Effects of topically applied antiandrogenic compounds on sebaceous glands of hamster ears and flank organs

Growth of sebaceous glands in the ears and flank organs of castrated male hamsters is dependent on androgen substitution. Taking this for granted, a study was done to compare the effects of topical antiandrogenic treatment in vivo on the morphology and size of sebaceous glands with the concomitant changes in in vitro metabolism of 3H-testosterone. The role of dihydrotestosterone in sebaceous gland stimulation was thereby investigated. Topical treatment was carried out with the androgen antagonist 17 alpha-propylmesterolone (PM), with 4-androsten-3-one-17 beta-carboxylic acid (17 beta-C), and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), both described as specific 4-steroid-5 alpha-reductase inhibitors, and with progesterone (PRO), which is an androgen receptor antagonist with 5 alpha-reductase inhibiting properties. Regrowth of sebaceous glands after castration and substitution with testosterone propionate or dihydrotestosterone could be inhibited by topical PM and PRO. This occurred irrespective of the influence on testosterone metabolism and irrespective of the mode of substitution. 4-MA, on the other hand, while exhibiting strong 5 alpha-reductase inhibition in vitro, was ineffective in reducing sebaceous gland sizes in vivo. The compound 17 beta-C was ineffective in every respect. In no case were systemic antiandrogenic effects on prostates and seminal vesicles observed. Our results support the view that the DHT formation rate has no regulatory function for growth of sebaceous glands in hamsters and that PM and PRO counteract the androgenic stimulus by their competitive antagonistic binding to the androgen receptor, but not by their influence on testosterone metabolism.     

The effect of various treatments on the size of sebaceous glands of hairless mice and hairless hamsters

The effect of castration on the size of sebaceous glands of male hairless mice and male hairless hamsters was studied over a period of 4 weeks. Statistically significant decreases in the size of sebaceous glands were observed. The effects of intracutaneous injections of micronized crystalline suspensions of testosterone, testosterone propionate, testosterone phenylpropionate, testosterone decanoate and nandrolone phenylpropionate on the sebaceous glands of castrated hairless mice, castrated hairless hamsters and intact female hairless hamsters were studied over a period of one week. Highly significant increases in sebaceous gland volume were observed 6–7 days after treatment. The effects of subcutaneous and intracutaneous injections of micronized crystalline suspensions of testosterone on the sebaceous glands of intact male and female hairless hamsters were examined at sites local and distal to the injection. Increases in sebaceous gland volume were limited to local sites in the male but increases were observed locally and distally in the female. There was no difference between subcutaneous and intracutaneous injections.     

Sebaceous gland hyperplasia on rabbit pinna induced by tetradecane

To investigate the pathologic changes of sebaceous glands during comedo formation induced by topically applied substances in a rabbit pinna model, purified tetradecane was inuncted on the ventral aspect of the rabbit pinnas once a day for a week. Histologically, a marked hyperplasia of sebaceous glands, epidermis, and follicular epithelium was seen. These remarkably enlarged sebaceous glands were examined histochemically and ultrastructurally. The acinus size and cell population of the hyperplastic sebaceous gland were significantly increased over those of the normal sebaceous gland. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, normal distribution patterns of sulfhydryl (SH) and disulfide (SS) were seen in the peripheral to differentiating layers in the hyperplastic sebaceous glands. In the terminally differentiated layer, the brilliant SH fluorescence was gradually decreased and the SS fluorescence was gradually increased in intensity, indicating that most SH groups in the sebaceous cells were converted to SS linkages before holocrine secretion. By transmission electron microscopy, several cell layers of undifferentiated sebaceous cells were observed at the periphery of the large sebaceous gland. The differentiating sebaceous cells produced a large number of lipid droplets, which were produced in either rough or smooth endoplasmic reticulum. These cells were abruptly converted into homogeneously electron-dense cells which formed several layers. These homogeneous cells gradually lost their electron density before holocrine secretion. These findings indicate that the sebaceous cells in the hyperplastic sebaceous glands undergo a magnified step-by-step cell differentiation and play a role in slightly modified lipid formation, and that there may be an increased production of sebum in the rabbit pinna model. This is the first report of sebaceous hyperplasia induced by a topically applied substance on skin surface, except for androgens. The hyperplastic sebaceous glands could serve as a model for investigations of sebaceous cell differentiation and lipid formation.     

丹参酮ⅡA磺酸钠抗金黄地鼠皮脂腺增生的研究

目的 探讨丹参酮ⅡA磺酸钠（STS）外用对动物模型皮脂腺增生的影响。方法 选用成年雄性金黄地鼠侧腹皮脂腺斑作为动物模型,采用自身对照法,分别予丹参酮ⅡA磺酸钠、生理氯化钠溶液外涂一侧皮脂腺斑,一天3次,随机分用药0、10、20、30 d 4个时间组。在各时间点用游标卡尺测定两侧皮脂腺斑的面积。HE染色法观察皮脂腺斑组织结构的变化,取组织切片用免疫组化方法检测皮脂腺细胞增殖细胞核抗原（PCNA）的表达,TUNEL法检测皮脂腺细胞的凋亡情况。结果 用药前,两侧皮脂腺斑大小比较差异无统计学意义（P > 0.05）,皮脂腺结构完整,排列紧密,皮脂腺细胞的增殖与凋亡比较差异均无统计学意义（P > 0.05）。随着用药时间的延长,与生理氯化钠溶液对照侧比较,STS侧金黄地鼠皮脂腺斑的面积缩小（P < 0.05）;皮脂腺数目减少,体积变小,排列疏松,用药至30 d时,皮脂腺呈明显萎缩状态;皮脂腺细胞PCNA表达明显下调（P < 0.01）,用药至10 d、20 d时更为明显（P < 0.01）;皮脂腺细胞凋亡亦增加（P < 0.01）,用药至20 d时凋亡显著（P < 0.01）,且皮脂腺中央部细胞的凋亡较周围更为明显。结论 丹参酮ⅡA磺酸钠能缩小金地鼠皮脂腺斑的面积,改变皮脂腺斑的显微结构,可抑制皮脂腺增生。     

Androgen-induced delay of hair growth in the golden Syrian hamster

The golden Syrian hamster flank organ has been used to study the stimulatory effect of androgens on sebaceous glands and hair. Androgens cause the sebaceous glands and hair follicles in this organ to grow. We have made the novel observation that exogenously administered androgen, testosterone propionate (TP), suppresses hair growth in the area surrounding the flank organ. When given in a time-release (systemic) subcutaneous dosage form (pellet), 25 mg TP inhibited the regrowth of clipped hair in peri-flank organ skin for up to 21 days; however, by 28 days hair grew back to the same extent as in controls. The peak serum level of testosterone in TP-treated animals occurred at 14 days, and declined thereafter. When two separate TP pellets (25 mg/pellet) were administered 14 days apart in order to maintain high serum levels for 28 days, the amount of hair regrowth after 35 days was identical to animals receiving a single TP pellet or placebo. This suggests that the systemic level of testosterone was not the only factor in hair regulation. Hair growing within the flank organ appeared to be unaffected by TP administration. In the golden Syrian hamster, androgen, as in humans, can exert stimulatory and inhibitory effects on hair growth depending on the body site. We conclude that this animal model could serve as a useful system to investigate the mechanisms responsible for the opposing effects of androgen on hair growth.     

Acne: endocrinologic aspects

Acne is dependent for its development on several factors, one of which is hormonal. The principal and possibly sole mechanistic link between hormones and acne is sebum, the secretory product of the sebaceous glands which is highly androgen-sensitive. Some but not all, patients with acne can be shown to have systemic androgen abnormalities. In addition, there is evidence to suggest that androgens are metabolized abnormally in the skin, possibly resulting in excessive sebaceous gland secretion. Systemic endocrine therapy of acne is designed to reduce the androgenic stimulation of the sebaceous gland. Such treatment includes the peroral cyclic administration of estrogen for ovarian inhibition and the use of low-dosage glucocorticoid for adrenocortical androgen suppression. Combined estrogen-glucocorticoid treatment induces the most telling effect in reducing sebaceous gland activity.     

Whole mount technique: an improved hamster ear model to evaluate pharmacologic effects on sebaceous glands

An improved and simplified hamster ear model (whole mount technique; WMT) is described. Excised ear skin specimens were incubated in 2N NaBr at 37°C for 2 hours, yielding a sheet of dermis with the sebaceous glands attached. After Sudan III staining, the areas of the sebaceous glands in the sheet were measured with an image analyzing system. The ratios of a mean area of androgen-stimulated sebaceous glands/a mean area of non-treated sebaceous glands (AS/NT) were 2.56 in females and 1.69 in males; these results closely resemble AS/NT ratios found in histological sagittal sections. Over 1.0% concentrations of topically applied cyproterone acetate were highly effective in suppressing the proliferation of sebaceous glands in androgen-stimulated hamsters, as measured by WMT. Since no routinely processed histological sections are necessary and the exact size of a whole sebaceous gland can be obtained by WMT, this method seems to be useful for routine work to assess the efficacy of topically applied anti-comedogenic or anti-lipogenic drugs.     

Hormonal control of hamster ear sebaceous gland lipogenesis

The sites and hormonal control of lipogenesis in hamster ear sebaceous glands are reported. Sebaceous lipogenesis was determined in ear biopsies by incubation with glucose and tracer concentrations of 14C-acetate in buffer. The 14C-labeled lipids were saponified, extracted, and determined by liquid scintillation counting. Histologically, the ears contained many sebaceous glands. The glands of male animals were much larger and more heavily lipid-stained than glands from females. Lipogenesis was almost entirely confined to the sebaceous glands in the dermal stroma. Lipogenesis was considerably higher in ear biopsies from male hamsters than from female, castrate male, or hypophysectomized male hamsters. In contrast to published data using hypophysectomized rats, where dihydrotestosterone potently and testosterone only weakly increased sebum secretion, both testosterone and dihydrotestosterone potently increased lipogenesis in the ears of hypophysectomized male hamsters. Dihydrotestosterone was somewhat more potent than testosterone in the hamster. Hypophyseal hormones do not appear to be essential for androgen stimulated lipogenesis in the hamster. In female hamsters, 5 alpha-androstane-3 alpha, 17 beta-diol, testosterone, dihydrotestosterone, 4-androstene-3,17-dione, and 5 alpha-androstane-3,17-dione produced dose-dependent increases in lipogenesis. From this and other studies, it is suggested that androgens other than dihydrotestosterone could be physiologically important in man and animals in stimulating lipogenesis in sebaceous glands.     

Epitestosterone: a potential new antiandrogen

Epitestosterone (EpiT) is the 17 alpha-hydroxy epimer of testosterone (T) and a natural steroid metabolite. It has previously been shown to be a 5 alpha-reductase inhibitor. We have studied EpiT as an antiandrogen using the hamster flank organ model. One-centimeter silastic capsules of crystalline T or dihydrotestosterone (DHT) were implanted subcutaneously in female Golden Syrian hamsters to provide continuous androgenic stimulation. After 3 weeks, the pigmented spot was measured and the flank organs were fixed for histologic sectioning. The maximum surface area (SA) from a central section of the sebaceous gland and the diameter of hair follicles were measured using a computerized digitizing tablet. Following T and DHT, respectively, there was a significant increase in pigmented spot size (656/382%), sebaceous gland SA (210/315%), and mean hair follicle diameter (80/56%). A 1-cm capsule of EpiT alone had no androgenic effect. Five- and ten-fold doses of EpiT were implanted with T or DHT. Epitestosterone significantly inhibited the T-dependent stimulation of pigment, sebaceous gland, and hair follicle at either 5- and/or 10-fold excess doses. Additionally, a 10-fold dose of EpiT also inhibited DHT-dependent stimulation of all 3 cutaneous structures. We conclude that EpiT was effective as an antiandrogen and had no intrinsic androgenic activity in the hamster flank organ. It probably functions both as a competitive inhibitor of the androgen receptor and as a 5 alpha-reductase inhibitor. Pigment and sebaceous gland growth were more sensitive than the hair follicle to androgen inhibition by EpiT at the time and doses tested.     

Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands,extraocular sebaceous carcinoma and benign sebaceous tumors

The histogenesis of extraocular sebaceous carcinomas is – in contrast to ocular sebaceous carcinomas – unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki‐67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63⁺ K5⁺ progenitors which generate the K10⁺ luminal cells of sebaceous ducts; and (ii) p63⁺ K5⁺ K7⁺ progenitors which finally generate K7⁺ adipophilin⁺ EMA⁺ sebocytes. Without exception, all types of sebaceous tumors contained p63⁺ K5⁺ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin⁺ and/or EMA⁺ mature sebocytes and to K10⁺ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63⁺ K5⁺ cells play a major role.     

The effect of estradiol on the sebaceous gland of the hamster ear and its antagonism by tamoxifen

Summary To evaluate the antagonism between estradiol and tamoxifen in the sebaceous gland of the hamster ear, animals were topically treated, and the size of the sebaceous glands was measured by histoplanimetry. The systemic effects were described by determining the estradiol and testosterone plasma levels and within the testes, and the size of the seminal vesicles and the contralateral sebaceous gland. The administration of 0.1 g estradiol resulted in a diminution in the size of the treated glands but left all other parameters unchanged, indicating a purely local effect. A higher dose of estradiol (1 g) further decreased the size of the treated glands, but this was combined with a systemic effect, i.e. low plasma testosterone, decrease in testis size and a diminution of the contralateral ear gland. Ten micrograms of estradiol maximally suppressed all of the androgen effects without side effects. The administration of tamoxifen alone also decreased the size of the sebaceous glands without side effects, but it did not affect the production or effects of androgens. When administered in combination with estradiol, it antagonized the effects of this hormone completely. We conclude that tamoxifen inhibits the negative effect of estradiol on sebaceous-gland size. It acts predominantly in a systemic manner, because a metabolisation to monohydroxytamoxifen is necessary.     

An updated review of the sebaceous gland and its role in health and diseases Part 1: Embryology,evolution, structure,and function of sebaceous glands

Sebaceous glands are sebum‐secreting components of pilosebaceous units. The embryological development of the sebaceous gland follows that of the hair follicle and epidermal tissue, beginning between weeks 13 and 16 of fetal development. New sebaceous glands do not normally develop following birth, but their size increases with age. Sebocytes express a multitude of hormone receptors and are heavily regulated to secrete sebum by androgens. There is a large increase of sebum excretion at birth and again at puberty, until approximately age 17. In adulthood, sebum production remains stable and declines to zero in postmenopausal women and in men aged 60‐70. Besides the production and release of sebum, sebaceous glands function to lubricate the skin and hair, provide thermoregulation, and exhibit antimicrobial activity. Research has shown sebaceous glands to possess the cellular capability to transcribe genes necessary for androgen metabolism. Dysfunction of the sebaceous gland can be seen primarily in steatocystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma. Sebaceous glands are secondarily involved in acne vulgaris, seborrheic dermatitis, and androgenic alopecia.     

Chronological ageing and photoageing of the human sebaceous gland

The human sebaceous gland undergoes both extrinsic and intrinsic ageing. The latter is associated with morphological changes and alteration in the sebaceous gland activity. The high androgen-dependent sebum secretion in neonates falls during childhood, starts to rise again during puberty and reaches its maximum in young adults. While the number of sebaceous glands remains the same during life, sebum levels tend to decrease after menopause in females, whereas no major changes appear until the eighth decade of life in men. Reduced androgen levels in aged individuals lead to a slow cellular turnover in the sebaceous glands resulting in hyperplasia of the facial sebaceous glands in advanced age. Ultraviolet radiation and immune suppression (cyclosporin A with corticosteroids) represent cofactors for the development of sebaceous gland hyperplasia. Current molecular findings indicate that overexpression of the ageing-associated gene Smad7 and parathormone-related protein correlate with sebaceous gland hyperplasia, whereas c-myc overexpression is associated with enhanced sebum production. On the other hand, down-regulation of the mismatch repair genes hMLH-1 and hMSH-2 may promote the development of sebaceous gland carcinoma. In addition to spontaneous single tumours, sebaceous gland carcinomas have been reported in immune-suppressed transplant recipients (azathiorpine, cisplatin, cyclosporin A) and in association with the Muir-Torre syndrome. Microsatellite instability with a loss of the mismatch repair gene hMSH-2 has been detected in immune suppressed patients and under photo-induced DNA damage. Topical and systemic oestrogens offer treatment options for skin xerosis in menopausal females. A combination of isotretinoin and interferon-alpha may prevent tumour development in patients with Muir-Torre syndrome.     

Steroid hormone receptors and their relevance for sebum production in the sebaceous gland ear model of the Syrian hamster

We determined the capacity of steroid hormone receptors in the sebaceous glands of intact nontreated, castrated, with testosterone substituted castrated male, intact female, and intact with testosterone substituted female animals using the animal ear model of the Syrian hamster. The steroid hormone binding capacity was compared with the sebaceous gland areas and sebogenesis. Intact male animals showed large sebaceous follicles, a high sebogenesis rate, and high capacity for sexual hormone binding proteins. In castrated males, the sebaceous gland areas and sebogenesis were both diminished, and androgen and estrogen receptors were decreased. When the castrated males were substituted with testosterone propionate, the sebaceous glands showed large volumes, high sebum production, and androgen binding activity again. In female animals having small sebaceous follicles and a low rate of sebogenesis, testosterone propionate enlarged the sebaceous glands and increased sebogenesis and the capacity of androgen binding. One can conclude from these data that testosterone is not only the main hormone for sebum production but also induces the synthesis of its own receptor.     

Cloning of the hamster androgen receptor gene

Flank organs of male Golden Syrian hamsters contain sebaceous glands and hair follicles whose morphology and function are highly dependent on androgen, which makes these organs a useful model to study androgen action. In order to investigate molecular mechanisms of androgen action, we cloned a cDNA encoding the hamster androgen receptor (hamAR) by polymerase chain reaction (PCR) amplification of hamster testis cDNA. Nucleotide sequence analysis revealed that the cDNA has the capacity to encode a polypeptide of 900 amino acid. The deduced amino acid sequence was highly homologous to those of androgen receptors (AR) from other species. Western blot analysis of COS1 cells transfected with a vector expressing hamAR revealed that the recombinant ham AR was identical in size to that of endogeneous ham AR expressed in liver, sebaceous glands and testis. We further demonstrated that transfection of the hamAR expression vector into COS1 cells resulted in activation of a luciferase reporter gene containing multiple androgen responsive elements (ARE) in a testosterone-dependent manner. Availability of the recombinant hamAR clone along with the flank organ system should provide a more powerful tool than currently available to investigate androgen action at the molecular level.     

The effects of a nonsteroid antiandrogen, flutamide, on sebaceous gland activity.

Flutamide (alpha,alpha,alpha-trifluoro-2-methyl-4'-nitro-m-propionotoluidide), at daily oral doses of 20 mg/day for 24 days, reduced the number and size of skin sebaceous gland cells, and reduced sebum production in ovariectomized, testosterone-stimulated rats. The weight of the preputial glands was also reduced. Unilateral topical application of flutamide (0.1-3.0 mg/day) to flank organs (androgen-sensitive cutaneous sebaceous structures) of testosterone propionate-treated female hamsters for 14 days resulted in bilateral reductions in flank organ weight and in inhibition of in vitro incorporation of 14-C from sodium [1--14C]acetate into lipids. Flutamide inhibition of flank organ weight paralleled the drug effect on lipogenesis. Unilateral topical application of flutamide to flank organs of intact male hamsters for 14 days resulted in significant bilateral reductions of flank organ weight at doses as low as 0.375 mg/day (the lowest dose tested). These weight changes were marked by reduction in sebaceous gland size, accompanied by focal cytoplasmic degeneration, and reductions in cytoplasmic organelles and in the size of the lipid bodies. Flutamide did not, however, seemingly alter the pattern of endogenous total lipids in sebaceous glands, nor did it alter the pattern of 14-C-incorporation into the lipids of male flank organ epidermis and isolated sebaceous glands, when compared to control, untreated preparations.     

Immunohistochemical staining for androgen receptors: a sensitive marker of sebaceous differentiation.

Androgen receptors (AR) are present in normal skin being localized to the basal and differentiating cells of the sebaceous gland, and as such, sebaceous glands are androgen sensitive tissue. Androgen receptor expression was examined in 43 sebaceous neoplasms including 8 sebaceous carcinomas, 22 sebaceous adenomas, 12 specimens showing sebaceous hyperplasia, and 1 sebaceous epithelioma, as well as in 14 squamous cell carcinomas, 2 clear cell acanthomas, and 35 basal cell carcinomas. Epithelial membrane antigen (EMA) expression was also examined in all of the sebaceous neoplasms. All specimens were fixed in formalin and embedded in paraffin. Diffuse positive nuclear androgen receptor antibody immunohistochemical staining was observed in all samples of sebaceous neoplasms, whereas approximately 60% of basal cell carcinomas showed only focal positivity for nuclear androgen receptor immunoreactivity. Clear cell acanthomas and squamous cell carcinomas were uniformly negative. Whereas all sebaceous neoplasms exhibited immunoreactivity for androgen receptors, the staining pattern was more marked in the nuclei of seboblasts and differentiating sebocytes in the adenomatous, hyperplastic, and epitheliomatous lesions than in the nuclei of the less differentiated sebaceous carcinoma cells. All the sebaceous neoplasms except for sebaceous carcinomas exhibited immunoreactivity for EMA. In the sebaceous carcinomas, EMA staining was absent in the most poorly differentiated specimen, but with increasing differentiation, the carcinomas became immunoreactive to EMA. We have shown that the nuclei of sebaceous neoplasms, including sebaceous gland carcinomas, show immunoreactivity for androgen receptors (AR), that immunohistochemical staining for the presence of AR may be a reliable marker of sebaceous differentiation, and that the AR may be a better marker of sebaceous differentiation than EMA, particularly in poorly differentiated sebaceous carcinomas.     

Hair follicle response of the golden Syrian hamster flank organ to continuous testosterone stimulation using silastic capsules

The hamster flank organ has served as a model to study androgen-dependent responses of the skin, but the quantitative response of hair follicles to androgenic stimulation has been neglected. We assayed the hair follicle response to testosterone (T) and compared it to the response of the sebaceous glands and of the dermal pigment in the Golden Syrian hamster flank organ. Because of biologic variation in male animals and uneven absorption of hormone from parenteral injections, we implanted silastic capsules 0.25, 0.5, 1, and 2 cm in length filled with crystalline T subcutaneously into female hamsters for 6 weeks. Hair follicle response to T was more sensitive than sebaceous gland or pigment. Diameters of hairs under the sebaceous gland increased significantly from control values of 27.7 +/- 1.0 micron to 38.0 +/- 1.6 micron at the lowest dose of T tested, the 0.25-cm capsule (p less than 0.001). There was an increase in the absolute number of hairs under the sebaceous gland as the flank organ enlarged, from 27.9 +/- 9.9 control to 55.3 +/- 5.8 with the 2-cm T capsule. There was no concomitant increase in hair density, 14.4 +/- 3.5 hairs/mm control vs 12.5 +/- 1.1 hairs/mm with the 2-cm capsule. Hair follicles lateral to the sebaceous gland did not show the same response to androgen stimulation. Sebaceous gland and pigmentation responded in a dose-dependent fashion, the maximum effect being achieved with a 1-cm T capsule. We conclude that T affects hair by specifically stimulating growth of individual hairs physically under the sebaceous gland. As the whole flank organ enlarges more hairs are recruited to become larger but no new follicles appear. These studies also confirm that there are different sensitivities to androgen within the various androgen-dependent components of the hamster flank organ, with increase in hair diameter being highly sensitive. This model should be useful for the specific and quantitative assessment of androgenic and antiandrogenic substances on hair growth and ultimately by useful for therapy of hirsutism.     

Androgen metabolism in sebaceous glands from subjects with and without acne.

OBJECTIVE: To determine if there are differences in the activity of 17beta-hydroxysteroid dehydrogenase and 5alpha-reductase (responsible for the production of testosterone and dihydrotestosterone, respectively) in sebaceous glands obtained from men and women with and without acne. DESIGN: Single-center examination of androgen levels and sebaceous gland enzyme activity in a cohort of volunteers. SETTING: Academic referral center. PATIENTS: Thirty-four subjects, consisting of 8 women with acne, 10 women without acne, 8 men with acne, and 8 men without acne. INTERVENTIONS: Single visit for blood sampling and 2 biopsies of forehead skin. MAIN OUTCOME MEASURES: Serum levels of androgens were determined and compared with the activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase in sebaceous glands microdissected from skin samples. RESULTS: No significant differences in the activity of 5alpha-reductase or 17beta-hydroxysteroid dehydrogenase in sebaceous glands according to the presence of acne were noted in either men or women. The activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase was significantly greater in sebaceous glands from men (n = 16) than women (n = 17). The oxidative activity of 17beta-hydroxysteroid dehydrogenase was 2-fold higher in men than women. Serum levels of dehydroepiandrosterone sulfate, androstenedione, testosterone, and dihydrotestosterone were significantly higher in women with acne than in women without acne. No differences in serum androgen levels were noted in men on the basis of the presence of acne. CONCLUSIONS: Higher serum androgen levels are associated with the presence of acne in women. A role for locally produced androgens in this process, however, cannot be excluded.