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

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-R1/CRH-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 beta- hydroxysteroid dehydrogenase/Delta(5-4) isomerase, although it did not affect cell viability, cell proliferation, or IL-1 beta-induced IL-8 release. CRH, dehydroepiandrosterone, and 17 beta-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.

3-Hydroxysteroid Dehydrogenases↗

The isolation and characterization of androgen-dependent genes in the flank organs of golden Syrian hamsters.

To elucidate the molecular action of androgens, we have isolated two androgen-dependent genes, FAR-17a and -17c, from the cDNA library of flank organs of male golden Syrian hamsters by a differential hybridization method. FAR-17a has been reported previously. Androgens regulated the expression in the flank organs, ear lobe and skin. FAR-17a protein was located in sebaceous glands. FAR-17c has a similar expression pattern to that of FAR-17a, but its response to androgen is faster than that of FAR-17a. It is expressed strongly in the liver, sebaceous glands and brain. The homology search and mRNA expression pattern suggested that it might encode a stearyl CoA desaturase (SCD) of golden Syrian hamsters. The SCD is a key enzyme in fatty acid biosynthesis and its expression is controlled by temperature, nutritional conditions and hormones. This is the first report that the mRNA expression of stearyl CoA is regulated by androgens.

Amino Acid Sequence↗

Biological purpose of acne.

It is argued that the close endocrine control of human sebaceous glands and the likely effects of acne on selection indicate that both gland and disease have persisted because they are biologically useful. Two possibilities are proposed: sebum may provide precursor substrates for metabolism and synthesis by the epidermis of compounds of both local and systemic importance; and the adjuvent properties of corynebacteria which colonise the active sebaceous glands of acne may facilitate certain general immunological membrane.

Acne Vulgaris↗

Acne: current concepts of pathogenesis and approach to rational treatment.

Acne is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and young adulthood. The pathogenesis involves abnormal follicular hyperkeratosis and obstruction of the follicle, stimulation of sebaceous gland secretion by androgens, and proliferation of Propionibacterium acnes, which promotes inflammation. Treatment regimens should be designed based upon an understanding of the multifactorial basis of pathogenesis. Both topical and systemic agents may be employed to normalize keratinization, decrease sebaceous gland activity, decrease the follicular P. acnes population, and minimize inflammation.

Acne Vulgaris↗

Accordion-like structure of terminal hair follicles of the human scalp.

Terminal hair follicles extracted after ethylenediaminetetraacetic acid treatment preserved the basal cell surface of the outer root sheath well enough to examine the outer surface in detail. Light microscopic observations of whole mount specimens revealed several sawtooth-like structures of follicular epithelium in the lower portion of terminal hair follicle. Vertical sections of the human scalp also showed several invaginations of the outer root sheath of terminal hair follicles in the lower portion, not in association with the arrector pili muscle. Scanning electron microscopy of the same specimens demonstrated accordion-like structures below the sebaceous gland in the lower half of anagen terminal hair follicles and surrounding the entire circumference of the follicles. Sawtooth-like structures were unilaterally observed at the level of the middle or lower portion below the sebaceous gland. With transmission electron microscopy, these structures were seen as undulations of basal cells which preserved hemidesmosomes, although the basal lamina had been peeled off during the extraction procedure. Thus, this accordion-like structure is a genuine structural variation of some human anagen hair follicles and not an artifact.

Basement Membrane↗

The skin of primates. XLII. The skin of the silvered sakiwinki (Pithecia monachus).

The following characteristics indicate that the skin of the silvered sakiwinki (Pithecia monachus, E. Geoffroy, 1812) is not only basically similar to other primitive cebids, but also remarkably close to that of callithricids: a thin epidermis with diminished monoamine oxidase activity; a poorly-developed dermis, paucity of elastic fibers, and scant adnexal blood supply; hair follicles arranged in linear perfect sets; grouped hairs present on the cheek; an absence of glycogen and phosphorylase in most sebaceous glands; apocrine glands present throughout most haired body regions, but totally absent from the dorsum; and poorly-differentiated eccrine glands, confined to volar friction surfaces, which are characterized by unusual glycolytic properties. Other noteworthy cutaneous traits include: concomitant epidermal and dermal pigmentation in the face and scalp; Merkel-like disks in the friction surfaces; moderately well-developed Haarscheibe, associated with large, dorsal guard hairs; small, discrete sebaceous glands throughout the dorsum; a 1:1 ratio of apocrine glands to hair follicles in the facial, gular and anogenital areas; and numerous cholinesterase-reactive nerves around eccrine but not apocrine secretory coils. Although previous comparative studies on the skin of New World monkeys suggest that the systematic designation of two familial taxa is warranted, information regarding five of the fifteen genera which comprise the families Callithricidae and Cebidae is totally lacking. Given that three of these genera (Leontopithecus, Chiropotes and Brachyteles) can no longer be obtained from animal dealers because of exportation laws, the authors were fortunate to acquire representatives of the remaining two genera: Callicebus (titi monkeys) and Pithecia (sakiwinkis). Besides defining cutaneous characteristics common to specific taxa, two earlier works by Hanson and Montagna ('62) and Perkins et al, ('68) also suggested that members of the cebid subfamilies Aotinae and Pitheciinae possess cutaneous traits that bridge an interesting gap with the callithricids. Therefore, the acquisition of these two additional aotine and pithecine genera provided the opportunity to test this hypothesis. The following, therefore, is not just another detailed manuscript regarding the skin of primates. Rather, it is an effort to define the integumental characteristics of the last obtainable New World monkey genera, and to assess those cutaneous signatures which are interfamilially common to both the callithricids and more primitive cebids. Primary emphasis is placed on the genus Pithecia; pertinent findings concerning Callicebus will be incorporated into the forthcoming and final summarization of the phylogenetic significance of the skin of New World monkeys (Perkins, '75).

Acetylcholinesterase↗

Morphological, histochemical and immunohistochemical characterization of secretory production of the ciliary glands in the porcine eyelid.

In addition to performing general histology and cytology of the ciliary glands of the miniature pig, we studied the localization of glycoconjugates and beta-defensins in these glands with the use of carbohydrate histochemical and immunohistochemical methods. The secretory cells of the glands were equipped with non-homogeneous secretory granules, a well-developed Golgi apparatus and rough endoplasmic reticulum. The secretory epithelium and luminal secretion of the glands contained large amounts of neutral and acidic glycoconjugates with various saccharide residues (alpha-L-Fuc, beta-D-Gal, alpha-D-GalNAc and sialic acid). The sebaceous glands and tarsal glands also exhibited positive reactions to most of the histochemical methods. Additionally, the antimicrobial peptide group of beta-defensins was demonstrated to be products of the ciliary glands, as well as the sebaceous glands and tarsal glands. The results obtained are discussed with regard to the specific function of the ciliary glandular secretions. These secretory products may be related to the moistening and general protection of the skin surface of the eyelid and ocular surface.

Animals↗

Morphology of the interdigital glands of a Formosan serow (Capricornis crispus swinhoei).

The morphology of the interdigital glands of a male 9-year-old Formosan serow was examined. The glands were sock-shaped depression of the skin and were present in four feet. The glands were composed of a neck and a body. The epidermis of inner wall of the glands was keratinized stratified squamous epithelium. Apocrine glands were developed, while the sebaceous glands and hair follicles were very poorly developed. Contents, probably dirt, were small in the interdigital glands. These findings resemble to the interdigital glands of the Japanese serow and suggest that the interdigital glands have very low activity of secretion.

Animals↗

Lack of gonadal control of the dorsal gland and sandbathing in male and female bannertail kangaroo rats, (Dipodomys spectabilis).

Previous studies have demonstrated gonadal control of mammalian scent glands; castration leads to reduced scent-marking rates and smaller gland sizes. I investigated whether gonadal hormones control the size of the dorsal gland (a specialized sebaceous gland) and sandbathing as a scent-marking behavior in adult male and female bannertail kangaroo rats (Dipodomys spectabilis). Gland sizes of males and females were similar in all age classes, except adult males with larger body weights had proportionately larger glands than females. Male gland sizes declined 18% following castration but were not significantly smaller than those of intact males; females showed no change in dorsal gland size either as a result of ovariectomy or after estradiol benzoate implants. Sandbathing rates also did not decline as a result of gonadectomy. Rather, castrated males and overiectomized females sandbathed at higher frequencies than intact males and ovariectomized females with estradiol benzoate implants, respectively. Gonadal hormones apparently have little influence on the function of a specialized scent gland and may inhibit sandbathing as a scent-marking behavior in adult D. spectabilis.

Animals↗

Morphogenesis of fingers and branched organs: how collagen and fibroblasts break the symmetry of growing biological tissue.

Understanding the growth of branching organs is an important scientific endeavour. It has crucial applications, from saving premature newborns, to repairing or even regenerating organs. Despite differences in timing and shape, branching morphogenesis of all branching organs or glands (lung, kidney, salivary, lachrymal, mammary glands, sebaceous and sweat glands, prostate, guts papillae etc.) is similar: an epithelial sheet of cells, forming a 2D layer, penetrates into a 3D mass of mesenchymal cells. Inside the epithelium, a lumen is filled with fluid. As the epithelium grows, it evolves into a branched structure. The pattern of branches is in some cases stereotypic, deterministic, and it has memory effects. We present a simple line of reasoning that predicts that viscous fingering of biological tissue will exhibit all of these features. The line of reasoning is based on the idea that surface tension selects the shape of a growing branch, as is well known in the context of moving boundary problems, except that in this case, the surface is akin to a liquid-crystal. The anisotropy of the surface tension comes from a symmetry breaking by collagen and fibroblasts. The equilibrium shape of the corresponding boundary is that of an actual fingertip, and the out-of-equilibrium shape is that of branched organs, such as the lung.

Animals↗

The role of androgen receptors in the clinical course of nevus sebaceus of Jadassohn.

Nevus sebaceus of Jadassohn (NSJ) is a benign, congenital hamartoma that often presents at birth, appears to regress in childhood, and grows during puberty, suggesting possible hormonal control. We studied 18 cases of NSJ from children and adults for immunohistochemical evidence of androgen receptor expression. The lesions were evaluated for location and pattern of immunostaining, and these findings were compared between age groups, sexes, and to androgen receptor expression in normal skin. Androgen receptor positivity was seen in the sebaceous glands, in eccrine glands with and without apocrine change, and rarely in keratinocytes in the sebaceous nevi. There were no significant differences in staining location or pattern between the age groups or sexes. Normal skin showed similar staining in the sebaceous glands but did not show staining of the eccrine glands or keratinocytes. Androgen receptors are present in all epithelial components of NSJ, but there is no change in androgen receptor expression during puberty.

Adolescent↗

[Bilateral nevus of the caruncle].

BACKGROUND: Pathologic processes of the caruncle are relatively rare with a predominance of papillomas, pyogenic granulomas and nevi. PATIENT: A 22 year old Caucasian male patient presented with bilateral hyperpigmentations of the caruncle. They had first been observed at an age of seven and showed slight progression in size and colour with time. Examination revealed hyperpigmentation with clear pseudocystic spaces. The tarsal or bulbar conjunctiva was not involved. An excision of both processes was performed. HISTOLOGY: Light microscopy revealed nests of nevus cells with melanin granules and round basophilic nuclei as well as gland ducts and sebaceous glands, beneath and within the multilayered keratinizing and nonkeratinizing squamous epithelium. The sections revealed a bilateral melanocytic compound nevus of the caruncle. DISCUSSION: To our knowledge, there is no report on bilateral nevi of the caruncle among the Caucasian population. The possibility of a common precursor cell during the embryologic development causing the bilaterality is discussed.

Adult↗

Mammalian wax biosynthesis. I. Identification of two fatty acyl-Coenzyme A reductases with different substrate specificities and tissue distributions.

The conversion of fatty acids to fatty alcohols is required for the synthesis of wax monoesters and ether lipids. The mammalian enzymes that synthesize fatty alcohols have not been identified. Here, an in silico approach was used to discern two putative reductase enzymes designated FAR1 and FAR2. Expression studies in intact cells showed that FAR1 and FAR2 cDNAs encoded isozymes that reduced fatty acids to fatty alcohols. Fatty acyl-CoA esters were the substrate of FAR1, and the enzyme required NADPH as a cofactor. FAR1 preferred saturated and unsaturated fatty acids of 16 or 18 carbons as substrates, whereas FAR2 preferred saturated fatty acids of 16 or 18 carbons. Confocal light microscopy indicated that FAR1 and FAR2 were localized in the peroxisome. The FAR1 mRNA was detected in many mouse tissues with the highest level found in the preputial gland, a modified sebaceous gland. The FAR2 mRNA was more restricted in distribution and most abundant in the eyelid, which contains wax-laden meibomian glands. Both FAR mRNAs were present in the brain, a tissue rich in ether lipids. The data suggest that fatty alcohol synthesis in mammals is accomplished by two fatty acyl-CoA reductase isozymes that are expressed at high levels in tissues known to synthesize wax monoesters and ether lipids.

Aldehyde Oxidoreductases↗

CD36/fatty acid translocase in rats: distribution, isolation from hepatocytes, and comparison with the scavenger receptor SR-B1.

The new mAb UA009 recognizes an antigen expressed by microvascular endothelium, by lymphatic endothelium, and by some epithelia in a number of organs, including the small intestine, lactating mammary gland, kidney, lung, sebaceous glands, and circumvallate papillae of the tongue. This antigen is also expressed abundantly in the splenic red pulp and marginal zone and by monocytes, macrophages, and erythrocytes (but not by platelets). Among tissues that store or metabolize fatty acids, the antigen is expressed by adipocytes, cardiomyocytes, and red skeletal muscle. Importantly, it is expressed by steroidogenic cells in the adrenal gland, testis, and ovary, whereas in the liver it is expressed by hepatocytes in a pattern that is dependent on gender and genetic background. mAb UA009 immunoprecipitated a mol wt 85-kDa surface protein from detergent extracts of hepatocytes from Dark Agouti female rats. The N-terminal amino acid sequence of this protein was identical to fatty acid translocase (FAT), the rat cluster of differentiation 36 (CD36) ortholog. The mAb also reacted with COS-7 cells transfected with cDNA encoding FAT. cDNAs encoding a CD36/FAT-like polypeptide were prepared from both liver and heart RNA by RT-PCR. The nucleotide sequences obtained from these cDNAs (Dark Agouti rats) revealed identity and 99% similarity, respectively, with the published sequences of Cd36/Fat in rats of the Wistar and Sprague-Dawley strains. The absence of the UA009 antigen in CD36/FAT-deficient SHR/N rats confirmed the identity of the UA009 antigen and CD36/FAT. We suggest that CD36/FAT might function in the liver as a sex-regulated accessory molecule, either in reverse cholesterol transport and/or in fatty acid uptake.

Animals↗

Adnexal polyp of neonatal skin.

The adnexal polyp of neonatal skin is a small, usually solitary tumour of the skin occurring mostly on the areola of the nipple of the neonate. Our statistics reveal an incidence of 4-0% in 3,257 newborn infants. Histologically it always contains hair follicles, eccrine glands and vestigial sebaceous glands, hence the term 'adnexal polyp of neonatal skin' is proposed. No similar report has been hitherto recorded.

Adnexal Diseases↗

Expression pattern of the bullous pemphigoid-180 antigen in normal and neoplastic epithelia.

BP180 is a 180kDa hemidesmosomal protein recognized by bullous pemphigoid (BP) and pemphigoid gestationis (PG) autoantibodies. Recent cloning and sequence analysis performed by our laboratory have revealed that BP180 is a transmembrane protein with a long extracellular collagen-like region. A rabbit polyclonal antibody has been generated against a recombinant protein, designated GST-N delta 1, containing a segment of the BP180 ectodomain. The resulting antiserum, RN delta 1A, was shown to specifically react with BP180 on immunoblot, and labelled the extracellular region of the epidermal hemidesmosome on immunoelectron microscopy. A panel of normal and neoplastic human tissues were analysed by indirect immunofluorescence (IF) and RN delta 1A, to determine the distribution of BP180. A total of nine basal cell carcinomas (BCCs) and four squamous cell carcinomas (SCCs) of the skin were also studied. Intense IF staining was seen along the basement membrane zone (BMZ) of the epidermis, hair follicles, and the periphery of sebaceous gland lobules. The sebaceous lobules showed more intense staining in areas close to the duct. The epithelial BMZ of the following tissues also reacted with RN delta 1A: cornea, ocular conjunctiva, buccal mucosa, upper oesophagus, placenta (amnion placentum), umbilical cord and transitional epithelium of the bladder. The epithelium of the jejunum and ovary failed to react with RN delta 1A. Staining of the BCCs and SCCs was variable. Five of six nodular BCCs showed some anti-BP180 staining at the tumour-stromal interface, although the level of staining was less intense than that observed in the overlying normal epidermis. All three morphoeic BCCs analysed in this investigation did not show any staining with RN delta 1A. Three of four SCCs showed weak staining at the tumour-stromal interface. Thus, the tissue distribution of BP180 paralleled that of hemidesmosomes, and expression of this protein was found to be decreased or absent in cutaneous neoplasms.

Autoantigens↗

The use of high-energy electrons to depilate the breech of sheep.

The use of high-energy electrons for permanently depilating areas of sheep skin was evaluated. The most effective dose of electrons for depilation was 17.5Gy. Histological changes in skin treated at this dose were examined in one sheep over 18 months and in 5 sheep over 89 d. Effects of treatment on bodyweight gains and fleece growth were examined by comparing the productivity of a further 5 sheep treated on the breech with high-energy electrons, with that of conventionally mulesed sheep (n = 5) and untreated controls (n = 5). Electron treatment resulted in immediate death of cells in the germinative region of the wool follicle bulbs. Within 10 d of treatment the treated areas were completely depilated. Wool follicle shafts in the treated areas regressed rapidly towards the epidermis and remained quiescent for the whole trial (89 d). A sheep treated 18 months previously has remained largely depilated, although a few sparse fibres are present. Epidermal acanthosis and orthokeratosis were present at 26 d after treatment. The thickened stratum corneum then sloughed off, but the epidermis remained acanthotic for the entire trial. Sweat glands and most sebaceous glands were destroyed by the treatment and were replaced by fibrotic, avascular tissue in the dermis. In all other respects the external appearance of the electron-treated breech was similar to that of mulesed sheep. There were no apparent side-effects of treatment. Neither mulesing nor electron treatment altered weight gains or fleece growth rates.

Animals↗

[The influence of heat-induced epitope retrieval on endogenous avidin-binding activity (EABA) and blocking of EABA in immunohistochemistry].

OBJECTIVE: To study the influence of heat-induced epitope retrieval (HIER) on endogenous avidin-binding activity (EABA) and to establish an effective way to block EABA in immunohistochemistry. METHODS: Systematically screening EABA in 164 (679 samples) formalin-fixed and paraffin-embedded human tissues including 76 (102 samples) normal tissues and 88 (577 samples) tumor tissues as well as 4 (80 samples) formalin-fixed and paraffin-embedded rat normal tissues using tissue array (tissue chip), HIER, immunohistochemistry and egg white solution blocking. In addition, EABA was also examined in 9 (15 samples) human frozen tissues. RESULTS: (1) EABA was detected in frozen tissues. (2) No staining for EABA was seen in formalin-fixed and paraffin-embedded tissues. (3) EABA was revealed after the tissues treated with microwave HIER. (4) The density of signal for EABA was variable from tissue to tissue and cell to cell. (5) The signals of EABA expressed in scatter or diffuse in tissues and in granular form in cytoplasm. (6) EABA was found in a wide range of epithelial tissues, especially in gland epithelia of normal and tumor tissues. These included kidney, adrenal cortex, liver, C cells of thyroid gland, oxyphil cells of parathyroid, fundal gland of stomach, sebaceous gland of skin, duct of salivary; oncocytoma and papillary adenocarcinoma of kidney and thyroid gland, adenolymphoma of parotid, carcinoma of liver cell, adenocarcinoma of stomach, colon, prostate, gall bladder and endometrium, and so on. (7) EABA was easier revealed by higher pH value buffer (EGTA pH 9.0) than that with lower pH value (EDTA pH 8.0 and citrate pH 6.0). (8) The revealed EABA could be effectively blocked using 20% egg white solution. CONCLUSIONS: HIER could unmask EABA in formalin-fixed and paraffin-embedded tissues. The unmasked EABA present in a wide range of human normal and tumor tissues as well as in rat normal tissues. The EABA could influence routine immunohistochemistry staining when using (strept)avidin-horseradish peroxidase detective system. The egg white solution could effectively block EABA and eliminate the influence of EABA on immunohistochemistry.

Animals↗