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Heterotopic sebaceous glands in the esophagus: histopathological and immunohistochemical study of a resected esophagus.

A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a congenital anomaly. The present case concerns a 79-year-old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions. Histological examination of these glands, all of which were located in the lamina propria, revealed lobules of cells that showed characteristic sebaceous differentiation. Bulbous nests of proliferating basal cells showing sebaceous differentiation were occasionally observed in the esophageal epithelium. Of the antibodies against six different keratins used, only anti-keratin 14 labeled both the heterotopic sebaceous glands and the bulbous nests. Acquired metaplastic change of the esophageal epithelium is probably the pathogenetic mechanism involved in these unusual lesions.

Aged↗

The hamster ear sebaceous glands. I. Examination of the regional variation by stripped skin planimetry.

A stripped skin planimetric method was developed to measure the ear sebaceous gland areas using a Numonics Graphics Calculator. The ear skin was manually separated from the cartilage and the area of the sebaceous gland units observed from the underside was determined. This procedure is less time-consuming than standard histologic techniques. Using stripped skin planimetry, it was demonstrated that the sebaceous gland size was greatest at the basal region of the ear and decreased toward the periphery. Regional variations in the density of the sebaceous gland units were also observed. In using the ear sebaceous model system it is important to standardize the site of biopsy in order to avoid sampling errors. The increase in ear sebaceous gland area from weaning to sexual maturity in the male hamster parallels the increase in flank organ area. This observation suggests that the ear and the flank organ sebaceous glands are comparable sebaceous models since they show a similarity in their response to the changing hormone levels during sexual maturation.

Animals↗

Regional differences of pheromone production in the sebaceous glands of castrated goats treated with testosterone.

The primer pheromone is responsible for the "male effects" in goats and produced in the sebaceous glands testosterone-dependently. In the present study, the responses of sebaceous glands obtained from the head and rump regions of castrated goats were examined by our bioassay system after testosterone treatment to demonstrate the presence of regional differences in the pheromone production in male goats. The testosterone treatment resulted in the marked development of sebaceous glands and the induction of pheromone bioactivity in the head region of the goats. On the contrary, this treatment brought neither development of the sebaceous glands nor induction of pheromone bioactivity in the rump region. The treatment increased immunoreactivities to androgen receptors (AR) and 5alpha-reductase in the sebaceous glands of both regions, although the activities were more apparent in the head region than the rump region. These findings suggest that the primer pheromone of male goats is produced specifically in the sebaceous glands of the head region due partly to regional differences in the expression of AR and 5alpha-reductase mediating testosterone bioactivities.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

delta 5-3 beta-hydroxysteroid dehydrogenase activity in sebaceous glands of scalp in male-pattern baldness.

Sebaceous glands were isolated by manual dissection using a stereomicroscope from skin specimens of bald scalp of men with male-pattern baldness undergoing hair transplant or scalp reduction surgery and also from specimens taken from hairy and bald areas of scalp at autopsy of adult male victims of accidental death within 3 h post mortem. Homogenates of the isolated glands exhibited activities of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 17 beta-hydroxysteroid dehydrogenase, and testosterone 5 alpha-reductase by the conversion of [3H]dehydroepiandrosterone (DHA) to 3H-delta 4-androstenedione (AD), [3H]testosterone, and [3H]dihydrotestosterone. Homogenates of glands from bald (B) scalp had greater 3 beta HSD activity than homogenates of glands from hairy (H) scalp. After differential centrifugation, 3 beta HSD activity was found mainly in the microsomal and 105,000 X g supernatant fractions. Specific activity of the enzyme based on protein mass was highest in the microsomal fraction; however, the total 3 beta HSD activity in the 105,000 X g supernatent of B glands was significantly (p less than .01) greater than that of H glands. 3 beta HSD activity in sebaceous glands isolated from autopsy specimens did not differ from that of glands isolated from surgical specimens in apparent Km (0.13-0.14 microM), pH optima (8.0), or coenzyme requirement for NAD. Since substantial 3 beta HSD activity was present in the cytosol, and cytosol of B glands showed increased 3 beta HSD activity, the increased conversion of DHA to AD may be a critical step for androgenic action and may be responsible for excessive androgenicity in male-pattern baldness.

3-Hydroxysteroid Dehydrogenases↗

Testosterone-dependent primer pheromone production in the sebaceous gland of male goat.

To test the hypothesis that the primer pheromone responsible for inducing the "male effect" is produced in the sebaceous gland androgen dependently, we examined the correlation between morphological changes of sebaceous glands and the pheromone activity in skin samples taken from castrated goats that had been treated with testosterone. Five castrated goats were implanted s.c. with testosterone capsules to maintain physiological levels of plasma testosterone for four weeks. Skin samples were obtained from the head region on Day 0 (the day of testosterone implant), Day 7, Day 14, Day 28 (the day of testosterone removal), Day 36, Day 42, and Day 56. Matched blood samples were also collected for measurement of testosterone concentration. The pheromone activity of the ether-extracts of the upper dermal layer containing sebaceous glands was assessed by its stimulatory effect on the hypothalamic GnRH pulse generator, which was monitored for changes of specific multiple unit activity (MUA) in ovariectomized estradiol-primed goats as described previously. The sebaceous gland enlarged during the testosterone treatment but reduced in size after testosterone removal. The pheromone activity first appeared in 2 out of 5 goats on Day 7 and in all the 5 goats by Day 28. Fourteen days after testosterone removal (Day 42), the pheromone activity was no longer detectable in any of the 5 goats. In short, the sebaceous gland size and the pheromone activity shifted almost in parallel. The present results provide strong support for the view that the primer pheromone is produced testosterone dependently in the sebaceous gland of the male goat.

Animals↗

Pathology of intraoral sebaceous glands.

Large clinical studies have shown that intraoral sebaceous glands are present in 70 to 95% of the population. In many individuals these small white to yellow macules and papules are so numerous that they dominate the buccal mucosa. Despite their prevalence, pathological changes of these glands are considered uncommon. This paper reviews the pathologic spectrum of intraoral sebaceous glands including Demodex infestation, cystic lesions, sebaceous hyperplasia and neoplastic lesions. New data is presented on the true sebaceous cyst and the second reported case of intraoral steatocystoma simplex is documented.

Humans↗

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.

Animals↗

The relationship between the vitro activity of 3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase in human sebaceous glands and their secretory activity in vivo.

3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (delta 5-3 beta-HSD) catalyzes an early step in the synthesis of testosterone from dehydroepiandrosterone (DHA). We compared enzyme activity in back skin biopsies with sebum excretion rate (SER) in 14 individuals. The rate of conversion of [7 alpha-3H]DHA into [3H]-4-androstene-3,17-dione was measured in cryostat sections of skin and compared with the sebaceous gland content of the same biopsies. Reaction rate was proportional to the volume of sebaceous gland tissue in the sections. Enzyme activity was absent from sections without histologically identifiable sebaceous gland tissue. This suggests that the delta 5-3 beta-HSD is localized in sebaceous glands. SER, measured by a modified photometric technique at the biopsy site, correlated highly with sebaceous gland volume and with the rate of conversion of DHA into androstenedione in the biopsy. For each biopsy, specific activity of delta 5-3 beta-HSD in sebaceous glands was calculated by dividing the rate of formation of [3H]-4-androstene-3,17-dione by sebaceous gland volume. Specific activity of delta 5-3 beta-HSD did not correlate significantly with SER, suggesting that variations in concentration of delta 5-3 beta-HSD in sebaceous glands probably do not underlie variations in sebaceous gland activity.

3-Hydroxysteroid Dehydrogenases↗

Stereographic and stereometric study of sebaceous gland hyperplasia in rabbit pinnas induced by topically applied substances.

Tetradecane (TD), testosterone (TS), and dimethyl sulfoxide (DMSO) were separately inuncted on rabbit pinnas once a day; the pinnas were biopsied on days 1, 3, 7, and 28. Untreated pinnas and squalane-treated pinnas were used as controls. Three-dimensional images of sebaceous glands were reconstructed from their serial histologic sections using a computer-image analysis system. By stereometry, the sebaceous gland volumes gradually increased during the course of treatments with TS and DMSO, whereas the volumes of TD-treated sebaceous glands increased, reached the maximum on day 7, and then decreased. The acinus number was increased by all the substances, the DMSO-treated sebaceous glands on day 28 showing the largest number of acini. The volumes of individual acini increased until day 28 with TS treatment, whereas with TD and DMSO treatments they increased, reached the maximum on day 7, and then decreased. Stereographically, each untreated control sebaceous gland was composed of 20-30 pear-shaped acini. On day 28, acini of TS-treated sebaceous glands were swollen and ovoid in shape, DMSO-treated sebaceous glands resembled a bunch of grapes, and acini of TD-treated sebaceous glands were widely scattered and showed globular swelling arising from an elongated tube. Hyperplastic responses of sebaceous glands are quite different according to substances applied topically.

Administration, Topical↗

Sebaceous gland and sweat gland carcinomas of the skin. Clinicopathological study and significance of c-erbB-2 oncoprotein expression.

Thirteen sebaceous gland carcinomas and 10 sweat gland carcinomas were examined to elucidate any important histological parameters influencing their prognosis, and the relationship between immunohistochemical expressions of c-erbB-2 oncoprotein and survival of the patients was analyzed. Sebaceous gland carcinomas with vacuolated cytoplasm in more than 50% of whole tumor area, with necrosis, and without lymphoid cell infiltration in tumor nests and stroma had a higher incidence of tumor recurrence and tumor-related death than tumors with vacuolated cytoplasm in 50% or less of whole tumor area (p < 0.01), without necrosis, and with lymphoid cell infiltration in tumor nest and stroma (p < 0.05). Sweat gland carcinomas of all cases with fatal outcomes demonstrated tubular differentiation in 20% or less of whole tumor area, lymphatic permeation and desmoplastic reaction. Three sebaceous gland carcinomas and three sweat gland carcinomas were positive for c-erbB-2 oncoprotein. Two of three sebaceous gland carcinomas, and all three sweat gland carcinomas developed tumor recurrence and ended in tumor-related deaths. Sweat gland carcinomas with c-erbB-2 expression had significantly shorter survival than those with negative immunostain (p < 0.01). Cytoplasmic appearance, tumor necrosis, and lymphoid cell infiltration in tumor nests and stroma of sebaceous gland carcinoma, and tubular differentiation, lymphatic permeation, and growth patterns of sweat gland carcinoma are considered to closely correlate to the prognosis. Immunohistochemically detected c-erbB-2 oncoprotein may be an indicator of bad prognosis.

Adolescent↗

Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion.

PURPOSE: To evaluate the clinical findings, histopathologic features, methods of management, and outcomes in 25 patients with eyelid sebaceous gland carcinoma with and without conjunctival intraepithelial (pagetoid) invasion. PARTICIPANTS: Twenty-five patients with sebaceous gland carcinoma of the periocular region. DESIGN: Retrospective, observational case series. METHODS: The patients were divided into two groups: group A included those with sebaceous gland carcinoma with conjunctival intraepithelial (pagetoid) invasion, and group B included those with sebaceous gland carcinoma without conjunctival intraepithelial invasion. The demographic, clinical, and histopathologic features of sebaceous gland carcinoma were reviewed separately for each group. Ocular management results and systemic prognosis were reviewed. RESULTS: Of the 25 patients, 18 (72%) were females and 7 (28%) were males. The mean age at diagnosis was 65 years (range, 17-90 years). There were 11 patients (44%) in group A, and 14 (56%) in group B. The most common symptom in group A was ocular irritation (45%), and in group B the most common symptom was eyelid lump (86%). The most common sign in group A was diffuse eyelid thickening (72%), and in group B the most common sign was a distinct eyelid mass (43%). Six patients (55%) in group A, compared with one patient (7%) in group B, had both upper and lower eyelid involvement. The most frequent location of tumor epicenter was the outer third of the eyelid in both groups: 37% in group A and 57% in group B. Histopathologic origin of tumor was multicentric in four patients (36%) of group A and six patients (50%) of group B. Before referral, local recurrence had been found in 4 of 12 patients (33%) who underwent surgical treatment elsewhere. After referral, local recurrence was detected in 1 patient (9%) in group A and in 2 patients (14%) in group B. Orbital exenteration was necessary in 4 patients (36%) in group A and in one patient (7%) in group B. Tumor-related metastases occurred in two patients (18%) in group A and in two patients (14%) in group B. CONCLUSIONS: Sebaceous gland carcinoma with conjunctival intraepithelial (pagetoid) invasion has different clinical features compared with that without pagetoid invasion. Conjunctival intraepithelial (pagetoid) invasion carries a higher risk for orbital exenteration, but the risk of tumor-related metastases is similar in both groups.

Adolescent↗

The lipid composition of sebaceous glands as a reflection of gland size.

Following 4 h incubation in vitro, the patterns of incorporation of [I-14C] acetate into the lipid classes of human sebaceous glands which were dissected from small skin biopsies have been established for glands of different size. It has been shown that in the larger sebaceous glands proportionately more of the labelled acetate is incorporated into squalene at the expense of triglycerides. Experiments are presented as a result of which we conclude that this in vitro phenomenon, observed with [I-14C] acetate incorporation, does reflect parallel changes in the proportions of these lipids actually present in glands of different size. It is suggested that the larger sebaceous glands of the acne patient elaborate sebum which has an enhanced potential for inducing comedo formation by virtue of an increased concentration of squalene. This work also demonstrates that, in the interpretation of in vitro studies of sebaceous gland lipogenesis utilizing labelled precursors, the size of the sebaceous glands must be carefully considered whenever patterns of incorporation are being compared.

Acne Vulgaris↗

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

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 micrograms 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 microgram) 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.

Animals↗

Analysis of lipid composition of isolated human sebaceous gland homogenates after incubation with cutaneous bacteria. Thin-layer chromatography.

The effects of specific species of skin bacteria on human sebaceous gland lipids in vitro were analyzed. Isolated dissected sebaceous glands were pooled, homogenized, and sterilized, then incorporated into peptone-yeast extract medium and used as substrate for growth of Propionibacterium acnes, P. granulosum, and Staphylococcus epidermidis subgroup II. The sebaceous lipids were analyzed by thin-layer chromatography before and after bacterial growth. The most striking effect of bacteria on sebaceous gland lipid composition was the hydrolysis of sebaceous triglycerides. The degree of hydrolysis varied with bacterial strain but was most complete with P. acnes and P. granulosum. Staphylococci were not effective in hydrolyzing sebaceous triglycerides at pH 4.5 although, when the pH of the medium was raised to pH 6.4, some strains of staphylococci were as effective as the propionibacteria in hydrolyzing sebaceous triglycerides to free fatty acids. Thus minor changes in acidity may play asignificant role in controlling the lipolytic activity of staphylococci on skin. Another effect of bacterial action on sebaceous gland lipids was the esterification of sebaceous cholesterol to cholesteryl esters. Thus, bacterial action must be taken into account in evaluating studies of alterations in cutaneous cholesterol and cholesteryl esters in skin surface lipids in normal and disease states.

Bacteriological Techniques↗

Treatment of sebaceous gland hyperplasia with the pulsed dye laser.

BACKGROUND AND OBJECTIVE: Sebaceous gland hyperplasia may be treated by cryotherapy, cauterization, topical chemicals, or excision. The major disadvantage of these therapeutic strategies is a considerable risk of postoperative scarring or dyspigmentation. The pulsed dye laser may be an effective and safe alternative treatment option. STUDY DESIGN AND METHODS: Our report presents two patients with sebaceous gland hyperplasia who were treated with the pulsed dye-laser (585 nm, 6.5-8 J/cm2, 300-450/microsecond). RESULTS: After 2-3 treatment sessions, the lesions were completely gone. To data, no side effects have been observed. CONCLUSIONS: Based upon our experiences, we recommend the pulsed dye laser as a safe, fast, and minimal straining treatment alternative for hyperplasia of sebaceous glands.

Female↗

Lipogenesis in isolated human sebaceous glands.

Lipogenesis in isolated human sebaceous glands from [U-14C]glucose, [U-14C]leucine, [U-14C]isoleucine, and [U-14C]valine has been determined by thin-layer chromatography. Total lipogenesis from 2 mmol/l [U-14C]glucose was 114.8 +/- 22.3 pmol/gland per h (mean +/- SE), with 53.8% being incorporated into triglycerides, 20.2% into squalene, 12.8% into phospholipids, 2.1% into cholesterol and 7.1% into wax monoester and cholesterol ester and 5% into di- and monoglycerides and free fatty acids. Total lipogenesis from 2 mmol/l [U-14C]leucine, 2 mmol/l [U-14C]isoleucine, and 2 mmol/l [U-14C]valine in the presence of 2 mmol/l glucose was 26, 29 and 9%, respectively, of that seen with 2 mmol/l glucose alone. The pattern of 14C distribution in the various lipid classes from the three U-14C-labelled branched-chain amino acids was not significantly different from that seen with [U-14C]glucose.

Carbon Radioisotopes↗

Culture of cells derived from the human sebaceous gland under serum-free conditions without a biological feeder layer or specific matrices.

We succeeded in serially culturing cells derived from human sebaceous gland (sebocytes) under serum-free conditions. Sebaceous glands were isolated from dispase-treated facial skin specimens and cultured using two different methods, explant culture and dispersed cell culture, in KGM. In both types of culture the sebocytes proliferated rapidly without a biological feeder layer or specific matrices. It was possible to cultivate the cells serially for at least three passages (explant culture) and six passages (dispersed cell culture), and to store the cells in liquid nitrogen with good recovery. Analytical thin-layer chromatography revealed that the cells synthesized a large amount of sebum-specific lipids, squalene and wax esters in vitro. Both testosterone and 5 alpha-dihydrotestosterone significantly stimulated the proliferation of the sebocytes. The methods presented here may permit a large series of studies on the function of sebaceous glands or cells derived from sebaceous glands.

Cell Culture Techniques↗

Sebaceous-gland deposition of isotretinoin after topical application: an in vitro study using human facial skin.

As yet, topically applied isotretinoin fails to show convincing clinical efficacy in the treatment of severe recalcitrant acne. Although the reason for this is not known, it is possible that topical application results in low, pharmacologically inactive isotretinoin concentrations in the sebaceous glands, the most likely site of isotretinoin action. It has been suggested that topically applied liposomes enhance the delivery of drugs into the sebaceous glands. Accordingly, we compared the isotretinoin concentration in sebaceous glands and other skin compartments following topical application of small unilamellar vesicles, multilamellar vesicles, preformed vesicles (Natipide II) or mixed micelles of lecithin and bile salt. We found that the concentration of isotretinoin measured in the sebaceous glands varied between 0.17 and 1.57 ng/mg tissue. The comparison between ethanolic gel and liposomal or micellar gel did not reveal any significant difference. However, application of the Natipide formulation resulted in significantly lower isotretinoin concentrations in the sebaceous glands when compared to the ethanolic gel. Autoradiography and fluorescence microscopy indicated that isotretinoin penetrated the sebaceous glands along the follicular route. In conclusion, our in vitro study showed that, following topical administration, substantial amounts of isotretinoin were delivered to the sebaceous glands via the follicular route, whereby the ethanolic gel was as efficient as a liposomal or a mixed micellar gel.

Administration, Topical↗