The skin of primates. XXX. The skin of the woolly monkey. (Lagothrix lagotricha)

The anatomical and histochemical features of the skin of the woolly monkey are intermediate between those of the Cercopithecoidea and the Pithecoidea. The animal has a prehensile tail, the glabrous, friction surface of which is similar to that of the fingers. The epidermis is heavily pigmented. The dermal vascularization is relatively well-developed and similar to that of the skin of the Cercopithecoidea. Hair follicles grow in groups of 4 to 15, as in the skin of the Pithecoidea. In the hairy skin, eccrine sweat glands occur only in the tail and genitalia. The woolly monkey, like the green monkey, possesses only acetylcholinesterase-containing nerve fibers around its eccrine sweat glands.     

The skin of primates. XL. The skin of the cottontop pinché Saguinus (=Oedipomidas) oedipus

The skin of Saguinus (= Oedipomidas) oedipus Linnaeus, is basically similar to that of the red-mantled tamarin, Saguinus (= Tamarinus) fuscicollis Spix; it has several peculiarities: (1) a circumscribed tuft of vibrissae on the ulnar aspect of the wrist; (2) an accumulation of apocrine glands over the sternum; and (3) an extensive posterior abdominal field of gigantic sebaceous glands admixed with large apocrine glands, better developed in the female. The epidermis, dermis, hair follicles, sebaceous ducts, and apocrine excretory ducts are all heavily pigmented. Hairs are arranged in linear perfect sets; the epithelial sac of quiescent follicles is devoid of glycogen and phosphorylase. Eccrine sweat glands are restricted to the volar friction surfaces and contain no glycogen. Only the coiled excretory ducts of the eccrine glands contain phosphorylase. All cutaneous nerve fibers are more reactive for acetylthan butyrylcholinesterase.     

The skin of primates. XLI. The skin of the silver marmoset—Callithrix (= Mico) Argentata

The skin of the silver marmoset, Callithrix (= Mico) argentata Linnaeus, has many outstanding characteristics. The unusually thin epidermis and dermis are generally devoid of melanotic melanocytes. The surface of the interramal gular region is peppered with small, elevated papillae; that of the corpus penis is characterized by keratinized, proximally directed hollow spines in whose cavities are organized nerve end-organs and capillary loops. Cholinesterase-reactive papillary nerve end-organs and Meissner corpuscles populate all volar friction surfaces. A highly vascular dermis and subcutaneous fat pad partially contribute to the characteristic rubicund color of the face, external ears, and anogenital region. Many body surface hairs are accompanied by the classic Haarscheibe of Pinkus. Sinus hairs are plentiful; a circumscribed vibrissa-bearing eminence is located on the ventral ulnar aspect of each wrist. Alkaline phosphatase-positive, stellate-shaped cells are found on the outer root sheath and epithelial sac of active and quiescent hairs in all cephalic regions; such cells are not argyrophilic, aurophilic, or osmiophilic. Hairs grow in linear perfect sets of 3 to 5 follicles; they do not grow singly on the cheek. Large sebaceous glands contain alkaline phosphatase in their peripheral acini; extensive fields of gigantic multilobular sebaceous glands contribute to the distinct, opaque-white color of the scrotal skin. Numbers of apocrine sweat glands are diminished in cephalic regions but one gland occurs with each hair follicle in the axilla, scrotum, suprapubic region, and ulnar eminence. Relatively avascular eccrine sweat glands are confined to the volar friction surfaces. Their secretory coils contain sporadically distributed glycogen and phosphorylase and surrounding nerves are much more reactive for acetyl- than butyrylcholinesterase.     

The skin of primates. 28. The stump-tail macaque (Macaca speciosa)

Though having some similarities to that of the rhesus monkey, the skin of the stump-tail macaque has several unique features. The epidermis has a sparse population of active melanocytes, and there is practically no pigmentation in the dermis. The dermis is rich in elastic fibers, the function of which seems to be to anchor the hair follicles and the arrectores pilorum muscles, and the superficial blood vessels. Large numbers of eccrine and apocrine sweat glands in the forehead and scalp are reminiscent of the axillary organ in the Hominioidea. The very large sebaceous glands on the face and bald forehead and scalp resemble those of man. The forehead and anterior portion of the scalp are bald in the adult but not in juvenile animals. In spite of an apparently rich pelage, these animals seem to show a trend toward nakedness.     

The skin of primates. XXXVI. The skin of the pigmy marmoset--Callithrix (Cebuella) pygmae

The pigmy marmoset — Callithrix (= Cebuella) pygmaea Spix — is the second detailed study of the members of the family Callithricidae. It is closely allied to the red-mantled tamarin — Saguinus (=Tamarinus) fuscicollis illigeri Spix — and shares some of its characteristics with both Prosimii and Anthropoidea. The epidermis and dermis contain moderate numbers of concurrent, melanotic melanocytes. The dermis is rich in elastin. Hair follicles grow in groups of three or four over the general body surface, and one apocrine gland is associated with each grouping. Arrectores pilorum muscles are well developed. On the ventral ulnar wrist are sinus hairs associated with apocrine glands. Most hair follicles have nerve end-organs around them that are reactive for acetylcholinesterase and alkaline phosphatase. There is a large aggregation of sebaceous glands in the suprapubic region. The large sebaceous glands in the eyelid, face, and external genitalia are surrounded by cholinesterasereactive nerves. Apocrine glands are found over most of the hairy skin except the brow, scalp and back; a large grouping of them is present in the sternal region. Only the secretory coils of apocrine glands in the external genitalia are invested with butyrylcholinesterase-rich nerves. Eccrine glands are confined to the volar surfaces of the pes and manus. They have dark cells with abundant glycogen and clear cells with neither glycogen nor PAS-reactive material. The nerves around the eccrine secretory coil are reactive only for acetylcholinesterase.     

Primate models to study eccrine sweating

The histochemistry and histology of the eccrine sweat gland in the rhesus monkey (Macaca mulatta) are described. The histochemical distribution and localization of enzymes and substrates are very similar to those found in the human; innervation is cholinergic. Active eccrine glands on the general body surface average 136 glands/cm². Above the thermal neutral zone (TNZ), sweating is the major avenue for heat loss and the role of panting in dissipating heat is relatively insignificant. The intrahypothalamic administration of prostaglandin E₁ (PGE₁) suppresses sweating and leads to an increase in core temperature. A linear relation is found between local sweat rates on the general body surface and clamped hypothalamic temperature. Studies also provide direct support for the concept that brain temperature and skin temperature interact additively in the control of sweating in higher primates. The functional characteristics of eccrine sweating in the patas monkey (Erythocebus) are qualitatively similar to those in the rhesus monkey. The patas monkey maintains a relatively constant rectal temperature (37.6–38.4°C) when equilibrated to a wide range of ambient temperaures of 15–40°C. Eccrine sweating is the main effector system for heat dissipation above the TNZ. We emphasize here that evaporative heat loss that is due to sweating is related to both mean skin and mean body temperature and at 40°C is 40% higher than that recorded from the rhesus monkey. These results indicate that the patas monkey, because of its high sweating capacity and other similarities with the human eccrine system, is a most appropriate animal model for comparative studies of eccrine sweat gland function in primates in general.     

Evolutionary origins of the mammary gland

Because the mammary gland has no known homologue among the extant reptiles, attempts to reconstruct its evolution must focus on evidence from living mammals. Of the numerous structures that have been hypothesized to have given rise to the mammary gland, only three remain as plausible progenitors: sebaceous glands, eccrine glands and apocrine glands. Ancestral mammary glands are usually assumed to have produced a copious watery secretion like that of human eccrine sweat glands. However, in terms of anatomy, physiology, development and topographical distribution, mammary glands are more similar to apocrine and sebaceous glands than to typical eccrine glands. Nevertheless, each of the three populations of cutaneous glands exhibit specializations unlikely to be primitive for the mammary gland. The mammary gland either predated full differentiation of mammalian cutaneous glands or, more probably, evolved as a neomorphic mosaic that combined the properties of apocrine and sebaceous glands. Consequently, ancestral, prototypic lacteal glands may have had the capacity to synthesize and secrete small amounts of organic substances, as do sebaceous and apocrine glands of living mammals.     

The skin of primates. XXXI. The skin of the black-collared tamarin (Tamarinus nigricollis)

The black-collared tamarin represents the first detailed study of a member of the family Callithricidae. Although certain features are unique, some of its characteristics resemble those of Prosimii and those of Anthropoidea. The epidermis is moderately pigmented, and the dermis contains numerous elestic fibers. Scattered melanocytes are found throughout both layers. Hair follicles grow in groups of 3 to 4 over the general body surface, including the muzzle. One apocrine gland is associated with each hair group. In the periinguinal region is a large concentration of gigantic sebaceous glands. Apocrine glands occur over the entire hairy skin. Aggregations of these glands on the ventral wrist (in conjunction with sinus hairs) and chest represent the ulnar gland and suprasternal gland, respectively. Apocrine secretory coils of the ulnar gland and external genitalia are surrounded by melanotic, dendritic melanocytes. Eccrine sweat glands are confined to the volar surfaces of the pes and manus. Cholinesterase-reactive granules are dispersed throughout the cytoplasm of the myoepithelial cells.     

Histology and cytochemistry of human skin. IX. The distribution of non-specific esterases

1. In the epidermis non-specific esterase activity outlines a strongly reactive band between the stratum granulosum and the stratum corneum. In the epidermis of the palm, there is no such esterase-rich band. 2. The outer sheath of active hair follicles has strong enzyme activity. The degenerating hair bulb in catagen follicles is very strongly reactive, and clusters of cells around the hair club in quiescent follicles are rich in enzyme activity. 3. Strong enzyme activity is found in young sebaceous cells, while decaying sebaceous cells and newly formed sebum are unreactive. Old sebum, however, is very intensely reactive. 4. Only the "dark" cells of eccrine sweat glands show a reaction; the "clear" cells are negative. 5. The cells of axillary apocrine glands abound in enzyme.     

Localization of sex steroid receptors in human skin

Sex steroid hormones are involved in regulation of skin development and functions as well as in some skin pathological events. To determine the sites of action of estrogens, androgens and progestins, studies have been performed during the recent years to accurately localize receptors for each steroid hormone in human skin. Androgen receptors (AR) have been localized in most keratinocytes in epidermis. In the dermis, AR was detected in about 10% of fibroblasts. In sebaceous glands, AR was observed in both basal cells and sebocytes. In hair follicles, AR expression was restricted to dermal papillar cells. In eccrine sweat glands, only few secretory cells were observed to express AR. Estrogen receptor (ER) alpha was poorly expressing, being restricted to sebocytes. In contrast, ERbeta was found to be highly expressed in the epidermis, sebaceous glands (basal cells and sebocytes) and eccrine sweat glands. In the hair follicle, ERbeta is widely expressed with strong nuclear staining in dermal papilla cells, inner sheath cells, matrix cells and outer sheath cells including the buldge region. Progesterone receptors (PR) staining was found in nuclei of some keratinocytes and in nuclei of basal cells and sebocytes in sebaceous glands. PR nuclear staining was also observed in dermal papilla cells of hair follicles and in eccrine sweat glands. This information on the differential localization of sex steroid receptors in human skin should be of great help for future investigation on the specific role of each steroid on skin and its appendages.     

The skin of primates. XXIX. The skin of the pigmy bushbaby (Galago demidovii)

The skin of the pigmy bushbaby (Galago demidovii), the smallest existing prosimian, is largely similar to that of the other African Lorisidae, although this animal has certain peculiar features. The very thin epidermis contains alkaline phosphatase-reactive dendritic cells which resemble those in the other bushbabies and the potto. The hair follicles of this animal are similar to those of the lesser bushbaby, while the sebaceous glands are different from those of the other bushbabies in being reactive for alkaline phosphatase. The histological and histochemical properties of the sweat glands are similar to those of the other bushbabies.     

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     

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)     

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.     

The histological and histochemical characteristics of the hepatoid circumanal glands in the dog: the features of similarity and difference with the skin glands of other types

Three types of skin glands, the derivatives of the outer root sheath of the hair follicle, have been compared, which are represented by hepatoid, sebaceous and apocrine sweat glands. There are three characteristic properties inherent to hepatoid glands, existence of a network of intercellular secretory tubules, lysis of some secretory cells during the duct formation which is not the fatty transformation and cyst formation.     

The skin of primates. XXXIX. The skin of the white-browed capuchin (Cebus albifrons)

The skin of the white-browed capuchin (Cebus albifrons), although basically similar to that of the squirrel monkey (Saimiri sciureus), contains several outstanding peculiarities: (1) both the epidermis and dermis of the general body surface are devoid of melanotic melanocytes; (2) the skin of the prehensile tail has no modified, glabrous friction surface; (3) the prehensile surface of the tail has no specialized nerve end-organs; (4) cholinesterase-positive, papillary nerve end-organs rest beneath the epidermal ridges of volar skin; and (5) both the clear cells and dark cells of the eccrine glands contain glycogen but neither shows phosphorylase activity.     

Differential expression of dipeptidyl peptidase IV in human versus cynomolgus monkey skin eccrine sweat glands

Dipeptidyl peptidase IV (DPP4) is a peptidase whose inhibition is beneficial in Type II diabetes treatment. Several evidences suggest potential implication of DPP4 in skin disorders such as psoriasis, keloids and fibrotic skin diseases where its inhibition could also be beneficial. DPP4 expression in human skin was described mainly in dermal fibroblasts and a subset of keratinocytes in the basal layer. Of importance in the perspective of preclinical experimentation, DPP4 distribution in skin of non-human primate species has not been documented. This report evidences unexpected differences between a set of human and cynomolgus monkey skin samples revealing a major expression of DPP4 in eccrine sweat glands of cynomolgus monkeys but not in humans. This represents a unique distinctive feature compared to the conserved expression of dipeptidyl peptidases 8 and 9 and potential relevant DPP4 substrates such as neuropeptide Y (NPY) and receptors (NPY-receptor 1 and Neurokinin receptor). Finally the observation that cathepsin D, an unrelated protease, shows the opposite expression compared to DPP4 (present in human but not in cynomolgus monkey eccrine sweat glands) could indicate that human eccrine sweat glands evolved a divergent protease repertoire compared to non-human primates. These unexpected differences in the eccrine sweat glands protease repertoire will need to be confirmed extending the analysis to a major number of donors but could imply possible biochemical divergences, reflecting the functional evolution of the glands and the control of their activity. Our findings also demonstrate that non-human primates studies aiming at understanding DPP4 function in skin biology are not readily translatable to human.     

HISTOLOGY AND CYTOCHEMISTRY OF HUMAN SKIN : IX. THE DISTRIBUTION OF NON-SPECIFIC ESTERASES

1. In the epidermis non-specific esterase activity outlines a strongly reactive band between the stratum granulosum and the stratum corneum. In the epidermis of the palm, there is no such esterase-rich band. 2. The outer sheath of active hair follicles has strong enzyme activity. The degenerating hair bulb in catagen follicles is very strongly reactive, and clusters of cells around the hair club in quiescent follicles are rich in enzyme activity. 3. Strong enzyme activity is found in young sebaceous cells, while decaying sebaceous cells and newly formed sebum are unreactive. Old sebum, however, is very intensely reactive. 4. Only the "dark" cells of eccrine sweat glands show a reaction; the "clear" cells are negative. 5. The cells of axillary apocrine glands abound in enzyme.     

Immunohistologic studies of the distribution of proliferative compartments in the appendages of adult human skin

Both, calmodulin (CaM) as well as the antigen Ki67 show a close relationship to cell proliferation. By means of specific antibodies against them, it has become possible to study the spatial distribution of proliferative compartments in tissues. We performed an indirect immunofluorescence study on unfixed frozen sections of human adult skin to gain more informations about the spatial distribution of immunoreactive CaM and Ki67 in skin appendages, i.e. anagen hair follicle, sebaceous and eccrine sweat gland. Two major patterns of immunoreactivity were seen: Type (1) or epidermis-like, which was present in the interfollicular epidermis and the pilosebaceous unit. Type (2) or sweat gland type, which was seen in eccrine sweat glands. Both types disclosed significant differences in the relative number of proliferative cells in S-phase, which might be a consequence of a quiet different tissue architecture. Furthermore, myoepithelial cells of secretory coils were likely to represent mainly SQ-cells. Their immunoreactivity in human skin was quiet different from other parts of eccrine sweat glands suggesting another ontogenetic pathway.     

Dermal cylindroma. Expression of intermediate filaments, epithelial and neuroectodermal antigens.

We report on immunohistochemical staining patterns in so-called apocrine tumors of skin with special emphasis on the dermal cylindroma. The results were compared with apocrine tubular adenoma, syringocystadenoma papilliferum and the normal eccrine sweat gland. A relationship of dermal cylindroma to the apocrine gland is suggested by expression of lysozyme and alpha 1-antichymotrypsin. The tumor shares keratin, epithelial membrane antigen (EMA) and EGF-receptor expression with eccrine and apocrine glands. The presence of intermingled cells with a coexpression of keratin and vimentin argues for a partial myoepithelia-like differentiation. Neuroectodermal antigens are missing. Therefore, dermal cylindroma is classified as an adnexal tumor of skin with a variable rate of cells of apocrine secretory, myoepithelial and undifferentiated phenotypes.