Detection of Hepatoid Glands and Distinctive Features of the Hepatoid Acinus

In the 1920s–1930s, skin glands of a new type, hepatoid glands, were described in 13 mammal species (Rodentia, Canidae, and Bovidae). The hepatoid glands resemble sebaceous glands in their morphology, bur radically differ from them in specific structure of the acinus and another type of secretion. Later, these data either could not be confirmed or were considered insignificant and the hepatoid glands were described as modified sebaceous glands, glands with uncertain function, or modifications of epidermis. Based on the studies of various hepatoid glands in 22 species of Carniviora and Artiodactyla, the authors described in detail the characteristic features of the hepatoid acinus, which allow a precise discrimination of hepatoid and sebaceous glands. Extracellular secretory canaliculi have been described in the hepatoid glands, as well as the richness of hepatoid glands in protein, distribution of hydrophobic lipids in certain hepatoid glands, and formation of excretory ducts and cysts. The hepatoid glands are a source of great amounts of protein secreted in the merocrine way; the secretory substance of some of these glands has a strong odor.     

Once More about Hepatoid Circumanal Glands of Dogs; History of Their Discovery and Causes of Revision of Their Structure and Function

In the skin surrounding the anus in dogs and other Canidae, there is a glandular sheet consisting of strongly developed hepatoid glands, as well as single apocrine glands and a certain number of sebaceous glands, which are much smaller and occur less frequently than the hepatoid glands. All three circumanal glands have excretory ducts connecting with the hair bags (hair funnels). The hepatoid glands of some Canidae and Bovidae were extensively studied in the 1920s–1930s, but from the beginning of the 1950s until the present, as a result of the often repeated mistake passing from one book to another, old information about the hepatoid glands was fully lost, while the new information does not answer the question about the function of this complex and well developed structure. We were successful in repeating the data of the discoverers of the hepatoid glands and proved that these glands are exocrine and that their cells excrete protein to intercellular channels and then to ducts and hair funnels. According to the published data, the odor of the secretory substance of the circumanal hepatoid glands is essential for communication in wolves and dogs.     

A histological study of cutaneous glands in the brown brocket deer

We examined the histological structure of 8 skin areas thought to contain cutaneous glands of potential importance in scent communication in 16 brown brocket deerMazama gouazoubira Fisher, 1814, using standard histological techniques. Frontal areas and preorbital sacs had scant glandular development. Sebaceous gland development was prominent in vestibular nasal glands and prepucial glands. Apocrine sudoriferous glands and sebaceous glands were well developed in tarsal glands, the caudal skin area and the interdigital glands of front and hind feet. The tail had a unique arrangement of apocrine sudoriferous glands. Anal glands had moderate glandular development, and metatarsal glands were absent. Several of these glandular areas may be important in the chemical communication among brocket deer.     

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 morphogenesis of mammalian cutaneous glands in evolutionary perspective

The morphogenesis of mammalian cutaneous glands is considered based on the analysis of the literature and our own original data with the focus on the issues of gland polymorphism and specific features in postnatal development (from the case study of circumanal hepatoid glands of newborn domestic dogs), including the features reflecting the evolutionary relationships of various types of cutaneous glands. The hepatoid glands are a component of the glandular complex of the hair follicle, which also includes sebaceous and sweat glands; have a specific structure; and produce protein secretion by a merocrine pathway. Characteristic of these glands are wide polymorphism, sex- and age-related differences in the degree of development, occurrence in only a few phylogenetically related mammalian taxa (even-toed ungulates and carnivores); and a signaling type of their secretion. The data support the “generative concept,” relying on the idea of a separate and independent origination of diverse derivatives of the external integuments.     

The Tail Gland of Canids

The tail gland of canids is a hepatoid glandular organ surrounded and penetrated by powerful hair erector muscles squeezing out its lipoprotein secretion onto the skin surface. The gland is most developed in solitary species (Arctic, red, and corsac foxes) where it is represented by powerful glandular layer with large secretion containers—cisterns. It is less developed in the jackal; there are cisterns but glandular lobes do not merge into a layer. In the raccoon dog, wolf, and domestic dog the gland is composed of small lobes without cisterns. Hepatoid glands of the tail gland are represented by two histological variants distinguished by the presence or absence of hydrophobic lipids in the secretory cells. The excretory ducts are formed by lipid transformation of the cellular bands.     

Contradictions in Modern Data on the Structure and Function of Dog Hepatoid Circumanal Glands1

Since the 1950s, an erroneous viewpoint has gained a foothold in the special and reference literature that dog hepatoid circumanal glands have an abortive nature, lack efferent ducts, and show no signs of secretory activity. Nevertheless, most modern researchers indicate that these glands are actively functioning structures differentiated to exercise some function according to their histological pattern; however, no one has managed to define this function. The latest international publication (Atoji et al., 1998) considers dog circumanal hepatoid glands as a circumanal body similar to epidermis rather than glands. We discuss strong and weak points of the data on dog hepatoid circumanal glands published in 1950s–1990s in comparison with those obtained in our purposeful long-term investigation of various hepatoid glands. We strongly disagree with the viewpoint of Atoji et al. (1998); hepatoid circumanal glands of dog and other canids should be considered as odor glands, their abundant protein secretion covers the skin surface in the circumanal region, it is preserved on fecal marks, and its smell is perceived during mutual nosing of the anal region.     

Development and homeostasis of the sebaceous gland

The important role of epidermal appendages especially the sebaceous gland has only recently been recognized. In particular, it has been convincingly shown that normal development and maintenance of the sebaceous gland are required for skin homeostasis since atrophic sebaceous glands and disturbances in sebaceous lipid composition result in major defects of the physiological barrier and maintenance of the skin. Consequently, it is important to unravel the signaling network controlling proper sebaceous lineage differentiation in mammalian skin and to understand the underlying mechanisms leading to severe skin diseases, including abnormal proliferation and differentiation of the gland, defects of the lipid metabolism and barrier, as well as sebaceous tumor formation. Over the last years, results from transgenic and knock out mouse models manipulating distinct signaling pathways in the skin as well as the detailed analysis of human sebaceous gland-derived cell lines provided new insights into crucial mediators balancing proliferation and differentiation of the sebaceous gland. Here, we discuss our current knowledge of in vivo mechanisms of sebaceous gland development, maintenance and disorders and highlight recent contributions to the field of sebaceous gland biology.     

CHALONE CONTROL OF MITOTIC ACTIVITY IN SEBACEOUS GLANDS

Extracts of skin with sebaceous glands contain a substance which inhibits mitotic activity in sebaceous glands both in vivo and in vitro. This substance is neither the epidermal chalone nor the melanocyte chalone, both of which are also present in skin extracts. However, it resembles these other chalones in that it is water soluble, is precipitated by ethanol, is activated by the two stress hormones adrenalin and hydrocortisone, and is not species specific. It is present within the sebaceous glands, and it is evidently a sebaceous gland chalone.     

The anal scent sacs of the otter (Lutra Intra)

This paper describes the structure of the otter anal scent sacs. The deposited secretion contains apocrine gland protein and polymucosaccharide and sebaceous gland lipid. Chemical analyses by gas-liquid chromatography and acrylamide gel electrophoresis revealed individual differences in the composition of secretion. The individual differences in protein bands as revealed by electrophoresis were stable with time and may be useful in following the movements of wild otters in the field.
A captive pair of otters produced deposits of secretion with a periodicity similar to that of the female oestrous cycle, with both sexes producing deposits around oestrus.     

Steroid utilization by amphibian skin

Summary Portions of frog skin from different regions were examined histochemically for hydroxysteroid dehydrogenase activity. Two basic gland types were seen — those possessing activity, thought to be the poison glands, and the mucous glands which were unable to utilize the hydroxysteroids.     

Comparative responsiveness of supracaudal and other sebaceous glands in male and female guinea pigs to hormones

Different types of sebaceous glands in guinea pigs were chosen to study their comparative responsiveness to steroid hormones. Glands selected were (1) Sebaceous glands associated with rudimentary hair in the supracaudal gland; (2) Free sebaceous glands of the nipple; (3) Sebaceous glands associated with the hair. The results showed distinct differences in sensitivity among these different sebaceous glands and according to the sex of the experimental animal. The most responsive of the glands in males was the supracaudal gland; in the female the most responsive glands were the sebaceous glands of the nipple. Sebaceous glands associated with normal hair were relatively insensitive to changes in hormonal level. In all cases testosterone propionate was more potent in stimulating any of the sebaceous glands than progesterone. After gonadectomy, various sebaceous glands showed unequal states of depletion due to the different rates of differentiation and disintegration of their cells into sebum.     

Histomorphology of preorbital gland in territorial and non-territorial male blackbuck Antelope cervicapra, a critically endangered species

The preorbital gland is a specialized dermal gland of antelopes which plays an important role in territorial marking behavior and pheromonal communication. To our knowledge, there is little information available on the role of preorbital gland marks in Indian antelopes (blackbucks). Males are seen averting the gland during behavioural display and territorial marking but the functional aspect of this gland has not been examined. Hence, the aim of this study was to describe the histomorphology of the preorbital gland in territorial and non-territorial male blackbucks to determine its morphology and secretory function. The results showed that the preorbital gland is composed of modified sebaceous and apocrine glands. The apocrine gland is lined by simple cuboidal epithelial cells; the serous parts of the secretory products are often seen in the apical portions of the cells. The myoepithelial cells contain actin filaments lying on the basal membranes of the apocrine gland. There are some considerable histological changes in the presence of the sebaceous and apocrine glands in territorial males in comparison to non-territorial males. The following histological changes associated with occurrence of the sebaceous and apocrine glands have been observed in territorial and non-territorial male blackbucks: (1) increase of size of sebaceous and apocrine glands and (2) increase in density of sebaceous and apocrine glands in territorial males compared to non-territorial males. It is suggested that the higher development (i.e., size) and density of sebaceous and apocrine glands in territorial males could depend on hormone production (i.e., testosterone). Based on the histological observation and the role of sebaceous and apocrine glands in the preorbital gland supported by literature, it is possible to conclude that both territorial and non-territorial blackbuck males may produce pheromonal substances through preorbital gland (secretion) for olfactory communication.     

Cidea Control of Lipid Storage and Secretion in Mouse and Human Sebaceous Glands

Sebaceous glands are skin appendages that secrete sebum onto hair follicles to lubricate the hair and maintain skin homeostasis. In this study, we demonstrated that Cidea is expressed at high levels in lipid-laden mature sebocytes and that Cidea deficiency led to dry hair and hair loss in aged mice. In addition, Cidea-deficient mice had markedly reduced levels of skin surface lipids, including triacylglycerides (TAGs) and wax diesters (WDEs), and these mice were defective in water repulsion and thermoregulation. Furthermore, we observed that Cidea-deficient sebocytes accumulated a large number of smaller-sized lipid droplets (LDs), whereas overexpression of Cidea in human SZ95 sebocytes resulted in increased lipid storage and the accumulation of large LDs. Importantly, Cidea was highly expressed in human sebaceous glands, and its expression levels were positively correlated with human sebum secretion. Our data revealed that Cidea is a crucial regulator of sebaceous gland lipid storage and sebum lipid secretion in mammals and humans.     

Comparative Morphological Analysis of Different Hepatoid Glands: Histological Variants and the Morphofunctional Unit

Three groups can be recognized among hepatoid glands: glands synthesizing protein alone, glands synthesizing protein and hydrophobic lipids and/or melanin, and intermediate glands. Histological variants (seven in total) can be recognized within each group. Different possible combinations of hepatoid glands with other derivatives of hair follicles are considered. The first definition of the morphofunctional unit of hepatoid glands is proposed.__________Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 4, 2005, pp. 428–434.Original Russian Text Copyright © 2005 by Shabadash, Zelikina.     

Smad7-induced beta-catenin degradation alters epidermal appendage development

To assess whether Smad signaling affects skin development, we generated transgenic mice in which a Smad antagonist, Smad7, was induced in keratinocytes, including epidermal stem cells. Smad7 transgene induction perturbed hair follicle morphogenesis and differentiation, but accelerated sebaceous gland morphogenesis. Further analysis revealed that independent of its role in anti-Smad signaling, Smad7 bound beta-catenin and induced beta-catenin degradation by recruiting an E3 ligase, Smurf2, to the Smad7/beta-catenin complex. Consequently, Wnt/beta-catenin signaling was suppressed in Smad7 transgenic hair follicles. Coexpression of the Smurf2 and Smad7 transgenes exacerbated Smad7-induced abnormalities in hair follicles and sebaceous glands. Conversely, when endogenous Smad7 was knocked down, keratinocytes exhibited increased beta-catenin protein and enhanced Wnt signaling. Our data reveal a mechanism for Smad7 in antagonizing Wnt/beta-catenin signaling, thereby shifting the skin differentiation program from forming hair follicles to sebaceous glands.     

The evolution and distribution of hydroxysteroid dehydrogenase activity in human foetal skin throughout gestation

Synopsis Specimens of skin from human foetuses from 6–41 weeks gestation were incubated to demonstrate the presence of hydroxysteroid dehydrogenases (HSDs) by histochemical methods. When present HSDs were noted only within the acini of the sebaceous glands and in the secretory duct. Seventeen--HSD activity was first demonstrated at 16 weeks gestation, co-incident with full function in the glands. Three-- and 16-HSD activity did not appear until 22–24 weeks. There were differences between the foetal pattern of distribution of the enzymes within gland acini and that already known in skin from subjects in extrauterine life. The time of changeover to the latter pattern has been established as 38 weeks gestation. No correlation was noted between HSD activity and the sex of the foetus or body site. It is concluded that foetal skin is involved in steroid metabolism, and possible physiological roles for this activity are discussed, with speculation over skin as an excretory route or detoxication centre for steroids and the role of steroid metabolic activity in the local stimulation and functional control of foetal sebaceous glands.     

Jugulo-sternal-gland tumors in male tree shrews (Tupaia belangeri).

Adenocarcinomas of the jugulo-sternal glands were observed in seven adult male tree shrews (Tupaia belangeri) at biopsy or necrospy. Five of these tumors were classified as carcinomas of the sebaceous gland compartment; one was diagnosed as a papilliform adenoma of apocrine (monoptychic) sweat glands; and one was of a mixed sebaceous gland/apocrine sweat gland structure. Four sebaceous gland carcinomas had histologic evidence of vascular invasion; one had metastasized to the regional lymph nodes and lungs and had also invaded the thoracic muscles.     

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.