Lesson 24 - Endocrine System I SGL (notes).pdf

Cytology and Histology LESSON 24 ENDOCRINE SYSTEM (I) INTRODUCTION The endocrine system is characterised by presenting secretory epithelial cells that release their secretion products, hormones, into the circulatory system through the intercellular or perivascular spaces. These hormones circulate...

Cytology and Histology LESSON 24 ENDOCRINE SYSTEM (I) INTRODUCTION The endocrine system is characterised by presenting secretory epithelial cells that release their secretion products, hormones, into the circulatory system through the intercellular or perivascular spaces. These hormones circulate through the bloodstream until they reach their target organ, where they will take effect. The nervous and endocrine systems function differently, but both interact to modulate and coordinate the body's metabolic activity by maintaining a stable physiological state, called homeostasis. The endocrine system comprises the endocrine glands themselves (organs) and groups of cells (pancreatic islets, theca cells and corpus luteum of the ovary, interstitial cells of the testis) or isolated cells (APUD system) that are part of non-endocrine organs. The endocrine organs are hypophysis, thyroid, parathyroid, adrenal and pineal glands. In general, the endocrine organs are composed of groups of secretory epithelial cells delimited by a scarce highly vascularized fibrous stroma (capillaries), reflecting the high metabolic activity and its secretion pathway. With the exception of the follicular epithelial cells of the thyroid gland, endocrine cells organize themselves into cords and cell nests. Hormones can be of three types depending on their composition: a) Proteins and polypeptides (insulin, glucagon, etc.); b) derived from amino acids (tyrosine, catecholamines), and; c) derived from steroids and fatty acids (progesterone, estradiol and testosterone). Endocrine cells that secrete polypeptide hormones and catecholamines often have a pale, finely granular eosinophilic cytoplasm due to the presence of secretory granules and microvesicles. Endocrine cells that secrete steroid hormones have an eosinophilic cytoplasm with a foamy appearance due to the presence of lipid vacuoles. HYPOPHYSIS The hypophysis or pituitary gland is an endocrine gland that is involved in the regulation of important functions for the animal body, such as metabolism, growth and reproduction. It is located below the hypothalamus, with which it is connected by a stem or pedicle (it "hangs" from the floor of the diencephalon). This gland is located in a central depression of the sphenoid bone, called the pituitary or hypophyseal fossa of the sella turcica, and is separated from the encephalic mass by a folding of the dura mater, diaphragma sellae, which fuses with the periosteum of the bone. Its anatomical structure and its structural composition differ according to the animal species. - It measures 1 to 2 cm, depending on the species, and varies in each species with age. - It is shaped like a sac and is made up of two structures of different embryological origin separated from each other by a capsule of fibrous connective tissue (Figure 1). The neurohypophysis or posterior lobe derives from the neuroectoderm. The adenohypophysis or anterior lobe derives from the oral ectoderm (Rathke's pouch) (Figure 1). Cytology and Histology Optic chiasm Figure 1.- Diagram of the pituitary gland 1. ADENOHYPOPHYSIS OR ANTERIOR PITUITARY GLAND (Figure 1) The adenohypophysis is an endocrine gland made up of cords of cells and presents three parts: 1) Pars distalis, 2) Pars intermedia, and 3) Pars tuberalis (Figure 1). Hormonal secretion from the adenohypophysis is regulated by the hypothalamus, which, in turn, is under the influence of nervous stimuli from higher centres of the central nervous system. The secretory activity of the adenohypophysis depends on the activation of its cells by hypothalamic releasing factors. These factors are produced by the neurons of the median eminence and transported by their axons to the external zone of the median eminence (neurohypophysis), where they are released into the capillaries of the pituitary portal system, thereby passing through the bloodstream to the adenohypophysis. 1) Pars distalis of the adenohypophysis It is the most voluminous part of the entire gland (Figure 2). It has a fibrous capsule, and cords of epithelial cells surrounded by reticulin fibres and placed between the capillaries of the secondary plexus. There is very little connective tissue around the smaller vessels. Sinusoidal capillaries have a fenestrated endothelium. The classification of cells in the distal part of the adenohypophysis is as follows: a) With histochemical techniques: chromophils (they stain with acidic and basic dyes, acidophils and basophils, respectively) and chromophobes (they do not stain with acidic and basic dyes). b) With immunohistochemical techniques: • Cells expressing GH (growth hormone) • Cells expressing PRL (prolactin) • Cells expressing ACTH (corticotropic hormone) • Cells with gonadotropin expression (LH: luteinizing hormone; FSH: follicle-stimulating hormone) • Cells expressing TSH (thyrotropic hormone) • Cells with expression of S100 protein and cytokeratins Cytology and Histology The ultrastructural characteristics of the cells that produce the pituitary hormones are very similar since they are protein hormones and, therefore, their organoids conform to the Palade scheme (RER, Golgi complex and electron dense secretion granules). GH cells (Figure 2) are the most stable cell type in terms of number, granular content and structure of the cells that make up the distal part. They have other names such as STH or somatotropin-producing cells or simply somatotropin cells. They have a spherical or ovoid shape, elongated or columnar, with a size between 11 and 14 µm, and are distributed throughout the gland in small groups or palisades or, sometimes, isolated. They predominate in the lateral portions of the gland and represent 35-45% of the total cells, while in small ruminants it is 15-20%. GH cells are acidophilic. In general, the rough endoplasmic reticulum (RER) is made up of parallel cisterns, sometimes slightly dilated. When the cells show signs of functional activity, the secretory granules are fewer and smaller, while the RER and the Golgi complex are more developed. Moderately electron dense lysosomes occur in small numbers, and with an approximate size of 400-500 nm. The Golgi complex has a juxtanuclear location, with frequent images of granule formation and its development, like that of RER, is conditioned by the functional state of the cell. Electron-dense, spherical, or ovoid secretory granules are distributed throughout the cytoplasm, with a tendency to accumulate at the pole opposite the nucleus. Its size is homogeneous, with an average between 300-400 nm. Hypothalamic growth hormone releasing hormone or GHRH stimulates and somatostatin inhibits GH secretion. The GH hormone has anabolic activity as a stimulant of cell division, protein synthesis, growth and galactopoiesis in ruminants. A B Figure 2.- GH cells (A) and PRL cells (B) of the distal part of the adenohypophysis PRL cells are also known as mamotropes and lactotropes (Figure 2). They represent 35% to 50% of the cells in the distal part of the adenohypophysis, their number increases to 60% during lactation and decreases after weaning. They have diffuse distribution, forming groups or palisades, variable shape, from spherical to polyhedral, and size from 12 to 14 µm. They are acidophilic cells. The RER and the Golgi complex have no special features. In contrast, the secretory granules of typical PRL cells are the largest in adenohypophyseal cells, spherical in shape and highly electrodense. Their average size is between 375-450 nm in diameter, although they can reach 600 nm. PRL secretion is influenced by both external factors (nipple sucking, temperature, light stimuli) and internal factors (metabolic and nutritional status and phase of the reproductive cycle). Prolactinemia levels are regulated by the hypothalamic hormone that stimulates the production of PRL (prolactin releasing hormone, PRH) and the hormone that inhibits it (prolactin “release” inhibitory factor, PIF or PRIF). PRL acts on the mammary gland by controlling milk production. Cytology and Histology ACTH cells have basophilic staining and they are also called corticotropin cells. They represent 7% to 10% of the cells in the distal part of the adenohypophysis, have a homogeneous distribution, predominantly antero-medial, variable shape, from spherical to stellate, and a size of 12 to 15 µm. Ultrastructurally (Figure 3) they have a very abundant RER that can take the form of a fingerprint and thus allow them to be identified. The Golgi complex is well developed, and secretory granules are sparse, medium in size (200-300 nm), of homogeneous electron density, and tend to be concentrated at the periphery of the cell. ACTH secretion is stimulated by hypothalamic corticotropin releasing hormone (CRH). ACTH stimulates the secretion of hormones from the adrenal cortex (cortisol and androgens). A B C Figure 3.- ACTH cells (A) and LH and FSH cells (B and C) of the distal part of the adenohypophysis. LH and FSH cells are also called gonadotropic cells. They represent 10% of the cells in the distal part of the adenohypophysis and predominate in the peripheral and rostral areas of the distal part of the adenohypophysis. They are rounded or elongated with an eccentric nucleus, they measure 12 to 15 µm and are basophilic. Ultrastructurally (Figure 4), an important characteristic of this cell type is the polarity of the secretion granules, spherical, electron-dense and of different size with mean values between 200 and 400 nm. The RER is well developed and consists of cisternae of perinuclear location or widely distributed throughout the cytoplasm, often dilated with homogeneous low-density content. The Golgi complex, juxtanuclear in location, is well developed and consists of dilated sacs and small vesicles. Large lysosomes are also observed, between 1-1.5 µm in diameter. The gonadotropins LH and FSH control reproductive function, and their secretion is stimulated by hypothalamic gonadotropin releasing hormone (GnRH) and inhibited by oestrogens and testosterone (LH) and oestrogens and inhibin (FSH). TSH cells, also called thyrotropes, are basophilic cells, scarce (5%) and distributed throughout the distal part, predominantly in the anterior and medioventral portion where they generally appear isolated or in small groups. They have irregular or angular morphology and measure 12-14 µm. Its secretion granules are the smallest of all adenohypophyseal cells, with a maximum diameter of 150 nm, and are delimited by a clear halo of different density depending on the species. The RER is well developed and is arranged in the form of parallel cisterns located at one pole of the cell, or they are dilated and abundant in ribosomes. The Golgi complex, in general, is well developed. Lysosomes are larger than secretory granules (250-500 nm). Thyrotropic cells produce thyroid-stimulating hormone under the stimulating influence of hypothalamic thyrotropin releasing hormone (TRH). Cytology and Histology Follicle-stellate cells are 8 to 10 µm cells that do not stain with the usual dyes but are seen with markers such as the S100 protein and cytokeratins (Figure 5) as stellate-shaped cells with processes located between the secretory cells. Ultrastructurally, they have few organoids (RER, SER, lipid droplets, polyribosomes and glycogen). Its function is to support and maintain the hydroelectrolytic medium (Figure 4). With age, these cells join together through desmosomes, and form aggregates in the central portion of the secretory cell cords that delimit small lumens called follicular cavities. A B Figure 4.- Follicle-stellate cells of the distal part of the adenohypophysis under the light microscope stained with cytokeratins (A) and under the electron microscope (B). 2) Pars intermedia of the anterior pituitary gland This portion is adjacent to the neurohypophysis and is delimited from it by a discontinuous sheath of connective tissue. Immunohistochemical techniques identify two types of cells: cells that express melanocyte-stimulating hormone (MSH) and cells that express cytokeratins (epithelial cells). MSH cells are 12-15 µm in size. They form cords, are spherical or ovoid and basophilic. They are located close to follicular cavities with colloid. They synthesize the melanocyte stimulating hormone (MSH) and in some species of animals, beta LPH. Ultrastructurally they have RER, Golgi complex, secretory granules and lysosomes without particular characteristics. The epithelial cells line the pituitary cleft, a remnant of Rathke's pouch. It does not exist in Equidae. 3) Pars tuberalis of the adenohypophysis It is made up of longitudinal cords of basophilic, cuboidal or columnar cells between fenestrated capillaries. The cytoplasm contains some dense granules, lipid droplets, colloid droplets, and glycogen. They do not secrete any hormones, although they sometimes contain LH or FSH. 2. NEUROHYPOPHYSIS The neurohypophysis is a dependency of the endocrine neural tube. It has three parts: (1) the median eminence, continuation of the hypothalamus, (2) the infundibulum or infundibular stalk, and (3) the pars nervosa or neural lobe (Figure 6). The hormones of the neurohypophysis are produced by neurons found in the hypothalamic median eminence, forming two nuclei, the supraoptic and the paraventricular, and reach the pituitary portal system through the axons of these neurons, which discharge the secretion product into the perivascular space in the pars nervosa after passing through the infundibular stalk. Cytology and Histology Median eminence Infundibular stalk Neural lobe ADENOHYPOPHYSIS Connective Tissue Figure 5.- Diagram neurohypophysis. of the parts of the The image of the neurohypophysis with the HE technique is similar to that of the neuropil: acidophilic background (axons and cytoplasmic processes of the pituicytes) with nuclei (of the pituicytes) (Figure 6). A B C Figure 6.- Images of the neurohypophysis stained with haematoxylin and eosin (A) and with Gomori chromic eosin haematoxylin (B). Schematic of Herring bodies in an axon (C). By means of specific techniques such as Gomori haematoxylin-phloxin-chromic and that of alum with haematoxylin, the parenchyma has light blue dyes, and in its core there are thick lumps stained with intense blue, called Herring bodies (Figure 6). These bodies are arranged in isolation or in clusters close to vascular endings. The axons that run through the neurohypophyseal parenchyma present along their path lateral dilatations that are storage areas for the secretion granules of ADH and oxytocin and correspond to Herring bodies. The axons end in the synaptic bulb, and they do so as a dilatation related to the capillary walls (Figure 6). Inside, clear vesicles of nerve transmission mediators are located, but above all secretion granules are found, which end up secreting their content into the extracapillary spaces. The pituicytes are distributed throughout the neurohypophysis and present diverse morphology, predominantly similar to that of fibrous astrocytes (star shape). They are related to each other like a stellate reticulum between axons. Although a clear interaction between axons and pituicytes in neurosecretion processes is not known, they do seem to contribute to their metabolism. 1