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The expression of soluble N-ethyl-maleimide sensitive fusion attachment protein receptor (SNARE) proteins in apocrine glands has not been fully elucidated. In addition to performing ultrastructural observation of the ceruminous glands in goats, our study focuses on the demonstration of β-defensins, SNARE proteins and Rab3D in these glands with the use of immunohistochemical methods. The secretory cells were equipped with two types of vesicles, Golgi apparatus and abundant rough endoplasmic reticulum (ER). Additionally, in some of them, the characteristic concentric structures composed of rough ER were observed in their circum- and infranuclear parts. The expression of phosphorylated inositol requiring enzyme 1a was also detected. These findings may indicate their ability to produce numerous secretory proteins and the maintenance of homeostasis in the glandular cells. Furthermore, β-defensins were demonstrated as products of the ceruminous glands. The present investigation also revealed the presence of SNARE proteins and Rab3D. It is suggested that these proteins are concerned with the secretory machinery of this gland type.

Ultrastructural differences are shown between the caecal organization in three blood-feeding polyopisthocotylean monogeneans, i.e., the chimaericolid Chimaericola leptogaster from the holocephalan Chimaera monstrosa and two hexabothriids, Callorhynchocotyle callorhynchi from the holocephalan Callorhynchus capensis and Rajonchocotyle emarginata from the elasmobranch Amblyraja radiata. In C. leptogaster, digestive cells and connecting syncytium, joined close to the luminal surface by septate junctions, are arranged alternately along the caecal epithelial wall; the nuclear regions of both cell types are sunk below the general level of the caecal epithelium; a concave depression on the apical margin of the digestive cells bears lamellae; and this depression is covered by a lamellate bubble formed by thin projections emanating from the connecting syncytium. The luminal surface of the connecting syncytium is covered with outgrowths terminating in the form of long, narrow processes. In R. emarginata and C. callorhynchi, the predominant digestive cells are at different stages of development and occur in groups, developing digestive cells bulge into the caecal lumen from the connecting syncytium with contact sites present close to the luminal surface, and the luminal surface structures of both the connecting syncytium and the digestive cells are short lamellae. In these two hexabothriids, a holocrine (or apocrine) process for the elimination of digestive product is assumed via the detachment of fully differentiated, bulging digestive cells. Free, apparently sloughed digestive cells and residual bodies are present within the caecal lumen, and replacement digestive cells are numerous in the connecting syncytium. In the chimaericolid, free bubbles containing residual bodies and portions of digestive cells filled with degenerating digestive vesicles occur in the caecal lumen along with large amounts of male and female reproductive material. The usefulness of characteristics of the caecal ultrastructure as taxonomic traits at the family level is discussed.

In contrast to the well defined mechanism of merocrine exocytosis, the mechanism of apocrine secretion, which was first described over 180 years ago, remains relatively uncharacterized. We identified apocrine secretory activity in the late prepupal salivary glands of Drosophila melanogaster just prior to the execution of programmed cell death (PCD). The excellent genetic tools available in Drosophila provide an opportunity to dissect for the first time the molecular and mechanistic aspects of this process. A prerequisite for such an analysis is to have pivotal immunohistochemical, ultrastructural, biochemical and proteomic data that fully characterize the process. Here we present data showing that the Drosophila salivary glands release all kinds of cellular proteins by an apocrine mechanism including cytoskeletal, cytosolic, mitochondrial, nuclear and nucleolar components. Surprisingly, the apocrine release of these proteins displays a temporal pattern with the sequential release of some proteins (e.g. transcription factor BR-C, tumor suppressor p127, cytoskeletal β-tubulin, non-muscle myosin) earlier than others (e.g. filamentous actin, nuclear lamin, mitochondrial pyruvate dehydrogenase). Although the apocrine release of proteins takes place just prior to the execution of an apoptotic program, the nuclear DNA is never released. Western blotting indicates that the secreted proteins remain undegraded in the lumen. Following apocrine secretion, the salivary gland cells remain quite vital, as they retain highly active transcriptional and protein synthetic activity.

Functional ultrastructure and its phylogenic implications in the bothriocephalid cestode Eubothrium salvelini (Schrank, 1790) are described and discussed. The infective hexacanth shows bilateral symmetry in cellular organization. The mature hexacanth is armed with three pairs of oncospheral hooks of a heterogeneous electron density. It is covered by a thin layer of the oncospheral tegument, possessing characteristic bubble-like processes at the surface. Within the infective hexacanth larva five cell types were distinguished: (1) a binucleated subtegumental cell; (2) the U-shaped, tetranucleated penetration gland; (3) two nerve cells; (4) three types of somatic cells represented by: i) myocytons of both somatic and hook musculature, ii) numerous degenerating micromeres with pycnotic nuclei and iii) a new oncospheral cell type, the interstitial cell, that has never been observed in any other hexacanth; and (5) large germinative cells with characteristic prominent nucleoli in their large spherical nuclei. Functions of all the cell types are described on the basis of the obtained ultrastructural characteristics and previously published reports. The mode of the penetration gland secretion is classified as apocrine. Flame cells have never been observed within the hexacanth of E. salvelini. The results of the present study, comparing the functional aspects of the ultrastructure of the hexacanths of E. salvelini with literature data on the oncospheres of other bothriocephallideans and diphyllobothriideans, suggest potential phylogenetic and evolutionary criteria for determining relationships among these groups of tapeworms., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The present paper describes two distinct morphological features of ovine interdigital sinus, which were examined by means of scanning electron microscopy. In the sweat glandular component, acini with epithelial cells exhibiting a paved appearance and apocrine secretion were observed. In the same gland, other acini with cells exhibiting different luminal surfaces and simultaneous apocrine and merocrine secretion were recorded. The numerous hairs embedded within the waxy material of the sinus exhibited two types. The first type, with a round profile, had a special leaflet structure on the tip, whereas the second type had a convex profile. The comparative differences and probable functional relations of these integumentary structures are discussed. The mixed picture of the epithelial cells of the sweat glands suggests the release of different products. The hair microstructure correlated with the mechanism of hold and release of the secretory material of the interdigital sinus.

This article describes the scanning electron microscopic (SEM) features of the ovine interdigital sinus. The lumen was filled with a dense secretory material and quite a number of hairs embedded in the luminal content. For SEM purposes, the sinus was divided into three parts: base, body and neck. At the cut surface, the wall exhibited significant folds which were almost absent in the base, the very short blind end of the sinus. The wall had three layers: epidermis, dermis and fibrous capsule. Stratified epithelium with a prominent keratin layer faced the lumen. The inner surface was similar to the skin surface; however, it was coarser due to folds. The fibrous capsule was composed mainly of dense connective tissue, constituting the outermost layer of the wall. The dermis contained common skin structures including sebaceous glands, hair follicles, arrector pili muscles and apocrine glands. Sebaceous glands appeared as groups of bubbles if they were not collapsed. Apocrine glands generally appeared as a group of coiled tubules. They frequently exhibited apocrine blebs, which is a feature of apocrine secretion. SEM was able to locate some secretory vesicles in the lumen of apocrine tubules which is frequently filled by secretory content. Thus, the apocrine tubules exhibited classical features of apocrine secretion.

The present study revealed in detail the subcellular localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotal skin, a specific body region. The apocrine glandular cells were equipped with a varying number of secretory granules, a well-developed Golgi apparatus and abundant cisternae of the rough endoplasmic reticulum within their cytoplasm. In these cells, reactive gold particles representing lysozyme were detectable in the secretory granules as well as the Golgi apparatus and elements of the rough endoplasmic reticulum. Additionally, the antimicrobial peptide group of beta-defensin was also localized in the above-mentioned ultrastructures of the secretory cells. The presence and secretion of such substances that may serve as a non-specific defense against microorganisms are suggestive of the protective effect of the secretory production elaborated by the apocrine glands.

The morphology of the intermandibular gland of the Lesser mouse deer (Tragulus javanicus), which plays an important function in marking area and territory and in the reproductive behaviour of the animal, was examined using immunohistochemistry, lectin histochemistry and scanning electron microscopy. The gland was composed of sebaceous and apocrine glandular material. Sebaceous glands occupied a greater area of the total gland and consisted of many large lobules with polyhedral cells having a pale cytoplasm. The sebaceous gland, being holocrine, possessed no special secretory ducts. The apocrine gland was lined by cuboid cells and the secretory products were often seen in the apical portions of the cells. Myoepithelial cells contained actin filaments lining the basal membranes of the apocrine gland and were surrounded by nerve fibres which immunostained with protein gene product 9.5. The secretion of the gland appears to be a mixture of larger amounts of lipid material from sebaceous glands, and glycoconjugates secreted by both sebaceous and apocrine glands. Lectin histochemistry detected these as galactose, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, D-mannose and D-glucose. The male gland was larger in size and contained more N-acetyl galactosamine and N-acetyl glucosamine in its secretion than the gland of the female. This implied the presence of sexual differences in secretions in the intermandibular gland of the Lesser mouse deer.

The ceruminous glands in the skin of the human external auditory canal are modified apocrine glands, which, together with sebaceous glands, produce the cerumen, the ear wax. Cerumen plays an important role in the protection of the ear canal against physical damage and microbial invasion. We studied the morphology of the glandular cells by light and electronmicroscopy. Antimicrobial and cytoskeletal components of the ceruminous glands were investigated by immunohistochemical methods. Numerous antimicrobial proteins and peptides are present in the ceruminous glandular cells: beta-defensin-1, beta-defensin-2, cathelicidin, lysozyme, lactoferrin, MUC1, secretory component of IgA. These data indicate a crucial role in the innate host defense against diverse pathogens. The apocrine secretion mechanism is a special mode of secretion by which the apical part of the cell cytoplasm surrounded by a membrane is pinched off. We could show that the presence of actin filaments, CK 19 and CK 7, seems to play a role in the pinching-off mechanism. Finally, we showed the secretion of lipid vesicles from the ceruminous gland. We could extend the number of detected antimicrobial peptides and proteins in human ceruminous glandular cells that protect the surface of the external auditory meatus. In addition, we detected proteins involved in the apocrine secretion mode of the ceruminous gland.

Cytochemistry of glycoconjugates in the apocrine glands in the scrotal skin of the horse was studied using cytochemical methods for electron microscopy, particularly lectin cytochemistry. The secretory cells possessed a variable number of secretory vesicles, a well-developed Golgi apparatus, and abundant cisternae of the rough endoplasmic reticulum. Additionally, the basolateral plasma membrane formed numerous interdigitating folds. Glycoconjugates with vicinal diol groupings were present predominantly in the secretory vesicles, the Golgi apparatus, the surface coat of the plasma membrane, and the majority of the intracellular membranes. With lectin cytochemistry, the secretory vesicles of the glandular cells exhibited glycoproteins with different terminal sugars (alpha-D-mannose, beta-D-galactose beta-N-acetyl-D-glucosamine, and sialic acid). Several sugars were distinctly prominent in the surface coat of the plasma membrane of the secretory cells. The cytochemical properties of the complex glycoconjugates found are discussed in relation to the specific functions of the glandular secretions. These glands may have an important role in not only thermoregulation but protection of the scrotal skin, a specific body region.

In this study, we conducted a light microscopic and ultrastructural analysis of the integument of the one-humped camel (Camelus dromedarius). In general, the epidermal strata of the camel integument appeared typical of those found in non-desert mammals. Two cell populations were noted in the stratum basale: one with a flat, non-serrated base and the other with a highly serrated base. Typical fine structure was observed in keratinocytes of the stratum spinosum and stratum granulosum. The stratum corneum was six to 10 cells thick. Within the different strata, overall cell morphologies and the general distribution and relative abundance of cellular organelles appeared typical. Dermal features included the presence of myoepithelial cells surrounding apocrine tubular glands. Inter- or intracellular canaliculi within the secretory cells of the apocrine glands, reported to be present in certain other non-desert mammals, were not evident in the camel. Together, these data indicate that while the camel is clearly adapted for a desert lifestyle, these adaptations do not include significant specializations at the cellular or subcellular level in the integument.

Originally defined as a lymphokine inhibiting the random migration of macrophages, the macrophage migration inhibitory factor (MIF) is an important mediator of the host response to infection. Beyond its function as a classical cytokine, MIF is currently portrayed as a multifunctional protein with growth-regulating properties present in organ systems beyond immune cells. In previous studies, we detected substantial amounts of MIF in the rat epididymis and epididymal spermatozoa, where it appears to play a role during post-testicular sperm maturation and the acquisition of fertilization ability. To explore its presence in other species not yet examined in this respect, we extended the range of studies to the bull. Using a polyclonal antibody raised against MIF purified from bovine eye lenses, we detected MIF in the epithelium of the adult bovine epididymis with the basal cells representing a prominently stained cell type. A distinct accumulation of MIF at the apical cell pole of the epithelial cells and in membranous vesicles localized in the lumen of the epididymal duct was obvious. In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas MIF accumulation was evident at the apical cell surface and in apical protrusions. By immunoelectron microscopy of the adult bovine epididymis, we localized MIF in apical protrusions of the epithelial cells and in luminal membrane-bound vesicles that were found in close proximity to sperm cells. Although the precise origin of the MIF-containing vesicles remains to be delineated, our morphological observations support the hypothesis that they become detached from the apical surface of the epididymal epithelial cells. Additionally, an association of MIF with the outer dense fibers of luminal spermatozoa was demonstrated. Data obtained in this study suggest MIF release by an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized in the basal cells of the epithelium and in the connective tissue could be responsible for regulating the migration of macrophages in order to avoid contact of immune cells with spermatozoa that carry a wide range of potent antigens., (Copyright (c) 2006 S. Karger AG, Basel.)

Myoepithelial cells present in exocrine glands cause secretion from the glands by contraction. They have mixed characteristics with regard to cytoskeletal elements, containing both epithelial-type intermediate filaments and smooth muscle-type myofilaments. For further characterization, myoepithelial cells from bovine apocrine sweat glands and tracheal glands were here examined with special attention to the cell-substratum adhesion system. Immunofluorescence microscopy using a panel of antibodies against adherens-type junctional and hemidesmosomal proteins demonstrated two types of cell-substratum junctions in myoepithelial cells from both glands. Type-I hemidesmosomes (HDs) consisting of plectin, BP230, integrin alpha6beta4, and BP180 were thus observed as punctate arrays longitudinally arranged along myoepithelial cell surfaces, while adherens-type junctions were similarly evident as linear rib-like structures. Double-label immunofluoresence revealed the two junctions to be distributed in a mutually exclusive or independent manner. Electron microscopy further demonstrated that apocrine myoepithelial cells surround secretory epithelial cells completely, without any gaps, HDs being abundant along the basement membrane, but with no distinct structures in the inter-hemidesmosomal regions. Immunoelectron microscopy, however, revealed an interhemidesmosomal localization of vinculin, pointing to the existence of adherens-type junctions. Secretory epithelial cells in tracheal glands were found not to be completely covered with myoepithelial cells, so that more than half of them are directly attached to the basement membrane, where they form type II-HDs lacking BP230 and BP180, but no detectable adherens junctions, like epidermal basal cells and sebaceous gland cells. These observations demonstrate that, in addition to their cytoskeleton, myoepithelial cells have both epithelial- and smooth muscle-type cell-substratum adhesion structures, i.e. HDs and dense plaque-like adherens junctions.

The localization and chemical nature of complex carbohydrates in the ceruminous glands of the Japanese miniature (Shiba) goat were studied using light and electron microscopic histochemical methods, particularly lectin histochemistry. The epithelial cells and luminal secretion of the caprine ceruminous glands contained large amounts of neutral and smaller amounts of acidic glycoconjugates with different terminal sugars (alpha- d-mannose, alpha-L-fucose, alpha-N-acetyl-D-galactosamine, beta-D-galactose, beta-N-acetyl-D-glucosamine, and N-acetyl-neuraminic acid). Several sugars (alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine, and N-acetyl-neuraminic acid) were also detectable in the secretion of the sebaceous glands. The results obtained are discussed with regard to the specific function of the glandular secretion mixture. The complex glycoconjugates found in the ceruminous gland secretion may control viscoelasticity of and bacterial proliferation within the cerumen in order to protect the external auditory canal against physical damage or microbial attacks.

Apocrine glands of Moll are regular components of primate eyelids. We studied the distribution and localization of these glands in three different primate species, the common marmoset, the rhesus monkey, and the hamadryas baboon. In addition, we tested the primate glands of Moll with antibodies against antimicrobial proteins, cytoskeletal proteins and the androgen receptor. The glands of Moll differ in abundance and distribution in different monkeys. In the common marmoset, a representative of the New World monkeys, Platyrrhini, the apocrine glands are frequently found at the lid margin and in the overlying epidermis of the lid. In the rhesus monkey and the hamadryas baboon, representatives of Old World monkeys, Catarrhini, apocrine glands are rarer and located predominantly at the margin of the lid. The immunohistochemical analysis indicates the presence of a variety of antimicrobial proteins, e.g. lysozyme, beta-defensin-2, adrenomedullin, lactoferrin, and IgA, in these glands. Interestingly, there are basically no androgen receptors in the nuclei of apocrine glands at the lid margin in all three monkey species. In the common marmoset, however, androgen receptors are found in apocrine glands of the overlying epidermis of the lid. We speculate that the glands of Moll are derived from apocrine glands as found in the skin of the entire body in New World monkeys which developed at the lid margins of higher primates and humans into specialized glands secreting agents of host defense in the eye., (Copyright 2004 S. Karger AG, Basel)

The function of the human gland of Moll of the eyelid is not exactly known. We studied the secretory and cytoskeletal components of these apocrine glands in males and females by immunohistochemical methods, and the ultrastructural organization of the glandular cells with an electron microscope. The glands of Moll are exclusively located at the margin of the eyelids and their ducts empty into the lash follicle. Immunohistochemical staining for actin and cytokeratins CK19 and CK7 points to the involvement of actin in the pinching-off mechanism of the apical cell protrusion during apocrine secretion and to a stabilizing role for the cytokeratins in this apical region of the glandular cells. The presence of the bacteriolytic enzyme lysozyme, the membrane-associated mucin 1, and the immunoglobulin A and its secretory component within the gland suggest a function in local immune defense. The presence of a variety of sugar components in the secretory product was verified by lectin histochemistry and periodic acid Schiff and Alcian blue stain. We suppose that these apocrine glands are active from birth in producing agents against pathogenic microorganisms in the eyelid shaft and on the ocular surface.

The distribution and selectivities of glycoconjugates in the ceruminous glands of the North American raccoon (Procyon lotor) were studied by light and electron microscopic histochemical methods, particularly lectin histochemistry. In the modified apocrine glands present, the apocrine secretion mode was combined with exocytosis, whereby the secretory epithelium and the luminal secretion of the ceruminous glands exhibited considerable amounts of complex carbohydrates with various terminal sugars (alpha-D-mannose, beta-D-galactose, alpha-L-fucose, alpha-N-acetyl-galactosamine, beta-N-acetyl-D-glucosamine, N-acetyl-neuraminic acid). Alpha-L-fucose and N-acetyl-neuraminic acid were distinctly prominent in secretory granules or within the free surface coat of the plasma membrane of the glandular cells, as well as in the luminal secretion. Several free sugars (alpha-D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine) were also detectable in the secretion of associated sebaceous glands. The ceruminous gland secretion may control viscoelasticity and/or bacterial degradation of the glandular secretion mixture to improve the protection of the external auditory canal against physical damage or microbial contamination.

Cell secretion is an important physiological process that ensures smooth metabolic activities, tissue repair and growth and immunological functions in the body. It occurs when the intracellular secretory materials are released to the exterior; these may be in the form of lipids, protein or mucous and may travel through a duct system or via blood to reach the target organ. To date three types of secretory mechanisms have been characterized, they include apocrine, holocrine and exocytosis. Apocrine secretion occurs when the release of secretory materials is accompanied with loss of part of cytoplasm. The secretory materials may be contained in the secretory vesicles or dissolved in the cytoplasm that is lost during secretion. In holocrine secretion, the entire cell is secreted into the glandular lumen, and it is presumed that the intended secretory materials are contained in the cell cytoplasm. Exocytosis is the most commonly occurring type of secretion; here the secretory materials are contained in the secretory vesicles and released without loss of cytoplasm. Apocrine secretory mechanisms have not been properly discussed; for example the biochemical and physiological pathways that regulate apocrine secretory process are not clearly known. Similarly, the plasma membrane dynamics during apocrine secretion has not been researched. In other glands morphological features during apocrine secretion have not been documented. The current paper reviews what is known about apocrine secretion, recent findings and highlights on the unresolved areas for future research.

The ultrastructural morphology of a ceruminous gland adenoma in the middle ear was examined electron microscopically. The epithelial tumor cells displayed apocrine caps, microvilli, cell junctions, secretory granules, vacuoles, lipid droplets and siderosomes, which are the characteristic ultrastructural features of apocrine glands. Concentric membranous bodies of the endoplasmic reticulum, phagocytic activity of the tumor cells, intracytoplasmic lumina, ciliated cells and also spiny collagen in the tumor stroma could be seen. The myoepithelial cells are an important tumor marker in the differential diagnosis between ceruminomas and adenomas of the middle ear. The ectopic origin in the modified apocrine ceruminous glands, the specific localization, the clinical features and the extremely rare occurrence of the ceruminoma makes this tumor a unique neoplastic entity., (Copyright 2002 S. Karger AG, Basel)

Background: Desmoplastic trichoepithelioma is a benign neoplasm considered to have follicular differentiation. Its sweat gland- or sebaceous-lines of differentiation have been also reported. There have been, however, only a few reports regarding extensive immunohistochemical and ultrastructural investigations of this neoplasm., Methods: Histopathological and immunohistochemical studies were performed on three cases of desmoplastic trichoepithelioma, comparing it with normal skin. One of these cases was ultrastructurally investigated., Results: The cord-like basaloid nests were reacted with the anti-cytokeratin (CK)1/5/10/14, -CK5/8, -CK14 and -CK15 antibodies, but not with the anti-CK6 antibody. Similar findings were observed in the outer layers of the normal follicular outer root sheath. Basaloid cell nests in one case, which showed ductal structures in the nests, also expressed CK7, CK8/18 and CK19. These keratins were also detected in the normal sweat glands. In addition, CK8/18 and CK19 were expressed in the basal cells of the outer root sheath. Keratinous cysts had inner reactions with the anti-CK10/11 and -CK6 antibodies, and outer reactions with anti-CK5/8 and -CK14 antibodies. Ultrastructurally, the cells in the cord-like nests were basically immature and basaloid in appearance. A few cells contained Odland bodies, which were also observed in the normal apocrine acrosyringeum. The ductal structure was lined by the cells which bore numerous microvilli in the luminal surface., Conclusion: The cells in desmoplastic trichoepithelioma are suggested to be in close association with the basal cells in the outer root sheath, which can differentiate into various parts of the folliculosebaceous apocrine unit.

The ultracytochemical localization of adenylate cyclase (AC) was studied after stimulation with pituitary adenylate cyclase activating peptide (PACAP) in human sweat glands. PACAP stimulated AC in both eccrine and apocrine glands. In the secretory cells, enzymatic activity was associated with membranes involved in the secretory mechanism. In both glands, the cells of the excretory duct and myoepithelial cells presented AC activity. These localizations of enzymatic activity suggest a role for PACAP in regulating glandular secretion.

An apocrine adenocarcinoma was observed in the subcutis of the abdomen of golden hamster. Histologically, the tumor cells irregularly formed multiple layers of cysts and some detached cells were presented in the cystic space. PAS stain with alpha-amylase digestion revealed PAS-positive alpha-amylase-resistant granules in the cytoplasm. Immunohistochemically, cytokeratin was demonstrated in the tumor cells. By electron microscopy, the tumor cells had an oval nucleus with invagination, abundant cytoplasmic organelles and microvilli protruding into the intercellular spaces.

The products of the human apocrine axillary glands contain volatile steroids which act as pheromones. The steroidal structure of these pheromones implies that the axillary glands should be able to synthesize cholesterol which is the essential precursor of these molecules. Since important steps in cholesterol synthesis are localized within peroxisomes, we investigated the occurrence and the putative role of peroxisomes in the axillary glands at protein and mRNA levels by immunocytochemistry, Western blotting, and RT-PCR. Numerous peroxisomes were localized in the cells of the apocrine glands by immunocytochemistry, and the presence of catalase was confirmed by Western blotting and RT-PCR. Additionally, RT-PCR revealed the presence of mRNAs of two peroxisome-associated enzymes of the cholesterol biosynthetic pathway, mevalonate kinase and farnesyl diphosphate synthase. The results suggest that the peroxisomes in the human apocrine axillary glands may play a pivotal role in the biosynthesis of pheromones.

Prostate-specific antigen (PSA), a serine protease thought to be exclusively produced by the prostate epithelial cells, has been recently found in human breast tissues and fluids. PSA in breast cancer is associated with the presence of steroid-hormones and receptors, and its presence seems to be a favourable prognostic indicator. In order to clarify whether the cells lining breast cysts may represent the source of PSA found in human breast cyst fluid, we performed an ultrastructural immunolocalization of PSA in the cells surrounding Type I breast cysts, obtained from breast cyst fluids of women affected by breast gross cystic disease, the most commonly occurring benign breast lesions associated with increased cancer risk. These apocrine cells show morphological features typical of actively synthesizing and secreting cells, and a PSA labelling distributed on free ribosomes, RER cisternae, and secretory granules, indicating that the metabolically active apocrine cells lining the Type I cysts are responsible for the production and secretion of PSA in Type I breast cyst fluids. The synthesis and intracystic accumulation of this serine protease in biosynthetically active apocrine Type I cysts can play an important role in the natural history of breast gross cystic disease as well as in the mechanism of cyst evolution.

A 13-year-old male Shetland Sheepdog with progressive exophthalmos had a neoplastic mass in the ocular adnexa. Histologically, this neoplasm was composed of duct-forming epithelial cells with decapitation secretion. Tumor cells invaded the globe through the tunica conjunctiva and replaced the vitreous body. The cornea, iris, ciliary body, and retina were extensively destroyed. Both the epithelial and spindle-shaped myoepithelial cells showed nuclear atypia and mitotic activity in the globe. The primary tumor was diagnosed as adenocarcinoma, probably originating from apocrine sweat glands of the eyelid, and the infiltrating intraocular neoplasm was diagnosed as a malignant mixed tumor.

Harderian glands of male albino rats were stimulated with secretagogues and examined by transmission and scanning electron microscopy for the purpose of studying the apocrine secretory mechanism. Rats in the control group were perfused with standard HEPES-buffered Ringer's solution. Their glandular endpieces showed wide lumina that contained few secretory materials; spontaneous exocytosis was sometimes observed. However, there were no features suggestive of an apocrine secretory mechanism or myoepithelial cell contractions. After stimulation with NaF+AlCl3 or carbachol in HEPES-buffered Ringer's solution, the rats shed "bloody tears" and the glandular lumina were jammed with apical protrusions, cytoplasmic material and secretory products. The basal surface of the glandular cells showed bulging caused by myoepithelial cell contraction. Perfusion with HEPES-buffered Ringer's solution containing papaverine inhibited secretagogue-induced myoepithelial cell contraction but not the enhanced secretory activities of the glandular cells. The present results demonstrate that the Harderian gland of the rat can release secretory material not only by exocytosis, but also by an apocrine mechanism under stimulating conditions, and that myoepithelial cell contraction may not be involved in causing apical protrusion in the glandular cells.

Alkaline phosphatase (ALP) is a membrane-bound enzyme that catalyzes the hydrolysis of inorganic and organic monophosphate esters at alkaline pH. Although the functions of ALP are poorly understood, it is believed to be involved in membrane transport. Because little is known about the functions and distribution of ALP in the sweat glands, we studied the localization of ALP in human sweat glands with light and electron microscopic enzyme cytochemistry. In eccrine sweat glands, ALP was restricted to the cell membranes of intercellular canaliculi. Luminal cell membranes of secretory cells that are in continuity with intercellular canaliculi did not show ALP activity. These results suggest that ALP participates in the production of primary sweat at intercellular canaliculi. In apocrine sweat glands, basal cell membranes of secretory cells and myoepithelial cell membranes that were in apposition with each other showed ALP activity, where as no activity was seen in eccrine sweat glands. These differences in the distribution of ALP in myoepithelial cells between eccrine and apocrine sweat glands might be related to the functional differences of these sweat glands. ALP histochemistry could help to diagnose and to determine the direction of differentiation in sweat gland tumors.

The distribution of the lysosomal enzymes cathepsin B, lysozyme, chymotrypsin, and neutrophil elastase was examined in eccrine, apocrine, and sebaceous glands using a postembedding immunogold labeling procedure. Various amounts of cathepsin B were detected in all glands. Lysozyme, however, was detected in apocrine glands only. The other two lysosomal enzymes were not detectable immunologically. In apocrine and eccrine glands, anti-cathepsin B antibody labeled all secretory granules. In sebaceous glands, only the peripheral layer of cells showed immunological activity for cathepsin B. In apocrine glands, granules containing remnants of cristae were more intensively labeled than those lacking cristae which supports the assumption that both granules are derived from mitochondria by acquiring lysosomal enzymes. The enzymes convert mitochondria to granules with cristae and finally to granules without cristae. Thus the difference in morphology is part of a spectrum of the degradation of mitochondria to granules.

The apocrine nevus (AN) is a rare tumor occurring in the upper chest and the axilla. We report a case of a AN in a 33-year-old female occurring unilaterally. The presenting complaint related to tenderness and swelling in the right axilla. The initial impression was hidradenitis suppurativa. The gross specimen revealed the presence of irregular thickening just beneath the dermal subcutaneous interface. Microscopically the lesion was composed of mature apocrine glands with apical snouts. The glands were arranged in lobules divided by thin fibrous septa. Immunohistochemical studies revealed the following profile in the glandular epithelium: positive low molecular weight cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein reactivity and negative high molecular cytokeratin and S-100 protein reactivity. Carcinoembryonic antigen reactivity was found in the duct epithelium. Ultrastructural studies revealed cells lining the lumen of the glands with a concentration of granules in the apical region and light and dark granules. These findings support the previously described light microscopic observations and provide unreported ultrastructural studies in this rare tumor.

The infraorbital gland of the Japanese serow was examined under the scanning electron microscope to clarify the nature of apocrine secretion. The size and number of apocrine blebs on secretory cells varied markedly from cell to cell; as the size of blebs increased, their numbers decreased. After pinching off of blebs, crown-shaped structures were retained on the remaining apical surface of secretory cells. Detached free blebs in the lumen were spherical in shape with smooth surfaces. Secretory cells having blebs of similar size formed small clusters in tubules, and these clusters consisted of cells without blebs, cells with small blebs, cells with medium-sized blebs and cells with large blebs. The present evidence obtained by scanning electron microscopy is very much in harmony with results obtained at the light-microscopic level in terms of the sizes and numbers of blebs during apocrine secretion. Moreover, our evidence suggests the capacity for production of variously sized blebs in secretory cells and the presence of segmentary differences, in terms of apocrine activity, in tubules.

The histopathological and cytological findings of a caruncular oxyphilic adenoma (oncocytoma) in a 85 year-old male is described. The columnar or polygonal tumor cells contained numerous eosinophilic fine granules (mitochondria). They showed papillary proliferation and cyst formation. Electron microscopically, some tumor cells contained amorphous cytoplasm and small numbers of mitochondria in their apical snout, and secreted the contents in the extracellular spaces. It seemed that the tumor cells originated from the ductal epithelia in the caruncle and microscopically some cells simulated apocrine type secretion.

We studied the localization of the epidermal growth factor (EGF) in eccrine and apocrine sweat glands with light microscopic and electron microscopic immunohistochemistry. Anti-human EGF (anti-hEGF) polyclonal antiserum and anti-hEGF monoclonal antibody (MAb) were used for the study. Light microscopic immunohistochemistry with monoclonal and polyclonal antibodies showed that hEGF-like immunoreactivity was strongly positive in the myoepithelial cells and weakly positive in the secretory cells of eccrine sweat glands. In apocrine sweat glands, it was strongly positive in the secretory cells as well as in the myoepithelial cells. Immunoelectron microscopy with polyclonal antibody showed that hEGF-like immunoreactivity was present in secretory granules of apocrine secretory cells. These granules had mitochondrion-like internal structure. No reactivity was observed on the eccrine secretory cells by immunoelectron microscopy. Neither dark cell granules nor mitochondria in eccrine secretory cells were labeled with anti-hEGF antibody. In both eccrine and apocrine sweat glands, hEGF-like immunoreactivity was diffusely present in the cytoplasm of myoepithelial cells. However, nuclei and mitochondria of myoepithelial cells were devoid of immunoreactivity for hEGF. Our observations indicate that apocrine sweat glands may secrete more hEGF in the sweat than eccrine sweat glands.

A case of Lafora's disease diagnosed by skin biopsy is reported. Lafora's bodies, the hallmark of myoclonal epilepsy, were present in the epithelial cells of the apocrine glands. Therefore, the skin biopsy of the axilla proved to be very useful in the diagnosis of this entity. A striking feature of the case was that Lafora's bodies were only found in apocrine glands, whereas the eccrine glands were free of them.

The distribution of carbohydrate residues in eccrine and apocrine glands of normal human skin was studied using a post-embedding technique with Lowicryl K4M. Thin sections were incubated with Ulex europaeus agglutinin I (UEA I), wheat germ agglutinin (WGA), peanut agglutinin (PNA), concanavalin A (Con A), soybean agglutinin (SBA), and dolichos biflorus agglutinin (DBA). All lectins except for PNA showed labeling of the plasma membranes of dark cells, clear cells, and apocrine cells. The granules of the eccrine gland were labeled with all lectins except for DBA. The mitochondrial granules of the apocrine gland were not labeled with any lectin, whereas the lysosomal granules showed a positive reaction with all lectins except for PNA. After incubation with PNA, in eccrine glands the granules were the only structure labeled, whereas in apocrine glands the luminal side of the plasma membrane and cytoplasmic vesicles beneath it were the only structures labeled.

The secretory process in swine apocrine sweat glands were studied by electron microscope. The sweat appeared to result from three different mechanisms: (a) fluid transport, probably involving a region of complex cellular interdigitations adjacent to the basement membrane, (b) exocytosis of vesicles, which in this species seem to be derived from the Golgi apparatus and finally (c) apocrine secretion.

5 alpha-Dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay in the crude nuclear and cytoplasmic fractions of the axillary skin of both male and female patients with osmidrosis and the levels compared with those of nongenital skin. The intranuclear levels of DHT were 1.44 +/- 0.22 and 1.77 +/- 0.38 pg/micrograms DNA in men and women, respectively. Those of testosterone were about 10% of DHT levels. In the skin of nontarget regions nuclear DHT was much scarcer or undetectable. Cytosolic androgen receptors in isolated apocrine glands were also measured using 3H-R1881 as a ligand. Typical androgen receptors were present in all of eight patients (KD = 1.32 +/- 0.24 X 10(-9)M, Bmax = 10.3 +/- 0.51 fmol/mg protein). Neither the intranuclear androgen concentrations nor the cytosolic androgen receptor levels were significantly different between the two sexes. These data indicate clearly that the apocrine gland of patients with osmidrosis is a typical androgen target organ, irrespective of sex, and suggest that nuclear DHT in the axillary skin of women is derived from not only testosterone but also other precursors, especially in consideration of the very low serum concentrations of testosterone in females.

Two secretory mechanisms (eccrine and apocrine) were observed by transmission and scanning electron microscopy in the same secretory cells of the human ceruminous glands. The eccrine secretion occurs as a typical exocytosis by fusion of the limiting membrane of the secretory granule with the apical plasmalemma. The apocrine secretion is more complex and takes place by sequential steps: bulging of the cellular apex into the lumen, constriction of the projection, and detachment of it from the cell. This mechanism generally causes the removal of the entire projection all at once by decapitation at its base; some variations of this process have been found, however, and are described in the present work. A double membrane, apparently separating the apical protrusion from the rest of the cell, is noticeable in our photographs. Nevertheless, even if this membrane is very similar to a demarcation layer, we consider it as an intercellular double membrane separating two obliquely sectioned cells.

The secretory portion of the apocrine sweat gland of the human external auditory meatus which is also called the ceruminous gland was observed by transmission and scanning electron microscopy. The secretory glandular cells contain a well developed smooth endoplasmic reticulum and Golgi apparatus. Cisternae of rough endoplasmic reticulum are often closely applied to large round mitochondria. These large mitochondria have no relationship to the secretory granules. Near the concave surface of the Golgi lamellae several tubules can be found. In these golgi-associated tubules a dark substance may accumulate to form specific large dense granules. Many less dense droplets or vacuoles may appear in these dark prosecretory granules and become liberated from their surface. Vacuoles formed in this manner then migrate to the apical cell surface and often discharge their contents into the gland lumen by the mechanism of exocytosis. Also, some of these vacuoles may be released into the lumen by the pinching off of small protrusions of cytoplasm, that is, they are released by the so-called apocrine secretory mechanism. Acid phosphatase activity was demonstrated not only in the dark prosecretory granules but also in clear vacuoles situated at the apical end of the cell and in the gland lumen. Such a histochemical finding may indicate that the secretory substance of the apocrine sweat gland may contain hydrolytic enzymes derived from lysosomes, which are the prosecretory granules of this gland, and these enzymes may play a role in dissolution and break down of the material extruded into the lumen by apocrine secretion. Apocrine secretory process of various sizes were observed on the luminal surface with the scanning electron microscope.

Electron microscopic examination of apocrine glands revealed three types of secretion: merocrine apocrine, and possible holocrine. In the merocrine type of secretion numerous vesicles originating in the Golgi area discharged their granular contents into the lumen of the gland. In the apocrine type of secretion three stages were observed: (1) formation of an apical cap; (2) formation of a dividing membrane at the base of the apical cap; and (3) formation of tubules avove the dividing membrand that extended parallel to the membrane and led to a separation of the apical cap from the underlying cell, In the holocrine type of secretion individual secretory cells or even strands of secretory cells were dischard into the lumen of the gland.

The acrosyringium of human apocrine sweat apparatus has been studied by light and electron microscopy using horizontal continuous serial sections. The apocrine acrosyringium is composed of 3 structurally different portions, a highly keratinizing upper portion, an incompletely keratinizing midportion, and a least keratinizing lower portion. Throughout these 3 portions, there are 2 distinctly different but closely inter-related cellular units, namely (I) a keratinization process lacking membrane-coating granules but containing keratohyalin droplets occurring in its inner cell layer, and (II) a keratinization process rich in membrane-coating granules and containing keratohyalin granules occurring in its outer surrounding concentric cell layers. In contrast to the inner cell layer, the outer cell layer does not belong to the duct proper but rather should be considered as the periacrosyringeal complex layer which is specially differentiated to envelop the intra-epithelial duct. This apocrine acrosyringeal complex in the hair follicle seems to be essentially similar to that of the eccrine apparatus in the epidermis.

An operatively removed apocrine carcinoma of the breast from a 62-year-old Japanese lady has been observed by the ABC method, using the monoclonal antibody 115D8. The cancer cells and metaplastic epithelia exhibited similar ultrastructural findings (an apical snout, apocrine granules, etc.) as the apocrine sweat gland cells, although no evidence of apocrine secretion could be detected. The immunohistochemical testing, using monoclonal antibody, 115D8, showed an apical, linear, dot-like, staining in the supranuclear regions on the apocrine sweat gland cells and on the apocrine metaplastic cells of the mammary gland. Similar stainability also was observed in the well-differentiated area of the apocrine carcinoma, while a heterogeneity in staining, such as unstained cells and diffuse cytoplasmic-stained cells were found in the poorly-differentiated areas. These abnormal staining patterns indicate the malignant changes of the apocrine cells.

Lipid synthesis by freshly isolated human apocrine glands has been measured by the incorporation of [U-14C] acetate. Incorporation is linear over 6 h at 1010 +/- 282 pmol/mg wet weight/h (n = 11; mean +/- sem). The lipid classes, as percentages of the total lipid synthesized, were found by TLC to be cholesterol 12.3 +/- 2.0, mono-glycerides 7.5 +/- 1.5, 1,2 di-glycerides 3.0 +/- 0.9, 1,3 di-glycerides 3.5 +/- 0.5, tri-glycerides 28.4 +/- 1.8, free fatty acids 2.0 +/- 0.4, lysolecithin 15.4 +/- 3.9, sphingomyelin 9.9 +/- 4.3, phosphatidyl-choline 8.4 +/- 0.4, phosphatidyl-ethanolamine -inositol and -serine 1.8 +/- 0.1, phosphatidic acid and cardiolipin 3.3 +/- 0.5, and unidentified 3.3 +/- 0.5 (mean +/- sem, n = 5). Glands were maintained on permeable supports. After 10 d maintenance, electron microscopy showed that the cellular architecture had been preserved, that the ATP contents were the same as in freshly isolated glands, and that [U-14C] acetate incorporation was not significantly altered at 851 +/- 237 pmol/mg/h (n = 18). The addition of 3 microM testosterone had no effect on acetate incorporation at 844 +/- 231 pmol/mg/h (n = 18). The lipid classes and their proportions were similar to the values for fresh glands after 10 d maintenance both with and without testosterone.

The sweat ducts of human eccrine and apocrine (ceruminous) glands were observed with the transmission electron microscope. Both the dermal and epidermal segment of the eccrine as well as apocrine ducts consist of two epithelial layers: luminal cells and peripheral cells. Well-developed microvilli, occurrence of cored vesicles, dense granules, multivesicular bodies and phagosomes in the adluminal filamentous zone, and a strong accumulation of mitochondria in the basal part of the duct epithelium at the dermal segment, as well as an accumulation of small clear vesicles beneath the surface of the luminal cells of the epidermal segment are all prominent in the eccrine duct and concomitant with the special function of the human eccrine duct, i.e., absorption of ions to make the sweat hyotonic and an active endocytosis of some material from the sweat. All of the above enumerated characteristics of the eccrine duct are only rarely or never seen in the apocrine duct. On the other hand, lipid droplets appear in the peripheral cells in a certain level of the apocrine duct near its orifice into the hair follicle, suggesting a kind of metaplasia towards the sebaceous gland. Epidermal duct cells of both eccrine and apocrine sweat glands may keratinize. In the eccrine duct the process in the duct cells precedes the surrounding keratinocytes, while in the apocrine duct the relationship is reversed.