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The interconversion of estrone (E1) and 17β-estradiol (E2) is catalyzed by 17β-hydroxysteroid dehydrogenase (17β-HSD) in peripheral steroidogenic organs such as the skin. To investigate gender differences of activity and skin distribution of 17β-HSD in human skin, enzymatic activity was measured in skin homogenates and skin horizontally sliced by 10 µm thickness in vitro. Reductive 17β-HSD (E2 formation from E1) in female skin has a lower substrate affinity than in male skin; Km (Michaelis-Menten constant) of female and male skin is 11.8 ± 6.5 and 2.0 ± 2.0 µM, respectively. Female skin had a tendency to activate estrogen; Vmax (maximum rate) for E2 formation, 5.8 ± 4.0 pmol/min/mg protein, is 1.7 times larger than E1 formation, 3.5 ± 1.5 pmol/min/mg protein, and, on the other hand, male skin tends to deactivate estrogen; Vmax for E1 and E2 is 10.5 ± 6.1 and 4.2 ± 3.7 pmol/min/mg protein, respectively. The concentration of metabolite had a peak value at 80–120 µm from the skin surface. Therefore, these in vitro results suggest that the enzymatic activities of 17β-HSDs have a gender difference in estrogen formation/metabolism and are distributed around the basement layer of the epidermis irrespective of sex. 17β-HSDs distributed around the basement epidermis may be effectively supplied with circulating estrogen from the papillary plexus to maintain the estrogen level in skin. This distribution pattern having a peak surrounding 100 µm from the skin surface indicates the importance for defense from noxae (e.g. detoxication) and maintenance of the internal environment (e.g. biosynthesis of hormones). Future studies should increase sample size and confirm these results by stricter statistical analysis.

The chronic effects of the irritant sodium lauryl sulphate (SLS) on stratum corneum (SC) barrier function, determined by transepidermal water loss (TEWL) measurements and on epidermal cell kinetics, estimated by stratum corneum turnover time (SCTT) determination (dansyl chloride staining method), were investigated in 18 healthy female volunteers. SLS (7.5%) was applied without occlusion for 20 min once daily, over a period of 3 weeks (5 days a week) on dansyl chloride-stained skin and on untreated skin. SCTT of untreated skin (19.3 +/- 0.8 days; mean +/- SEM) was not changed by daily treatment with water (control) (19.3 +/- 2.0) but was significantly reduced by SLS (10.9 +/- 0.6; P less than or equal to 0.0001; compared to controls). However, TEWL was increased in SLS-treated sites 1.5-fold after 4 days of treatment (5.3 +/- 0.6 vs. 3.5 +/- 0.3; P less than 0.001). At the end of the second week, TEWL was increased 2.6-fold and after 3 weeks TEWL was 3.3 times higher than in controls 13.0 +/- 1.6 vs. 3.9, P less than or equal to 0.0001). The intensity of SLS-induced irritation as measured by TEWL was significantly correlated with baseline TEWL (r = 0.50; P less than or equal to 0.02) and significantly negatively correlated with SCTT of SLS treated sites (r = -50; P less than or equal to 0.02) but not with SCTT of untreated skin (r = 0.19).

SUMMARY Using a newly developed suction device, the mechanical properties of forearm and vulvar skin were studied in 22 healthy women, 12 before and 10 after the menopause. The ratio between viscous deformation (Uv) and elastic deformation (Ue) and the biological elasticity, i.e. the ratio between immediate recovery (Ur) and total deformation (Uf), were both significantly lower in vulvar than in forearm skin. Ur/Uf decreased significantly with load in vulvar, but not in forearm skin, whereas Uv/Ue was not load-dependent in either site. Uv/Ue remained constant with age in both test sites, whereas Ur/Uf was significantly lower in post-menopausal women in both forearm and vulvar skin. In vulvar, but not in forearm skin, Uv/Ue was significantly correlated with body height which may be an indicator of mechanical connective tissue properties. Viscous deformation plays a lesser role and biological elasticity is decreased in vulvar compared to forearm skin. Despite differences in mechanical parameters at both sites, age-related changes seem to be similar.

A new animal test for evaluating the skin-irritant capacity of cosmetic and drug preparations and ingredients intended for repeated application is presented. The test is patterned on the 21-day occlusive test on man. Substances are applied 16 times (uncovered) to the skin of rabbits over a 3-wk period. The two parameters of the inflammatory response evaluated (16 times) throughout the test as indices of skin irritation are redness (cumulative irritation score) and fluid accumulation (changes in skinfold thickness). Measurements of these two parameters are highly correlated (r = 0·86; P < 0·001). Results on 60 test materials showed a significant correlation (r = 0·30; P < 0·02) between the cumulative irritation scores obtained on rabbits and those obtained on man. The usefulness and limitations of single-application (Draize type) and multiple-application tests for skin irritation are discussed. Exploratory results with hairless rats and hairless hamsters suggested that these species were not sufficiently responsive to be useful in skin-irritation studies. A radioimmunoassay of skin prostaglandin E disclosed no differences between irritated and control skin, suggesting that this technique cannot be used as an objective measure of skin irritation.

Human subjects were used to evaluate the skin sensitization potential of several substances used in marketed drugs and cosmetics, as well as other chemical agents. The results show that a modified Draize test is a useful, predictive patch-test procedure. Potentially strong sensitizers show a dose-response relationship when a range of concentrations of test material are used (at induction), whereas weak sensitizers may not; thus a range of concentrations of test materials may be used as a means of disclosing the potential of these compounds to produce delayed skin hypersensitivity.