The cytology of apocrine sweat glands

Summary The apocrine sweat glands of cat and monkey have been studied by light and electron microscopy. The apocrine secretory cells of the cat are columnar cells with prominent apical cytoplasmic caps extending into the gland lumen beyond the zone of terminal bars (zonulae occludentes). Many secretory vacuoles are present in the cytoplasm, and they contain acid mucopolysaccharide demonstrable by light microscopy. These secretory vacuoles arise from prosecretory vacuoles in the region of the Golgi apparatus and are liberated from the apical cell surface as in other merocrine cells. The apocrine duct is short and the cells have scant mitochondria. The apocrine secretory cells of the monkey have secretory vacuoles similar to those of the cat but are fewer in number. The monkey apocrine cells also contain unidentified bodies similar to those seen in Langerhans cells of the epidermis. These cells liberate secretory vacuoles in a merocrine manner. Apocrine or decapitation secretion is regarded as an artifact.This investigation was supported in part by United States Public Health Service research grants GM-03784 and GM-10102 from the Institute of General Medical Sciences.     

Localization of steroid hormone receptors in the apocrine sweat glands of the human axilla

The apocrine axillary glands, regarded as pheromone-producing scent glands, do not begin to function until puberty. Accordingly, sex hormones should have an impact on their activity, and the present study was designed to investigate the localization of androgen receptor (AR) and estrogen receptors (ER and ER) in those glands. Strong nuclear immunoreactivity for AR and ER was found in the secretory epithelium. In AR especially, staining intensity was correlated with the height of the epithelium with more intense immunoreactivity in tall segments. Since the lower epithelium has been considered inactive or resting, our results suggest a correlation between steroid-receptor expression and secretory activity. Androgens are known to upregulate the cholesterol biosynthesis, and cholesterol may be used as precursor for pheromones. Accordingly, the results of this study establish a possible link between steroid hormone action and induction of pheromone production in the apocrine axillary glands.     

Immunohistochemical localization of activated EGF receptor in human eccrine and apocrine sweat glands.

Epidermal growth factor (EGF) is secreted into sweat from secretory cells of human sweat glands. The function of EGF in sweat is poorly understood. The biological function of EGF is exerted by the binding of EGF to the receptor (EGFR) and its activation. Therefore, we immunohistochemically localized the activated form of EGFR in human eccrine and apocrine sweat glands to assess the functional importance of the EGF-EGFR system in human sweat glands. Frozen sections of human skin were stained with a monoclonal antibody (MAb) specific for tyrosine-phosphorylated (activated) EGFR and with an MAb that stains both activated and non-activated EGFR. In the secretory portion of eccrine sweat glands, nuclei of the secretory cells were stained with the anti-activated EGFR MAb. In coiled and straight portions of eccrine sweat ducts, nuclei of luminal and peripheral cells were stained with the antibody specific for activated EGFR. Luminal cell membranes and luminal cytoplasm of inner ductal cells possessed non-activated EGFR. In the secretory portion of apocrine sweat glands, activated EGFRs were present in cytoplasm and nuclei of secretory cells. These data suggest that EGF, already known to be present in the cytoplasm of secretory cells in eccrine and apocrine sweat glands, activates EGFR in the nuclei of secretory cells themselves in an intracrine manner. Because ductal cells do not express EGF, EGF in the sweat secreted from the secretory cells should activate EGFR in the ductal cells in a paracrine manner. (J Histochem Cytochem 49:597-601, 2001)     

The evolution of sweat glands

Mammals have two kinds of sweat glands, apocrine and eccrine, which provide for thermal cooling. In this paper we describe the distribution and characteristics of these glands in selected mammals, especially primates, and reject the suggested development of the eccrine gland from the apocrine gland during the Tertiary geological period. The evidence strongly suggests that the two glands, depending on the presence or absence of fur, have equal and similar functions among mammals; apocrine glands are not primitive. However, there is a unique and remarkable thermal eccrine system in humans; we suggest that this system evolved in concert with bipedalism and a smooth hairless skin.Iowa Quaternary Studies Contribution No. 47     

Immunoelectron microscopic localization of epidermal growth factor in the eccrine and apocrine sweat glands.

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.     

Morphological evidence for the innervation of apocrine sweat glands in the general hairy skin of the goat

Summary A histomorphological and histochemical study was made on the nerve supply to the apocrine sweat glands in the general hairy skin of the goat. In harmony with the previous report that the sweat glands in the goat are functionally under the control of sympathetic nervous system, the present study clearly demonstrates cholinesterase-reactive nerve fibers that closely surround the secretory portion of these glands in most of the hairy skin area, though the nerve network is fairly coarse. Analysis with cholinesterase inhibitors indicated that the sudomotor nerves in the goat contain both specific and non-specific cholinesterase.     

The ultrastructure of monkey eccrine sweat glands

Summary The ultrastructure of monkey eccrine sweat glands is described. The secretory portion of the sweat gland is discussed in detail. The morphological differences in the secretory coil using three different fixatives and fixative combinations are emphasized. The secretory product of dark cells is seen to have three distinct appearances depending upon the fixative used. The biochemical significance of the latter finding is discussed. The appearance of clear cell cytoplasmic processes is described using the different fixatives. The similarity of adjacent clear cell processes to those of avian salt glands is pointed out and discussed. Evidence is presented to indicate that dark cells arise from clear cells via an intermediate cell type. The appearance of the clear cell plasma membrane is described and the necessity for the use of the general term multilaminar plasma membrane is discussed.Supported by U.S.P.H.S. grant 5 T 1-GM-29 F-04 AS. The author would like to express his gratitude to the Lederle Laboratories and in particular to Dr.James Vickers for providing the tissue. Sincere thanks is given to Mrs.Dagmar Graham and Mrs.Ditza Springer for technical assistance and also to MissMary Lorenc for preparation of the diagram. In addition, I would like to thank Dr.J. A. G. Rhodin for his criticism and advice.     

Human axillary apocrine glands: proteins involved in the apocrine secretory mechanism

The apocrine secretory mechanism is a mode of secretion by which the apical part of the cell cytoplasm is pinched off, which leads to the formation of an aposome. The distinct mechanism of formation and decapitation of the aposome is not well investigated. Only few proteins are known that are involved in this secretory mechanism. We studied the human axillary apocrine gland and looked at proteins associated with cytokinesis, a process that is comparable to the pinching-off mechanism of apocrine glandular cells. By immunohistochemistry, we detected actin, myosin II, cytokeratin 7 and 19, α- and β-tubulin, anillin, cofilin, syntaxin 2, vamp8/endobrevin and septin 2. In highly active glandular cells, these proteins are located at the base of the apical protrusion when the aposome is in the process of being released or are concentrated in the cap of the apical protrusion. These findings demonstrate new insights on apocrine secretory mechanisms and point to similarities to the terminal step of cytokinesis, which is regulated by a SNARE-mediated membrane fusion event.     

Functional cytology of the apocrine glands of the anal sac in cats, Felis silvestris f. catus]

Apocrine glands of the anal sacs in cats (Felis silvestris f. catus) were examined by transmission and scanning electron microscopy. The secretory cells exhibit a typical equipment with organelles that varied according to the season as well as the animal's sex and state of reproduction. This can be mainly explained by seasonal differences in secretory activity. The cytological dynamics observed are, particularly, related to the smooth endoplasmic reticulum, which, for the first time, can be demonstrated in its crystalloid form in apocrine glands.     

The cytology of submandibular glands of the opossum

Tooth attachment in the majority of the bony fish is by ankylosis or fibrous membrane. However, in one group of the osteichthys, the trigger-fish or balistids, tooth attachment is by means of a periodontium composed of a shallow alveolar socket, a periodontal ligament and acellular cementum. Histologically, the balistid periodontal ligament is composed of a dense fibro-cellular connective tissue possessing an abundance of typical fibrocytes, collagen fiber bundles, and oxytalan fibers. The collagen fiber bundles which resemble the principal fiber bundles of the mammalian periodontal ligament are inserted into the bone of the shallow alveolar sockets and are anchored to the teeth by means of a layer of amorphous acellular cementum that covers the radicular dentin. No cementoblasts were found in functional teeth, and epithelial rests are lacking. The mid-central zone of the balistid periodontal ligament is occupied by small blood vessels.     

The protease corin regulates electrolyte homeostasis in eccrine sweat glands

Sweating is a basic skin function in body temperature control. In sweat glands, salt excretion and reabsorption are regulated to avoid electrolyte imbalance. To date, the mechanism underlying such regulation is not fully understood. Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), a cardiac hormone essential for normal blood volume and pressure. Here, we report an unexpected role of corin in sweat glands to promote sweat and salt excretion in regulating electrolyte homeostasis. In human and mouse eccrine sweat glands, corin and ANP are expressed in the luminal epithelial cells. In corin-deficient mice on normal- and high-salt diets, sweat and salt excretion is reduced. This phenotype is associated with enhanced epithelial sodium channel (ENaC) activity that mediates Na⁺ and water reabsorption. Treatment of amiloride, an ENaC inhibitor, normalizes sweat and salt excretion in corin-deficient mice. Moreover, treatment of aldosterone decreases sweat and salt excretion in wild-type (WT), but not corin-deficient, mice. These results reveal an important regulatory function of corin in eccrine sweat glands to promote sweat and salt excretion.

Sweating is a basic skin function in body temperature control, and salt excretion and reabsorption in sweat glands are essential for salt-water balance. This study identifies corin, a transmembrane protease that activates atrial natriuretic peptide, as a key enzyme in regulating salt excretion in the skin.     

Topiramate reduced sweat secretion and aquaporin-5 expression in sweat glands of mice

Decreased sweat secretion is a primary side effect of topiramate in pediatric patients, but the mechanism underlying this effect remains unclear. This study aimed to better understand how topiramate decreases sweat secretion by examining its effect on the expression of carbonic anhydrase (CA) II and aquaporin-5 (AQP5), total CA activity, as well as on tissue morphology of sweat glands in mice. Both developing and mature mice were treated with a low (20 mg/kg/day) and high dose (80 mg/kg/day) of topiramate for 4 weeks. Sweat secretion was investigated by an established technique of examining mold impressions of hind paws. CA II and AQP5 expression levels were determined by immunofluorescence and immunoblotting and CA activity by a colorimetric assay. In mature mice, topiramate treatment decreased the number of pilocarpine reactive sweat glands from baseline in both the low and high dose groups by 83% and 75%, respectively. A similar decrease was seen in developing mice. Mature mice with reactive sweat glands that declined more than 25% compared to baseline were defined as anhidrotic mice. These mice did not differ from controls in average secretory coil diameter, CA II expression and CA activity. In contrast, anhidrotic mice did show a reduction in membrane AQP5 expression in sweat glands after topiramate delivery. Thus, sweat secretion and membrane AQP5 expression in mouse sweat glands decreased following topiramate administration. These results suggest dysregulation of AQP5 may be involved in topiramate-induced hypohidrosis and topiramate may serve as a novel therapy for hyperhidrosis.