Class #bo – Prof.Massimiani-Histology course Page 1 of 25 HISTOLOGY Prof. Massimiani – 16/03/2021 Tommaso Antinori-Benedetta Pascucci GLANDULAR EPITHELIA 1.1 introduction Glandular epithelia are another kind of epithelia tessue in addition to surface epithelia so epithelium not only covers body surface in lines body cavities, but also constitute this gland. So Glandular epithelium form the secretory portion, that is called the parenchyma of glands and their ducts. So the Glandular epithelia is specialized epithelium for the production and secretion of various macromolecules and because of its primary function, Glanduar epithelium is also called the secretory ephitelia. So glandular almost all cell types of the ability to synthesize and secrete molecules of various kinds. When this activity becomes the function of specialized cells with epthelial organization the ephitilium becomes secretory or glandular ephitelia. So glandular ephetilia are formed by cell specialized in the synthesis and secretion of different types of substances and constitute the secreting tissues of endocrine and exocrine glands. So they, the epithelia cell that function mainly to produce and secrete various macromolecules, may occuring in the ephitelia with other major function or comprise specialized organs called Glands in large glands the set of ephetilia cells is called parenchyma, the surrounding connective tissue is called the stroma. Glandular epithelium may synthesize and secrete proteins, lipids or carbohydrates 1.2 HOW GLANDS ORIGINATE So to understand the differences between exocrine and endocrine glands, we have to understand how glands originate. So both of the glands of endocrine and exocrine originated with the proliferation of surface epithelial cells and their down growth into the underlying connective tissue, but the exocrine glands retain their connection with surface epithelium while endocrine cells complete lose this so endocrine glands will be completely embedded into underlying connective tissue and they release their product that is called hormones, in the capillary while the exocrine glands release their product throw a duck into the surface, on the surface epithelium. Exocrine glands can be classified with respect to morphological features according to locations or where they are position and the cell number so if they are unicellular or multicellular, Shape of secretory unit that is called the adenomere and shape of excretory unit, that is called duct. 1 Class #bo – Prof.Massimiani-Histology course Page 2 of 25 1.3 location So exocrine glands, can be regarding with respect to the location, can be classified into Intra epithelia exocrine glands. So intra epithelia exocrine glands can be unicellular or multicellular and they are completely embedded into the lining epithelium tissue while the extraepithelial glands are occupied the epithelium and also the underlying connective tissue and they are always multicellular. 1.4 the cell number So regarding the cell number exocrine cells can be divided into unicellular and multicelluar. So unicellular occur singly in a sheet epithelium and the unique example of unicellular exocrine glands are the goblet cells. While multicellular consists of multiple secretory epithelial cells and they can vary in size from simple invagination of the surface epithelium two large organs. For example, pancreas. 1.5 GLOBET CELLS God bless are the unique example of unicellular exocrine glands in our body. So they are scattered among the epithelia cells of some epithelia such as the respiratory epithelium of the trachea the intestinal epithelium, so they produce mucin, that is a mixture of Glycoproteins and glycosaminoglycans 2 Class #bo – Prof.Massimiani-Histology course Page 3 of 25 so both glycosaminoglycans and glycoprotein are component of the ground substance of the connective tissue. They glycosaminoglycan are the disaccharides units repeated thousands of times while glycoproteins are formed by a sense of protein core plus oligosaccharides linked to it. So about the secretion of mucin, the protein synthesized in the rough endoplasmic reticulum as always occur, sugars are added in the Golgi apparatus. Then there is the formation of secretory vesicles, that are release from the apical part of the cells of the goblet cells by exocytosis and 3 Class #bo – Prof.Massimiani-Histology course Page 4 of 25 mucism in water form the mucus. So these are the goblet cells that are indicated with b and these are the goblet cells that are present among the epithelia cells of pseudostratified epithelium of the trachea. So, here, they release in the apical part, they release the mucin, that with the water form mucus. The mucus entrap the particles coming from the air and cilia moves this mucus. 1.6 multicellular exocrine glands The Multicellular exocrine glands, all of them are formed by Secretory epithelia cells that form the secretory portion that is called adenomere. While then, there is an excretory portion that allow the product to be release outside and this part is called Duct. So the secretory portion is this one in Orange, the doctor it is this one in purple so all the excretory cells posses this structure with 4 Class #bo – Prof.Massimiani-Histology course Page 5 of 25 duct and adenomere that can be organized in some different ways, that now we will see. So exocrine multicellular gland can be classified considering the structure of the duct and the adenomere. So epithelia of exocrine cells are organized as continuous system of many small secretory units or adenomere and the duct that transporter the secretion out of the glands. The duct can be not branched and so the glands will be called simple, and the duct can have two or more branches, and so the gland will be called compound. About the adenomere. The adenomere can be tubular. So if the adenomere is in the form of tubule will be called tubular. If the adenomere is in the shape of a grain of saclike, is called acinar or alveolar and adenomere can be also Tubulo-acinar we bought the structure, tubule and grain or saclike structure either type of secretory unit may be branching even if the duct is not branched. Okay, so now let's see some example regarding the structure of the adenomere. Tubular adenomere is typical of crypt of lieberkuhn. So These are the crypt of lieberkuhn. That are present at the base of villi, that are present in the small intestine. They possess tubular structure and for this reason they are called Simple tubular glands. They synthesized as we will see, 5 Class #bo – Prof.Massimiani-Histology course Page 6 of 25 digestive enzymes that are released in the Lumen of the intestine. So this is the gland, Then, there are Acinar adenomere. that are typical of the mammary gland So this is an acinus. That is present in the mammary gland, so mammary gland posses acinar adenomere. And then salivary glands that possess adenomere with tubular acinar structure. 6 Class #bo – Prof.Massimiani-Histology course Page 7 of 25 So this table allows you to visualize the classification of exocrine multicellular glands according to the structure of that and adenomere. So in the upper part of the table, you will see the simple gland. That means that the doctor is not Branched while in the the bottom there are the compounds glands. That means that the doctor duct is branched. The simple gland can be tubular if the adenomere is like a tube essentially and so an example is are the crypt of Lieberkuhn that we already see. Then adenomere can be tubular but coiled and example are the sweat glands. So sweat glands are present into the in the skin. So the coil tubular structure is composed of the secretory portion that is located in the dermis. Then, there is simple branched tubular so that means that the adenomere is branched and the branches are like tubes. So these glands are the mucus glands for example of the duodenum and the esophagus. Then there are the simple alveolar acinar glands that are not not found in the adult. So they are essentially stage of development of simple branching length. So they are just a stage of development of these other glands and then there are the simple branch in the alveolar. So this this means that the adenomere is branched and then branches is sulk like, an example is the sebaceous glands that produce a product that is an oily product then we will see some picture of sebaceous glands. And then there are the compound glands. That means is also the adenomere is branched and they are the compound tubular, example of compound tubular glands are for example, the mucous glands in the mouth. Then there are the compound alveolar or acinar glands. and they are the mammary glands. That posses, you can see the adenomere that is branched and the branches are sacklike. And then there are the compound tubular alveolar that some example is the salivary glands that are compound tubule alveolar exocrine glands or also excretory portion of the pancreas. 7 Class #bo – Prof.Massimiani-Histology course Page 8 of 25 1.7 CLASSIFICATION OF AN EXOCRINE GLAND ACCORDING TO TYPE OF SECRETION Exocrine gland can be classified also according the type of secretion and secretion can be divided in Mucous, Serous, Mixed secretion. So in the case of Mucous gland, these gland secrete highly glycosylated protein, then that become hydrated and so they form mucous, and we already see goblet cells but there are also sublingual salivary glands that possess mucous secretion so they produce this mixture of proteins and carbohydrates that in water form mucus Then there are the Serous glands and for example pancreas the exocrine part of the pancreas that secretes digestive enzymes. So not glycosylated proteins. and then, there are Mixed gland that possess mucus plus serous secretion. So they produce both digestive enzymes and mucous, and example is mandibular salivary glands. 1.8 Mechanisms of exocrine gland secretion Exocrine gland can be classified also according to the mechanism of secretion and there are three basic mechanism for releasing the product by exocrine gland sir. And essentially, these three basic mechanisms for releasing the product by exocrine glands, Merocrine secretion, Apocrine secretion, Holocrine secretion. Salivary Exocytosis secretory to vesicle So you can see that the merocrine secretion that is typical of the most exocrine cell, exocrine secretion usually containing protein that are secreted by exocytosis at the apical end of secretory cells, so here in this example you can see the salivary glands, that are glands that possess this merocrine secretion in which you can see the adenomere in orange, that is composed by this cells that release their product by exocytosis, so there are secretory vescicles that release their product by exocytosis, and the product is transported outside by the duct. So this is the apocrine secretion that involves loss of membrane-enclosed apical cytoplasm that contain one or more lipid droplets. So in this picture you can see apocrine secretion in which the cell of adenomere lose the apical part of the cells with this part of cytoplasm where the lipid droplets are release outside. So there is the lost of apical parts o cytoplasm and togheter with this are release also the lipid droplets, and then this droplets are release outside by the duct. 8 Class #bo – Prof.Massimiani-Histology course Page 9 of 25 The third and last kind of mechanism of secretion is the Holocrine secretion in which the release of the product contain inside the cells occurs by the disintegration of the secretory cells themself. So here adenomere that is in Orange is composed by secretory cells that completely disintegrates themselves and by this disintegration they release the the product that is contain inside them. So at the end, these cells will die by a programmed cell death. And so in this way, they released their product that is come outside by the duct and an example is the sebaceous gland of hair follicles. 9 Class #bo – Prof.Massimiani-Histology course 25 Page 10 of Okay, so these are the exocrine glands of our body. If you have to classify an exocrine glands, you had to mention the structure of the duct. So if the duct is not Branched, the gland will be simple. If the duct is Branched, the glands will be compound so for example, the sebaceous gland is simple exocrine glands because it possess an not branched duct while the salivary glands are compound because they duct is branched either then you have to look at the structure of the adenomere. So for example, salivary glands possess a tubulo acinar adenomere, so they are called tubulo acinar while the sebaceous gland possess an adenomere that is acinar and so it is defined acinar. the sweat glands for example, they possess, they are called Simple, because they possessed not branched duct and they are prosses tubular adenomere and then you have also to look at the type of mechanism of secretion. So if they possess a merocrine or apocrine, or holocrine secretion, so for example, salivary glands prossess a merocrine secretion, a sebaceous glands has an holocrine secretion, which the product the lipids, the sebum is release in holocrine way so by the completely the complete disintegration of the cell. Mammary glands for example possess both apocrine and merocrine secretion that is apocrine for the lipids component and merocrine for the protein components. So especially for the casein and so on. 10 Class #bo – Prof.Massimiani-Histology course 25 Page 11 of So now let's focus on the intestinal exocrine glands that are of three types. So there are three types of intestinal exocrine glands and they are the goblet cells, the intestinal glands or Crypts of lieberkuhn, or submucosal or brunners glands. Okay, the Goblet cells, as we already mentioned them. They are unicellular mucin secret glands, the increase in number from the duodenum to the terminal part of the ileum so they secrete mucous. That possess a protective function in the intestine. Then there are the crypts of lieberkuhn that are present in the small intestine in the colon, they possess merocrine secretion of digestive enzymes. So essentially, they secrete digestive enzymes in very important for the digestion of the food, t they extend from the muscularis mucosa to the thickness of the lamina propria, where they open into the luminal surface of the intestine at the base of the villi. Okay, so the glands are composed of a simple columnar epithelium that is continuous with the epithelium of the villi. Then there are submucosa or brunner’s glands, that are present very abundant in the duodenum. And they are branched tubular glands and are characterized by both zymogen-and mucus-secreting cells. 11 Class #bo – Prof.Massimiani-Histology course 25 Page 12 of Again crypts of lieberkuhn, This is a cross-section of the small intestine in which you can see plicae circulares and the villi. So essentially this are two villi. And here this is higher magnification you can see the crypts of lieberkuhn. They are present in the both small intestine and colon. They possess straight tubular structure, merocrine serous secretion, so they secret digestive enzymes, so peptidase, succarase, maltase, lactase ,lipase to digest the food. So they remember that the base of this villi are present multipotent stem cells. This Stem cells during each mitosis, if the one of the two daughter cells remains in the deep, that it will remain stem cell while the other differentiated migrates up to the size of the crypts and eventually into the Villus. Then there are the brunner’s gland. 12 Class #bo – Prof.Massimiani-Histology course 25 Page 13 of They are submucosal glands, they are abundant in duodenum, they are branched tubular glands. They are both zymogen-secreting and Mucus-secreting. and the product of their secretion posses very alkaline PH (8.1-9.3) because they containing neutral and alkaline glycoproteins and bicarbonate ions (important to protect the proximal small intestine by neutralizing the acidcontaining chyme and bring the intestinal contents close to the optimal pH for the pancreatic enzymes that are release in the duodenum) So is important this secretion to neutralize the acid PH. So we talked about them when we focus on the pancreas. So in this picture here, you can see the dashed lines that mark the boundary between the Villi that are present up respect to these dashed lines while the crypts of LieberKuhn are present here at the bottom of the villi so they extend to the muscularis mucosae that are present her. So remember the mucosal that is formed by the epithelial layer the underlying lamina propria and the muscularis mucosae. So this is the mucosa the crypts of LieberKuhn are present at the bottom of the Villi, so up to the muscularis mucosae. While the brunner’s glands are present under the mucosa so in the submucosa that are formed by columnar cell, and the duct of the brunner’s glands open in the Lumen of the intestinal gland is indicated by the arrow. 1.8 Exocrine glands of the mouth 13 Class #bo – Prof.Massimiani-Histology course 25 Page 14 of Now exocrine cell of the mouth so the major salivary glands. The exocrine glands of the mouth can be divided into two major salivary glands and minor salivary glands. So the major salivary glands are paired glands with long ducts that enter into the oral cavity; the major salivary glands consists of the parotid, the submandibular and the sublingual glands. the Parotid and the submandibular glands are actually located outside the oral cavity and their secretion reached the cavity by Ducts. The parotid gland is located subcutaneous below and in front of the ear, the submandibular glands is located under the floor of the mouth in the submandibular Triangle of the neck. The sublingual gland is located in the floor of the mouth anterior to the submandibular gland. While the minor salivary glands are located in the submucosa of different parts of the oral cavity at the included the lingual, Labial, buccal, molar and Palatine glands. So each salivary gland arises from the developing oral cavity epithelium so derived from epithelium as all other kind of exocrine glands. So initially the gland takes the form of a solid chords of cells that entered the mesenchyme. So the proliferation of epithelial cells eventually produces highly branched epithelia chords with tubular sense so leading to compound tubular-acinar gland. So this major salivary glands are tubular acinar glands. ( largest ) Then it is important to remember that the acinar of salivary glands contain serous cell, so protein secretion cell or can contain mucous cell so mucin secreted or both. So the frequencies of the three types of acinar are a prime characteristic by which the major salivary glands are distinguished. 14 Class #bo – Prof.Massimiani-Histology course 25 Page 15 of Okay, so about this point also about to distinguish the three major salivary glands, now I will show some histological specimen of this glands. So the first one is an histological specimen of the sublingual glands. Soblinguor Mucous Acini Nucleus More in Flattened Serous the Seoni Round nucleons (whited basal more domain Asfstained ) ttosinophilic Okay, so in a cross-section of sublingual glands. you will observe both mucus acinar that is this in withe and serous acinar units that are this stained, that are more stained, here the mucus acini predominate while the fully serous acinar units are rarely observed. So it contain both serious and mucous elements, but the mucous acinar predominate. Okay, and so you can distinguish the mucous acini and serous acinar depending essentially they staining. So the cytoplasm of the mucous cells is lighter stain than serous cells as you can see in the picture. 15 predominant Class #bo – Prof.Massimiani-Histology course 25 Page 16 of Okay, so the mucous cell have dark nucleus that is located in the basal domains and it is smaller and more flatter than that serous cells. Parotid Only serous glands GBH compound sci nor tubular glands Okay, than there is parotid. So the parotid glands that are the largest of the major salivary glands. They are composed of alveoli that containing only serous secretory cells, so in the sublingual gland secrete dominate predominate the mucous acini here there is predominance, better there are only serous acinar units. So the parotid glands are made up of serous acinar units and duct they according to the shape of their ducts and the secretory units are classified. These glands are classified as compound tubular acinar glands. So you can appreciate the serous acinar units because you can look at the site of cytoplasm of this secretory cells that is intensely stained in light purple. There are around nucleus his basal domain and the secretory granulus are at the apical domain of the secretory cells. Okay, so these are for example. Secretory granules and here more stained are the nuclei. 16 Class #bo – Prof.Massimiani-Histology course 25 Page 17 of These are picture of the parotid glands in which is easily easily recognizable the compound tubular acinar structure and also the serous secretion so you can see the cytoplasm of the secretory cells. This is intensely stain in purple. Again here you can see the secretory cells with the nucleus that was at the base and the secretory granules in the apical part. This is the duct and the cytoplasm that is intensely stained. Like the parotid glands, the submandibular glands are located outside of the oral cavity. They are located under either side of the floor of the mouth near the mandible. So the secretory components of the submandibular glands are the Acini which are of three types. So there are serous acinar in which are protein secreting cells like those of the parotid glands. Then that are this one here. Then there are the mucous acinar units that secrete mucin they are similar to those sublingual glands and then there are acini, that are called Mixed acini that contain both serous and mucous secreting cells. So in the case of the mixing acini the mucous cell are capped by serous cell called Demilunes of 17 Class #bo – Prof.Massimiani-Histology course 25 Page 18 of Giannuzzi. Submandibular Serous Mucous Mixed ( Demi tunes of Okay, the production of the salivary glands both Major and minor salivary glands the product of these glands are called saliva. So it includes the combine secretion of all the major and minor salivary glands sir. The salivary glands produce about 1L so 1200 ml of saliva at day. It has an numerous function relating to metabolic and non metabolic activity including moistening oral mucosa, moistening dry food to eat swallowing provide medium for dissolve and suspend food material that chemical stimulate bulbs, buffering the conteinets of the oral cavity because his high concentration of bicarbonate ions, digesting carbohydrates with digestive enzyme a-AMILASE which breaks the glycosidic bounds and continous to act in the esophagus and stomach. Controlling the bacterial flora of the oral cavity by the use of lysozyme that is an enzyme that lies muramic acid in some bacteria such as stafilococchi and about the composition of saliva it contains water 99% and then proteins, glycoprotein and electrolytes about the electrolytes is high potassium concentration that is approximately seven times that of that of the blood. And then also very important is the bicarbonate concentration that is three times the concentration of the blood. Moreover saliva perform also immunological function. In fact, it contains antibodies in particular IgA. 1. EXOCRINE GLANDS 1.1 Exocrine glands in the skin Exocrine glands in the skin derive from the down grove of the epidermal epithelium during development. They include the sweat glands and the sebaceous glands. The first ones produce the sweat, the second ones produce the sebum. 18 Giannotti) Class #bo – Prof.Massimiani-Histology course 25 Page 19 of Sweat glands are simple coiled tubular; they possess merocrine secretion over the entire body (except for the lips and external genitalia) or apocrine secretions, which are limited to the axilla areola and nipple of the mammary gland, skin around the anus and external genitalia; they possess serous secretion (sweat, important to regulate the body temperature). We can see that the sweat glands consist of two parts: 1) a secretory portion (adenomere, located deep in the dermis or in the upper part of the hypodermis) and of 2) a directly continuous, less coiled duct segment that leads to epidermal surface. Sebaceous glands, instead, are simple branched acinar, in fact the duct is not branched and the adenomere is branched. The branches are sac-like, they possess a holocrine mechanism of secretion, so with the complete disintegration of the adenomere secreting cells itself; they produce secretion called sebum, that contains essentially lipids. 1.2 Mammary glands Mammary glands are compound acinar or tubulo-acinar glands; they derive from modified sweat glands in the epidermis and lie in the subcutaneous tissue; they are composed by 15/20 irregular lobes separated by fibrous bands of connective tissue. These lobes radiate from the mammary papilla, or nipple, and are further subdivided into numerous lobules (so connective tissue divides mammary glands first in lobes and then in lobules; this secretory portion starts from the nipple). These kinds of glands are also abundant in adipose tissue, that is present in the dense connective tissue of the interlobular space (so between lobules). Each gland ends in a lactiferous duct that opens through a constricted orifice into the nipple. We can see a histological specimen where in blue we can see the connective tissue that divides the gland in lobes and lobules and are also visible in the acinar adenomere that possess sac-like structure, so they are acini that release the product outside through the duct. Mammary glands possess two different kinds of secretion: they can secrete protein component (casein) released by merocrine secretion and lipid component, released by apocrine secretion. 19 Class #bo – Prof.Massimiani-Histology course 25 Page 20 of In the merocrine secretion shown we can see the protein component in purple, that represents the milk, synthesized in the rough endoplasmic reticulum, packaged into the Golgi apparatus, and then released from the cell by exocytosis; In the apocrine secretion, instead, the lipid component is represented by lipid droplets free in the apical part of the cytoplasm, invested with an envelope of plasma membrane and then released from the cell. The milk is composed by most of all lipids (secreted by apocrine secretion mechanism), mineral salts, sugars (lactose), protein (casein) and antibodies, in particular IgA, abundant in the colostrum, so provide the newborn with some degree of passive immunity. 1.3 Endocrine glands Endocrine glands originate in different way from exocrine glands , in fact initially they originate by proliferation of the surface epithelia, then there is the downgrowth of the surface epithelia in two underlying connective tissue, but then, when the surface epithelia is lost, the endocrine glands remain completely embedded in the underlying connective tissue and so are formed by epithelial cell (parenchima), surrounded by connective tissue (stroma), highly vascularized and innervated by the autonomic nervous system, that stimulates the secretion and also the vascularization, important because the endocrine gland release the product directly into the bloodstream to target also the organs that are located away from the glands that produce these products,. These products are called hormones. Endocrine glands are individual cells that are scattered among the cells of epithelial lining and nonepithelial tissues like connective tissue cells, cardiomyocytes, hypothalamic neurons, adipocytes, kidney and thymus. All of them possess some endocrine secretion, so for example the adipocyte tissue secretes the hormones leptin and resistin; or the cardiomyocyte tissue produce natriuretic polypeptide hormones. 1.4 Hormones Endocrine glands are the producers of hormones, which are generally polypeptide or lipidic derived factors, that are released into the interstitial fluid (proteins released by exocytosis and lipophilic steroid by diffusion through the cell membrane for the uptake of the binding protein outside the cell. Hormones act at very low concentrations on tissue cells of target organs by modulating the functions, allowing signaling between cells. 2 SIGNALING BETWEEN CELLS Endocrine signaling involves hormone transport in the blood to target cells throughout the body; the receptor may also be on cells, close to the hormone's secreting cells or even on the secreting cell itself (paracrine and autocrine, respectively) So autocrine signaling is when the receptor is on cell targets itself, and paracrine if the receptor is on the target cell; endocrine signaling is instead when a cell targets a distant cell through the bloodstream. 20 Class #bo – Prof.Massimiani-Histology course 25 Page 21 of Growth factors (GF) and Cytokines are important chemical mediators of signaling between cells generally indirect. These two terms are often used interchangeably by scientists. Historically, the cytokines were associated with hematopoietic and immunological cells. Later it became clear that cytokines are used by all cells of the body. Cytokines are constituted by peptides, including chemokines, interferons, interleukins, lymphokines and tumor necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology); they're peptides so they cannot cross the lipid bilayer of cells to enter the cytoplasm, so they cytokines to affect the behaviour of the target cell, act through cell surface receptors. Hormonal signaling, that allow communication between cells, involves the following steps: 1)Biosynthesis of a particular hormone (generally polypeptides or lipid derived factors) 2)Storage and secretion of the hormones ( remember that proteins are released by exocytosis and that the lipids diffuse through the cell membrane) 3)Transport of the hormone to the target cells 4)Recognition of the hormone by an associated cell membrane or intracellular receptor protein ( the receptor can be on the plasma membrane or located inside the cell or inside the nucleus) 5)Relay and amplification of the received hormonal signal via a signal transduction process which lead to a cellular response. So the reaction of the target cells may be then recognized by the original hormone-producing cell, leading to a downregulation in the hormone production ( this is a negative feedback loop). 6)Breakdown of the hormone. Transport of the hormone to the target cell depends on the chemical nature of the molecule: there are certain hormones, including proteins, that are water soluble so they're transported directly in the bloodstream, and other type of hormones, including steroid and thyroid hormones, that are lipid-soluble and must be transported bound to carrier plasma glycoproteins such as thyroxinebinding globulin. Recognition of the hormone can be due to membrane receptors or can be mediated by intracellular so cytoplasmic or nuclear receptors. The membrane receptors are for water soluble molecules, like glycoproteins and in general proteic hormones such as thyroid-stimulating hormone, folliclestimulating hormone insulin and luteinizing hormone; so these hormones possess receptors on the surface of the target cell so they bind this receptor and start the signal transduction modifying the behaviour of the cell. Instead the intracellular receptors are characterizing of the lipid-soluble hormones, that are steroids, like estrogens and androgens, and thyroid hormones that pass through the cellular membrane, so in this case the receptor is located inside the cytoplasm or inside the nucleus. An example of protein surface receptor, could be the G-protein-coupled membrane receptors (GPCR), which are a major class of transmembrane receptors. In this case the first receptor is the hormone which binds to a GPCR; this binding induce a change in the conformation of the receptor and activates a signal transduction inside the cell that is mediated by G-proteins, which stimulates further enzymes like adenylate cyclase, that converts ATP in cyclic AMP (cAMP), that is the second messenger; this one activates protein kinases, triggering the response of target cell. An example of a receptor located inside the cell is instead the one of lipid soluble hormones, so the steroid and also T3 and T4 thyroid hormones, targeting specific sequences of DNA by diffusing into the cell. The hormone diffuse through plasma membrane because it is lipid soluble, so it can cross the phospholipid bilayer, and can bind to receptor located in the cytosol and the complex move into the nucleus, or enter the nucleus and bind to receptor inside the nucleus; their response elements are 21 Class #bo – Prof.Massimiani-Histology course 25 Page 22 of DNA sequences called promoters, that are bound by the complex of the steroid bound to its receptor. This binding hormone-receptor complex activates or represses genes and synthesis of specific mRNAs, which move ribosomes and there's a modification of the behaviour of the cell. 2.1 Endocrine system The entire endocrine system (and its exocrine glands) is an important body communication system that consists of a network of endocrine glands throughout the body, which makes and discharge hormones into the bloodstream, then transport them to target organs to regulate their specific activity. Endocrine glands and their functions : -parathyroid glands, that produce and secrete hormones to regulate calcium level in the body; -pineal gland, that secretes hormones that regulates the daily rhythms of the body and affect also the mood; it also produces melatonin, which regulates sleep patterns; -pituitary glands, that is the brain of the endocrine system and secrete hormones that regulates the functions of others endocrine glands; -thymus, that secrete hormones for the development of the immune system, stimulating the development of the cells that fight diseases; -thyroid gland, which produces and discharges hormones that regulate the metabolism; -pancreatic islets ( or Langherans islands) in the pancreas, that are the endocrine part of it, that is responsible for the blood-glucose balance. 2.2 Negative and positive feedback 22 Class #bo – Prof.Massimiani-Histology course 25 Page 23 of An example of negative and positive feedback mechanism, based on the release of hormones from the ovary, the hypothalamus and the anterior pituitary gland. In particular the pituitary gland is stimulated by a region of the brain called hypothalamus, and produces among others, two protein hormones called gonadotropins (FSH and LH), which act in the woman on the cells of the ovarian follicles and in men on the cells of the testis, by regulating the production of oocytes in ovary and sperm in testicle. 2.3 Histological organization of the epithelial cells of a multicellular endocrine gland While in the exocrine glands the basic histological structure are the adenomere and the excretory duct, in the endocrine glands, the epithelial cells that form the parenchima are organized in cords of cells or in groups of cells or, in the case of thyroid, into follicles, rounded structure, typical of the thyroid, and pull out their secretions, that are called hormones, directly into bloodstream. The cords and the follicles are covered with a connective capsule and are in general divided into two or more lobes. Islets or groups of cells scattered in another tissue are typical of islands of Langherans of pancreas, which constitute the endocrine component of the pancreas and are composed by group of endocrine cells within a capillary network, but the fact that they are scattered in the exocrine parenchyma classifies the endocrine pancreas as a gland consisting of group of cells; within the islands the cells form cords. In the thyroid, connective tissue divides the thyroid into lobules each of which consists of thyroid follicles. 1) Cords of cells 2) Islets or groups of cells 3)Follicles 3 EXOCRINE PANCREAS The pancreas is an elongated gland, constituted by a head, a body and a tail. It is joint to the duodeno by connective tissue; the pancreatic duct extends through the length of the gland and empties into the duodenum at the hepatopancreatic ampulla, called ampulla of Vater, through which the common bile duct from the liver and the gallbladder enters in the duodenum. Loose connective tissue forms a capsule around the gland and from it septa extend into the gland dividing it into well defined lobules, in which a stroma of loose connective tissue surrounds the parenchima units. Exocrine pancreas is a serous gland. Exocrine component synthesizes and secretes into the duodenum enzymes ,that are essential for the digestion into the intestine, for example the proteolytic peptidates (proteins), alpha-amylase (carbohydrates), lipases (lipids), the hossiribonucleases and ribonucleases (nucleic acids); while the endocrine pancreas' component synthesizes and secretes hormones like insulin and glucagon and other hormones in the blood which regulates the glucose, lipid and protein metabolism in the body. Exocrine pancreas is found throughout the organ, and within it distinct cell masses called islands of Langherans are dispersed and constitute the endocrine pancreas. Furthermore the exocrine pancreas is a serous gland, so the adenomeres are acinar or tubular-acinar in shape and are formed of simple epithelium of pyramidal serous cells (possess pyramid shape); essentially there is a system of ducts that convey the secretion 23 Class #bo – Prof.Massimiani-Histology course 25 Page 24 of in the duodenum; there is the intercalated ducts, the initial part that drain into the intralobular collecting ducts that drain into the larger interlobular ducts, which are lined by low columnar epithelium, then it directly drain into the main pancreatic duct which surround the length of the gland parallel to the long axis. Two hormones secreted by the enteroendocrine cells of the duodenum, secretin and cholecystokinin (CCK) are the principal regulators of the exocrine pancreas. They entry of the acidic chyme into the duodenum stimulating the release of these hormones into the blood (so the presence of acid in duodenum causes the release of secretin, presence of fats in duodenum cause release of cholecystokinin) 4 ENDOCRINE PANCREAS Islets of Langerhans constitute the endocrine pancreas for about 1%-2% of the volume of the human pancreas (but they're most numerous in the tail); cells are arranged in cords and are invested in a network of fenestrated capillaries. In H&E stained sections, the islets of Langerhans appear as clusters of pale-staining cells surrounded by more intensely staining pancreatic acini; it is difficult to identify specific islet cell types, but it's easier to identify small cells at the periphery of the islet, that are probably A cells, which are usually located at the periphery of islets of Langerhans and secrete glucagon. Instead B cells are the majority, they constitute the 60/70% of the islet cells and are generally located in the central portion and secrete insulin. D cells (5/10%) are also located peripherally, they secrete somatostatin, that inhibits insulin and glucagon secretion. There are also Minor islet cells, like PP cells , which secretes polypeptide P, stimulating gastric cells, inhibiting bile secretion and intestinal motility. 5 THYROID Thyroid is a particular kind of gland , because it is the only one in our body that stores the products of its secretion outside the cells, so inside the follicle. It is located anterior and inferior to the larynx, and consists in two lobes united by an isthmus. The structural and functional unit of the thyroid gland is the thyroid follicle. It is the only endocrine gland with a follicular organization. Thyroid follicles are roughly spherical compartment with a wall formed by a simple cuboidal or low columnar epithelium, the follicular epithelium, which lines the follicle lumen, which is completely filled with gel-like mass called colloid, which contains thyroglobulin, the inactive form of the thyroid hormones T3 and T4. The apical surfaces of the follicular cells are in contact with the colloid, while the basal surfaces rest on a typical basal lamina. The parenchyma is the thyroid epithelium, made up of follicular and parafollicular cells. Follicular cells (the principal components) product the thyroid hormones T3 and T4, that vary in shape and size according to the functional state of the gland; Parafollicular cells (C cells), pale staining with H&E, are solitary or small clusters of cells which lie within the follicle basal lamina, not exposed to the follicle lumen, they secrete calcitonin, a hormone which regulates calcium metabolism. Thyroid is an endocrine gland which possesses an extensive network of fenestrated capillaries. The thyroglobulin is the principal component of colloid; it is the inactive storage form of thyroid hormones and stains with both basic and acidic dyes, and is strongly PAS-positive. The thyroid is unique because it stores large amounts of its secretory product extracellularly, so inside the lumen of the follicles. Synthesis of the two major thyroid hormones, thyroxine (T4) and triiodothyronine (T3), in the thyroid follicle, follows a series of discrete steps: 1)Synthesis and secretion of thyroglobulin by exocytosis from follicular epithelial cells into the lumen of the follicle; 2)Resorption, diffusion and oxidation of iodide; 3)Iodination of thyroglobulin; 4)Formation of T3 or T4, depending on the addition of one or two iodine atoms; 5)Resorption of colloid. 24 Class #bo – Prof.Massimiani-Histology course 25 Page 25 of 6)Release of T4 and T3 from follicular cells into the circulation, where they are essential to normal metabolic rate in cells throughout the body. 25
