 g) and Maloney murine leukemia virus reverse transcriptase (200 units; Promega) in a final volume of 25 l as indicated by the manufacturer's instruction. One microliter of reverse transcription mixture was used for PCR reaction.…”

Section: Methodsmentioning

confidence: 99%

“…CRH synthesis in human sebocytes and its control of lipogenesis led us to assess the presence of a feedback mechanism that may involve CRH-R. To investigate this hypothesis, real time quantitative RT-PCR of CRH-R1 and CRH-R2 mRNA levels was performed after treatment of SZ95 sebocytes with CRH, GH, and testosterone, also shown to up-regulate sebaceous lipogenesis (15,16), DHEA and 17␤-estradiol, up-stream and down-stream metabolites of testosterone, respectively (14). CRH was found not to modify mRNA levels of its receptors (Fig.…”

Section: Crh-r Mrna Levels Are Regulated By Growth Hormone (Gh) Andmentioning

confidence: 99%

Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes

Zouboulis

Seltmann²,

Hiroi³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

259

225

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Sebaceous glands may be involved in a pathway conceptually similar to that of the hypothalamic-pituitary-adrenal (HPA) axis. Such a pathway has been described and may occur in human skin and lately in the sebaceous glands because they express neuropeptide receptors. Corticotropin-releasing hormone (CRH) is the most proximal element of the HPA axis, and it acts as central coordinator for neuroendocrine and behavioral responses to stress. To further examine the probability of an HPA equivalent pathway, we investigated the expression of CRH, CRH-binding protein (CRH-BP), and CRH receptors (CRH-R) in SZ95 sebocytes in vitro and their regulation by CRH and several other hormones. CRH, CRH-BP, CRH-R1, and CRH-R2 were detectable in SZ95 sebocytes at the mRNA and protein levels: CRH-R1 was the predominant type (CRH-R1͞CRH-R2 ‫؍‬ 2). CRH was biologically active on human sebocytes: it induced biphasic increase in synthesis of sebaceous lipids with a maximum stimulation at 10 ؊7 M and up-regulated mRNA levels of 3␤-hydroxysteroid dehydrogenase͞⌬ 5-4 isomerase, although it did not affect cell viability, cell proliferation, or IL-1␤-induced IL-8 release. CRH, dehydroepiandrosterone, and 17␤-estradiol did not modulate CRH-R expression, whereas testosterone at 10 ؊7 M down-regulated CRH-R1 and CRH-R2 mRNA expression at 6 to 24 h, and growth hormone (GH) switched CRH-R1 mRNA expression to CRH-R2 at 24 h. Based on these findings, CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induce CRH negative feedback. The findings implicate CRH in the clinical development of acne, seborrhea, androgenetic alopecia, skin aging, xerosis, and other skin disorders associated with alterations in lipid formation of sebaceous origin.

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“…63(3): 347-348, 2001 Dihydrotestoserone (DHT) is a target tissue-produced androgen, which is converted from testosterone by 5α-reductase. DHT is known to have higher affinity with androgen receptors (AR) than testosterone and to play a major role for the development of sebaceous glands and sebum production in the skin [13,14]. The results of our previous study [16] imply the involvement of DHT in the production of primer pheromone in sebaceous glands of the male goat, which is responsible for the "male effect" [1,3] of the male goat.…”

mentioning

confidence: 84%

Induction of Primer Pheromone Production by Dihydrotestosterone in the Male Goat.

Iwata

Wakabayashi

Matsuse

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Castrated goats were treated with dihydrotestosterone (DHT) for four weeks. Skin samples were collected from the head and the rump regions before and after the DHT treatment. The primer pheromone activities of these samples were assessed neurophysiologically by recording electrophysiological manifestations of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity. Pheromone activity was detected in both the head and rump skin samples following the DHT treatment, although the development of sebaceous glands was limited to the head region. Taken together with our previous finding that testosterone treatment results in the appearance of primer pheromone activity in the skin sample of the head region but not of the rump region, these observations suggests that the regional difference of pheromone production would be ascribed to intrinsic expression levels of 5α-reductase, an enzyme converting testosterone to DHT.KEY WORDS: caprine, dihydrotestosterone, pheromone.J. Vet. Med. Sci. 63(3): 347-348, 2001 Dihydrotestoserone (DHT) is a target tissue-produced androgen, which is converted from testosterone by 5α-reductase. DHT is known to have higher affinity with androgen receptors (AR) than testosterone and to play a major role for the development of sebaceous glands and sebum production in the skin [13,14]. The results of our previous study [16] imply the involvement of DHT in the production of primer pheromone in sebaceous glands of the male goat, which is responsible for the "male effect" [1,3] of the male goat. Specifically, four weeks treatment of castrated goats with testosterone resulted in the appearance of primer pheromone activity in the skin sample of the head region but not of the rump region. Much higher immunoreactivities to 5α-reductase and androgen receptor were expressed at the sebaceous glands of the head region than those of the rump region. Based on these findings we assumed that the regional difference of the responsiveness to testosterone was due to different enzymatic activities of 5α-reductase determining local DHT availability. In order to test this hypothesis, skin samples were collected from the head and the rump regions of castrated male goats which had been treated for 4 weeks with DHT. These samples were then assessed for pheromone activity and the development of sebaceous glands as an indicator of sebum production.For the present study, three long-term (>1 year) castrated Shiba goats were obtained from the closed colony at the experimental station of the University of Tokyo. Each animal was implanted subcutaneously with six Silastic capsules (1 cm × 1 cm, Dow Corning, Midland, MI, U.S.A.) each of which contained 1 g of DHT (Wako Co., Osaka, Japan). Skin sampling was conducted on Day 0 (the day of DHT implantation) and on Day 28. For sampling, the goat was anesthetized, and a square (1 cm × 1 cm) of skin was excised from the head and the rump region using a scalpel as described previously [7,16].The bioassay for pheromone activity in skin sample was carri...

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Mechanisms of Androgen Induction of Sebocyte Differentiation

Cited by 149 publications

References 23 publications

Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin

Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin

Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes

Induction of Primer Pheromone Production by Dihydrotestosterone in the Male Goat.

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