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Androgen receptor in human skin.

Cytosol androgen receptor was assayed in 18 human skin biopsies by an exchange technique with a labelled potent synthetic androgen, methyltrienolone (R 1881), under conditions which measured total (i.e. both free and occupied) binding sites. Androgen binding sites were only present in skin biopsies from patients with marked seborrhoea often accompanied by acne (8 cases) and no sites were detected in normal skin biopsies (7 cases). Three biopsies from seborrhoeic patients, however, did not contain androgen receptor. Although no direct quantitative correlation could be drawn between binding site concentration and sebum excretion, it would seem that the androgen receptor content nevertheless constitutes an important parameter in the study of the hormonal control of seborrhoea.

Adolescent↗

Myocardial infarction, androgen and the skin.

Various indices of masculinity were compared in 48 men who had recovered from myocardial infarction and in their age-matched controls. We found little evidence to support the idea that myocardial infarction is related to increased androgenic stimulation. The patients with myocardial infarction had no increase in plasma testosterone, muscle thickness, sebum excretion rate, maximal sweat secretion rate, male pattern alopecia or density of terminal body hair, but as a group they had a slight increase in skin and bone thickness compared with the controls.

Adult↗

Male-pattern alopecia and masculinity.

Cutaneous processes which are thought to be influenced by androgenic stimulation include the development of male-pattern alopecia, terminal hair distribution, sebum excretion rate, maximal sweat secretion rate and skin thickness. We measured these indices in forty-eight normal men, together with muscle, fat and bone thickness and plasma testosterone. There was a significant correlation between hair density on the forearm, leg and chest, but no other significant correlations were found. We conclude that bald men are no more 'masculine' than those with good scalp hair growth, if masculinity is defined in terms of end-organ response to androgenic stimulation.

Adult↗

Enhanced comedo formation in rabbit ear skin by squalene and oleic acid peroxides.

The comedogenicity of UVA-irradiated and non-irradiated substances (squalene, oleic acid, tetradecane, isopropyl myristate, squalane and liquid paraffin) was evaluated by surface microscopy and histological examination after treating the ventral skin of rabbit ears with these substances. The lipid peroxide levels of these substances were also measured. Squalene itself was scarcely comedogenic but squalene peroxides were highly comedogenic. Both oleic acid and its peroxides were able to induce fairly large comedones and there was a good correlation between the lipid peroxide levels and the size of the comedones. The specimens biopsied from these comedones showed marked hyperplasia and hyperkeratosis of the epithelium in the follicular infundibulum and marked proliferation of the sebaceous glands. Although free fatty acids might play a role in the pathogenesis of acne, it is proposed that squalene and free fatty acids in sebum may be less comedogenic than their peroxides.

Acne Vulgaris↗

An alternative pharmacological approach to the detection of anti-androgenic drugs for acne therapy.

Both testosterone and dihydrotestosterone may be able to stimulate sebaceous glands, and the glandular function may continue under direct testosterone control in the presence of 5 alpha-reductase blockade. Antagonism of sebaceous gland hypertrophy, induced by exogenous testosterone or dihydrotestosterone, has been studied in the hairless hamster using established and experimental drugs applied topically. The results support the proposition that testosterone plays a direct role in mediating sebaceous gland response. This suggests possibilities for the design of sebum inhibitory drugs with minimal systemic anti-androgenic side effects.

Acne Vulgaris↗

Topical azelaic acid and the treatment of acne: a clinical and laboratory comparison with oral tetracycline.

Topical azelaic acid and oral tetracycline were compared in a 6-month double-blind study for treatment of acne vulgaris in 45 male subjects with clinical acne. Their acne was graded, inflamed or non-inflamed, lesions were counted and the density of their skin microflora was measured. Both treatments were of benefit and produced only a few minor side-effects. Although oral tetracycline was more effective than azelaic acid, the differences were only just significant. The average reduction in numbers of cutaneous micrococcaceae and Propionibacterium sp. with azelaic acid treatment was 224 and 30-fold, respectively. In a separate group of 11 male subjects with physiological acne the effect of azelaic acid on sebum excretion rate was assessed, and little change was detected.

Acne Vulgaris↗

A possible role for squalene in the pathogenesis of acne. I. In vitro study of squalene oxidation.

An in vitro study of the oxidation of squalene, and a description of factors acting on this transformation are presented. Thin layer chromatography was used to quantify the products generated by different oxidation processes. The results clearly show that squalene is a highly effective oxygen-scavenging agent. Its oxidation may first induce comedogenesis and, as a secondary event, cause a large reduction in oxygen tension in the human pilo-sebaceous duct. Porphyrins were confirmed to be highly efficient catalytic factors in the squalene oxidation process. The relationships between comedogenesis, bacterial colonization, and the role of sebum in the pathogenesis of acne are discussed in the light of these findings.

Acne Vulgaris↗

Anti-androgen treatment in women with acne: a controlled trial.

Ninety female patients with acne were allocated randomly to one of three groups and treated either with Diane, a high dose cyproterone acetate (CPA) regime with ethinyloestradiol, or Minovlar. The same dose of oestrogen was common to all three treatment groups. Patients were assessed every 2 months for 6 months, by grading for severity of the acne, lesion counts and photography, and subjectively using a visual analogue scale. In addition, bacteriological sampling and sebum excretion rate (SER) measurements were performed. The results showed a clinical improvement in all three treatment groups, but a more rapid and complete response was seen in those groups who received CPA. There was also a consistent trend suggesting a more favourable response in those in the high dose CPA group. Although there was a marked reduction in SER in the groups treated with CPA, there was no correlation between reduction in SER and clinical improvement in individuals, nor could a reduction in the surface bacterial population be shown to be a primary event in the success of anti-androgen therapy. We have shown that the addition of CPA to oestrogen adds significantly to the therapeutic effect in acne and that anti-androgen and oestrogen combinations are more effective than standard oestrogen and progestagen contraceptive pills.

Acne Vulgaris↗

Analysis of human skin surface lipid during treatment with anti-androgens.

Skin surface lipid was collected from the foreheads of patients during a study of anti-androgen therapy for acne, and analysed for free fatty acid composition and triglyceride fatty acids. Both sebum excretion rate and bacterial flora decreased during therapy but only the ratio of free fatty acid to total glyceride plus free fatty acid changed, falling in all groups during therapy. No differences in lipid composition were detected in relation to individual therapy but patients admitted at the start of the trial, had, overall, a different lipid composition to those admitted later and had lower surface microbial counts.

Acne Vulgaris↗

Frictional properties of human skin: relation to age, sex and anatomical region, stratum corneum hydration and transepidermal water loss.

Differences in the dynamic skin friction coefficients (mu) were investigated with respect to age, sex, and anatomical region. A total of 29 volunteers consisting of seven young females, seven old females, seven young males, and eight old males participated in the study. Measurements were obtained from II anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. The friction data were compared with stratum corneum hydration and transepidermal water loss (TEWL). The dynamic friction coefficient did not vary significantly between age and sex groups but varied considerably among the anatomical regions of the body. The forehead and postauricular had the highest mu (0.34 +/- 0.02) while the abdomen had the lowest (0.12 +/- 0.01); the remaining regions had an average mu value of 0.21 +/- 0.01. Similarly, no sex differences were observed for TEWL and stratum corneum hydration. Capacitance was only significantly lower on the palms of the elderly. Regional differences showed a higher state of hydration on the forehead and postauricular as well as the upper arm, upper and lower back when compared with the volar forearm. TEWL was generally lower in the elderly on all anatomical regions except the postauricular and palm. A significant correlation was established between mu and capacitance for most regions. Between mu and TEWL significant correlation was observed only on the palm and thigh. These findings suggest that frictional properties of skin are dependent on more than water content or non-apparent sweating and the role of sebum secretion is suggested as one possible factor.

Adult↗

Clinical, ultrasound and hormonal markers of androgenicity in acne vulgaris.

Androgenic stimulation of sebaceous glands is an important factor in the development of acne. We examined 36 females (aged 14-34 years), selected because none had received oral contraceptives, anti-androgen therapy, or systemic antibiotics during the previous year, or isotretinoin therapy, prior to their participation in the study. Subjects were divided into groups on the basis of acne severity, as follows: physiological, mild and moderate. Only two patients had polycystic ovaries on ultrasound examination. Seven patients had irregular menses; none had evidence of hirsutism. We found that the severity of acne, based on the acne grade, was highly correlated with the inflammatory lesion count, and less correlated with the sebum excretion rate. Either acne grade or inflammatory lesion count could be related to some of the five androgenic hormone determinants; free testosterone (TESTOS), delta 4 androstenedione (DELTA 4), sex hormone binding globulin (SHBG), dehydroepiandrostenedione sulphate (DHEAS) and dihydrotestosterone (DHT). Multiple linear regression analysis determined the best model for predicting ACNE scores as involving DELTA 4 and DHEAS (positive effects), and SHBG (negative effect), P < 0.005, R2 = 0.36). In none of the patients were the levels of DHEAS or SHBG outside the normal range. The findings in the two patients with polycystic ovaries did not differ significantly from those in the remainder of the patients.

Acne Vulgaris↗

Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro.

BACKGROUND: Nuclear hormone receptors are important in the regulation of epidermal differentiation and have been implicated in lipid metabolism. In particular, there is evidence suggesting that the activation of peroxisome proliferator-activated receptors (PPARs) is an important factor in the regulation of sebocyte lipogenesis. OBJECTIVES: To determine the role of PPARs, farnesoid X receptor (FXR) and other orphan nuclear hormone receptors in sebaceous gland function in vitro by investigating the biochemical effects of appropriate ligands, and by establishing the RNA and protein expression patterns of a number of nuclear receptors in sebaceous glands ex vivo. METHODS: Human chest sebaceous glands were maintained in vitro as freshly isolated and as 7-day cultured whole organs. We then studied the effects of appropriate ligands on the glandular rates of lipogenesis and DNA synthesis, as well as determining the mRNA (reverse transcription-polymerase chain reaction) and protein expression patterns (immunohistochemistry/immunoblotting) of the nuclear hormone receptors of interest. RESULTS: PPAR ligands, but not FXR ligands, inhibited sebaceous lipogenesis, in particular the PPARalpha ligands LY 171883 and WY 14643, and the PPARgamma ligands BRL 49653 and 15-deoxy-Delta-12,14-prostaglandin J(2). We detected RNA expression of PPARalpha, PPARbeta, PPARgamma, retinoid X receptor alpha, liver X receptor alpha (LXRalpha) and pregnane X receptor but not FXR in freshly isolated and 7-day maintained sebaceous glands. PPARalpha, PPARbeta, PPARgamma and LXRalpha protein were detected in nuclear extracts of sebaceous glands. CONCLUSIONS: We conclude that activation of nuclear hormone receptors, in particular activation of PPARalpha and PPARgamma, can regulate lipogenesis in human sebaceous glands. As suppression of sebum secretion is associated with reduced acne activity, the nuclear hormone receptors involved may open new avenues in the development of novel acne treatments.

Cell Differentiation↗

Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases.

BACKGROUND: Human tissue kallikreins are a gene family (KLK1-KLK15) encoding for 15 secretory serine proteases (hK1-hK15). Two tissue kallikrein proteins, hK5 and hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG) and appendages. hK8 was also shown to be secreted via lamellar granules and numerous KLK mRNAs were previously identified. KLKs are believed to be responsible for desquamation of corneocytes and sebum, sweat and hair maturation. OBJECTIVES: To demonstrate immunohistochemically the expression of hK6, hK8 and hK13 in normal skin tissue and to show an increased cell number expressing kallikrein mRNAs and proteins in psoriasis vulgaris (PV) and atopic dermatitis (AD). METHODS: Samples of normal, PV and AD skin were obtained. hK6-, hK8- and hK13-specific antibodies were produced and used for immunohistochemical analysis. Multiple KLK mRNAs were synthesized and used for in situ hybridization study. RESULTS: Three other hKs, namely hK6, hK8 and hK13, were immunohistochemically identified as new skin serine proteases in the whole SC, SG, sebaceous glands, eccrine sweat glands, hair follicles and nerves. We also demonstrated an increased number of cells expressing KLK mRNAs and hKs in PV and AD. In PV, KLK mRNAs/hKs were predominantly expressed in the upper epidermis. In AD, hK distribution was rather diffuse and expanded into the lower epidermis. CONCLUSIONS: The colocalization of various hKs seems to be essential for the regulation of serine protease activity in skin and for steady desquamation and skin barrier function. Moreover, the increased number of cells expressing multiple KLK mRNA and hK in PV and AD could be a clue to elucidate their pathogenesis.

Adult↗

Fel d I levels in cat anal glands.

BACKGROUND: Major cat allergen Fel d I is produced consistently by skin and by sebaceous glands before being spread on the fur. OBJECTIVE: Since cats have tubular anal glands secreting sebum, proteins and lipids, we looked at the possible presence of Fel d I in these secretions and compared the levels found to those already reported in other cat tissues or secretions. METHODS: Thirty-seven cats were studied. Fel d I dosage in the anal sacs' secretions was performed using an enzyme linked immunosorbent assay (ELISA) method and total protein evaluation by the Bradford's method. RESULTS: The geometric mean Fel d I concentration was 41 U/g secretion which represents 3.4% of the total protein levels. This amount is the highest ever reported in cat tissues or secretions. CONCLUSION: The close association of Fel d I protein with skin sebaceous glands and anal sacs both with holocrine function and lipids' secretions in one hand, and the homology of chain I of Fel d I with some steroid-binding proteins in other hand, suggest a possible physiological role for Fel d I in the regulation of lipids on skin and cat fur.

Allergens↗

Seborrhoea--an indicator for poor clinical response in acne patients treated with antibiotics.

The relationship between sebum excretion rate (SER) and clinical improvement was investigated in 255 acne patients treated for 6 months with either oral erythromycin (1 g/day), minocycline (100 mg/day), oxytetracycline (1 g/day) or cotrimoxazole (400 mg/day); topical therapy was 5% benzoyl peroxide. In all but the cotrimoxazole treated group, there was a significant correlation between a high SER and reduced clinical response. This was particularly evident in those patients with an SER of greater than 2.5 micrograms/cm2/min. These patients showed only 17% improvement compared with 100% improvement in those subjects with an SER of 1.0 micrograms/cm2/min or less. The presence of obvious seborrhoea in a patient who has failed to respond to an adequate 6-month course of antimicrobial therapy, should indicate the earlier rather than later use of isotretinoin for their acne.

Acne Vulgaris↗

The microaerophily and photosensitivity of Propionibacterium acnes.

The effect of oxygen on the in vitro propagation of Propionibacterium acnes was investigated under defined culture conditions. This micro-organism is the predominant bacterial resident within the pilosebaceous follicles of sebum-rich areas of human skin. The organism was grown in continuous culture in defined synthetic medium with glucose as the main carbon-energy source at various air saturation concentrations and in the presence and absence of light. Steady state continuous cultures were achieved at very low oxygen tensions in the presence of light, and at higher levels of oxygen when non-illuminated. Culture biomass yields were higher than those of anaerobic cultures. Bacterial cells were inactivated in the presence of light at high oxygen concentrations because of photosensitization reactions involving excess oxygen and microbial porphyrin species.

Anaerobiosis↗

The epidemiology of Malassezia (Pityrosporon) folliculitis in Singapore.

Seventy patients with a clinical diagnosis of Malassezia folliculitis were studied, of which 48 were confirmed on finding unipolar budding yeastlike organisms on gramstained microscopy or histology specimens. The epidemiologic and clinical features of these 48 cases (M = 44; F = 4) were analyzed. The typical Singaporean patient with Malassezia folliculitis is a young man of mean age 22.2 years with erythematous follicular papules or pustules on the upper back, shoulders, upper chest, and sides of the back. Aggravating factors include heat and sweating. Excessive sebum production may be an important underlying factor.

Adolescent↗

Tinea capitis in adults.

Between 1973 and 1994, 17 cases of tinea capitis in adults were observed in the Dermatology Clinic of the University of Cagliari (Italy). The patients were all women (age range 17-76 years) and came from the district of Cagliari. At the time of referral, they presented with a disease duration varying from 8 to 10 months. The main clinical feature was scalp lesions, but in two cases mycotic lesions on the face were also present. The following dermatophytes were isolated: Microsporum canis (eight cases), Trichophyton violaceum (four cases), Trichophyton mentagrophytes (four cases) and Trichophyton verrucosum (one case). Systemic treatment with griseofulvin or terbinafine led to complete recovery in 40-50 days. In discussing the pathogenesis and transmission mode of the disease, the authors hypothesize that endocrine disorders influencing the secretion and composition of sebum may facilitate dermatophyte invasion of the scalp in the adults.

Adolescent↗