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Endocrine System Jack L. Haar, Ph.D. Learning objectives 1. Identify endocrine organs and cells at the light microscopic level. 2. Correlate the embryological development of the pituitary gland with its adult structure and function. 3. Describe the structure of endocrine organs. 4. Name the secretory cells in endocrine organs, identify their secretory products and explain how their secretion is regulated. I. General information A. Endocrine versus exocrine glands Exocrine Endocrine Method of product distribution Duct (usually) Ductless Site of product release Epithelial surface Intercellular Fluid or Blood Method of product release Mero-, Apo-, Holocrine Merocrine, Diffusion Site of product action Local Long distance, usually Secretory product Mucus, Lipid, Cells, Enzymes Polypeptides, Steroids Hormones Cell polarity High None (usually) B. Endocrine glands of the human body Histology of the Pituitary Gland (Hypophysis) II. Pituitary gland origins A. Stomodeal ectoderm 1. Adenohypophysis B. Evagination of diencephalon 1. Neurohypophysis III. Pituitary organization A. Located in sella turcica of sphenoid bone below hypothalamus, separated from it by diaphragm sellae through which the pituitary stalk, infundibulum passes B. Surrounded by dense connective tissue capsule C. Extensive capillary beds associated with gland D. Subdivisions: IV. Adenohypophysis A. Pars distalis 1. Structure a. Forms the majority of the pituitary gland b. Glandular appearance-cells arranged in cords, not polarized, protein secreting c. Supported by reticular fiber framework d. 2. Fenestrated capillaries Cell types a. Chromophobes i. ii. b. No secretory granules Reserve cells or degranulated cells Chromophils i. Contain secretory granules with protein hormone ii. Acidophils: granule contents have affinity for acid dyes (eosin) iii. Basophils: granule contents have affinity for basic dyes (hematoxylin) 3. Acidophils a. Smaller cells, more numerous b. Types i. Somatotropes (75%) 1) Secrete somatotropin (growth hormone, GH) 2) Hormone has sequence homology with prolactin 3) Indirectly stimulates epiphyseal plate 4) Gigantism/Dwarfism; Acromegaly 2. Mammotropes (25%) 1. Secrete prolactin 2. Stimulates milk secretion 3. Galactorrhea, continuous milk production (tumor) 4. Basophils a. Larger than acidophils b. Granules stain with PAS c. Types i. Thyrotropes 1) ii. Secrete thyroid stimulating hormone (TSH) Gonadotropes 1) 2) iii. Secrete leutinizing hormone (LH) and follicle stimulating hormone (FSH) Same cell secretes both hormones having similar structure Corticotropes 1) 2) Secrete adrenocorticotropic hormone (ACTH), lipotropin and melanocyte stimulating hormone (MSH) and endorphin Primary sequence of each hormone found within a larger precursor protein-proopiomelanocortin Hormone General Cell Type Specific Cell Type GH Prolactin TSH FSH/LH ACTH Acidophil Acidophil Basophil Basophil Basophil Somatotrope Mammotrope Thyrotrope Gonadotrope Corticotrope B. Pars Tuberalis 1. Consists of a collar of cells surrounding the infundibulum 2. Contains gonadotropes only C. Pars Intermedia (2% of the adenohypophysis) 1. Consists of cells surrounding the cystic remains of Rathke’s pouch and cells which have migrated into the pars nervosa 2. Composed of corticotropes only D. Control of adenohypophysis secretion (primarily pars distalis) IV. 1. Hypothalamic releasing or inhibitory hormones (factors) are synthesized by neurons located in the hypothalamus and are transported down the axon 2. Axons end at a capillary bed located in a brain region just above the infundibulum (median eminence) and the hypothalamic factors are secreted into this capillary bed 3. The capillary bed drains into hypophyseal portal vessels which travel down the infundibulum carrying the hypothalamic factors; portal vessels connect/end in capillaries within the pars distalis 4. Hypothalamic factors exit capillaries in the pars distalis and either stimulate or inhibit the release of hormones from the acidophils and basophils in the pars distalis 5. Negative feedback occurs at multiple levels for control Neurohypophysis A. Components 1. Infundibulum 2. a. Connects hypophysis with hypothalamus b. Composed of axons from supraoptic and paraventricular nuclei of the hypothalamus forming the hypothalamichypophyseal tract Pars nervosa a. Axons and terminals of hypothalamic-hypophyseal tract terminating in association with capillaries – Herring bodies b. Pituicytes i. ii. iii. Glial cells, highly polymorphic Also present in infundibulum In humans, may accumulate pigment granules resembling Herring bodies E. Neurohypophyseal secretion 1. Unlike the adenohypophysis, no hormone synthesis occurs in the pars nervosa, rather, the hormones (oxytocin and vasopressin) are stored in axon terminals (Herring bodies) after being synthesized in and transported from the supraoptic and paraventricular nuclei of the hypothalamus. 2. Hormones include: a. Oxytocin i. ii. b. 3. Synthesized primarily in the paraventricular nucleus Stimulates smooth muscle contraction Antidiuretic hormone (ADH/vasopressin) i. Synthesized primarily in the supraoptic nucleus ii. Increases water retention Release of hormone (neurosecretion) results from nervous activity (action potentials) in the hypothalamic neurons causing release analogous to release of neurotransmitter Endocrine Organs II Thyroid Gland I. Origin and Location II. Functions A. Synthesizes thyroxine (tetraiodothyronine, T4) and triiodothyronine (T3) for regulation of metabolic rate B. Synthesizes calcitonin, lowers blood calcium levels III. Gross Structure A. Bilobed gland connected by an isthmus anterior to the larynx B. Lobes lateral to trachea extending from thyroid cartilage to the fifth or sixth tracheal ring. C. Extensive vascular supply IV. Histology A. Composed of spherical follicles 1. Follicular or principal cells; cuboidal epithelium, however, height varies between squamous and columnar depending on activity of gland 2. Center of follicle contains colloid i. Colloid is a non-specific term used for any accumulation of proteinaceous, gelatin-like material, which in this case, refers to the material contained within the follicle, specifically, the protein thyroglobulin ii. Thyroglobulin (glycoprotein) secreted by follicle cells iii. Thyroid hormones contain modified tyrosine amino acids in the primary sequence of thyroglobulin, the entire protein complex representing a storage form of thyroid hormones 3. Fenestrated capillaries B. Parafollicular cells (C cells, clear cells) 1. Neural crest origin 2. Occur singly within follicular epithelium or in small clusters between follicles 3. Contain typical protein synthetic organelles and secretory granules, no polarity 4. In some species, but not human, is known to secrete calcitonin i. Inhibits bone resorption, lowering Ca++ levels ii. Antagonist of parathyroid hormone V. Ultrastructure of follicle cells A. Thyroid hormone synthesis and secretion involves release of larger precursor molecule (thyroglobulin) onto an epithelial surface (follicle lumen) then reuptake and cleavage of the precursor to release the hormone; organelles and their distribution in the follicle cells reflect this polarity of function, typical of exocrine glands B. Basal lamina C. Apical microvilli D. Junctional complexes E. Synthetic features and secretory features 1. Extensive smooth ER 2. Golgi 3. Transport/secretory vesicles F. Resorptive and degradative features 1. Pseudopodia to form resporption vaculoles 2. Numerous lysosomes and phagosomes VI. Histophysiology of follicle cells A. Synthesis and secretion of thyroid hormones occur in three stages 1. Synthesis, secretion and storage of thyroglobulin in the follicle lumen 2. Iodination of tyrosines on thyroglobulin in the follicle lumen and rearrangement to form thyroid hormones which remain intercalated in the primary sequence of thyroglobulin 3. Re-uptake (resorption) of iodinated thyroglobulin, hydrolysis and release of free thyroid hormones (T3 and T4) from the follicle cell B. Active and inactive follicles !. Active follicle–follicle cells are cuboidal to columnar and are involved with both secretion and resorption of thyroglobulin. 2. Inactive follicle–follicle cells are squamous, reflecting the paucity of secretory organelles and the lack of synthetic and uptake activity. C. Regulation 1. Thyroid stimulating hormone (TSH) 2. Feedback loop with pituitary and hypothalamus VII. Diseases of the Thyroid A. Hyperthyroidism (Grave’s Disease B. Hypothyroidism 1. Myxedema (adult) 2. Cretinism (childhood) C. Iodine Deficiency Goiter Parathyroid Gland General Organization and Action Embryology and Gross Anatomy Usually 2 pair (superior and inferior) located on posterior surface of thyroid gland embedded in connective tissue capsule of thyroid 6x1x2mm in size. Ellipsoid, dark tan to yellowish in color Number may vary (2-6), can be associated with thymus or isolated in the mediastinum Functions Increase blood Ca++ levels via single hormone, parathyroid hormone (Parathormone) Parathyroid hormone (PTH) acts on osteoclasts, renal tubular cells and indirectly on intestinal epithelial cells Microscopic Anatomy A. Stroma 1. Thin connective tissue capsule from which septae (trabeculae) subdivide gland into lobes 2. Various amounts of adipose cells, increasing with age; may account for 60-70% of the gland in the elderly 3. Fenestrated capillaries B. Parenchyma 1. Chief (principal) cells i. Major cell type, arranged in cords or clumps ii. Secrete PTH 2. Oxyphilic cells i. Large cells which may appear singly or in clumps ii. Heterochromatic nucleus with intensely eosinophilic cytoplasm due to large numbers of mitochondria iii. No secretory granules iv. Function unknown Adrenal Gland I. General Organization A. Cortex B. Medulla II. Cortex A. Zona glomerulosa (about 15%) 1. Located immediately beneath capsule 2. Cells appear as round clusters 3. Secretes mineralcorticoids, such as aldosterone B. Zona Fasiculata (about 80%) 1. Middle layer and largest cortical zone 2. Cells arranged in rows perpendicular to the capsule with alternating sinusoidal capillaries 3. Cells appear highly vacuolated due to presence of numerous lipid (cholesterol) droplets in the cytoplasm 4. Secretes glucocorticoids: corticosterone, cortisol, androgens and estrogens C. Zona reticularis (about 5%) 1. Occupies deepest layer of the cortex 2. Cells arranged as anastomosing cords 3. Same secretions as Zona fasciculate D. Cytological features 1. Large numbers of cytoplasmic lipid droplets 2. Large amounts of sER 3. Mitchondria with tubular cristae 4. Secretion by diffusion; no storage of products, which are released upon demand III. Adrenal Medulla A. Derived from neural crest; represents sympatheic ganglion B. Cells arranged as cords or clumps C. Chromaffin cells 1. Synthesize and release epinephrine (80%) and norepinephrine (20%) from different cell populations 2. Product stored in dense core granules with chromgranins 3. Secretion by merocrine mode 4. Innervated by sympathetic, pregangionic fibers 5. Parenchymal cells of medulla can be regarded as modified sympathetic post-ganglionic neurons Pineal Gland (Epiphysis Cerebri) Structure I. Conical-shaped gland, 5-8 mm in length and 3-5 mm in width; develops from the roof of the diencephalon and remains attached by a short pineal stalk II. Surrounded by a capsule composed of pia mater A. Connective tissue septa derived from the pia mater penetrate the gland and subdivide it into indistinct lobules. B. III. Sympathetic axons and blood vessels enter the gland with the septa. Cells A. Pinealocytes 1. Major cell type, represent modified neurons 2. Euchromatic nucleus, spherical to ovoid, with a prominent nucleolus 3. Cytoplasm not evident with conventional stains; however, silver staining reveals that the cell generally has two or more extensions similar to neuronal processes. B. 4. Processes end in association with capillaries 5. Secrete melatonin, an indoleamine hormone Interstitial cells 1. Minor cell type, similar to astrocytes in the brain 2. Nucleus is elongated and more heterochromatic than that of pinealocytes. 3. Possess long processes with intermediate filaments 4. Located among groups of pinealocytes and in the connective tissue septae IV. Corpora araneacea (brain sand) A. Globular, basophilic accumulations of calcium phosphates and carbonates in the interstitial space B. Radio-opaque and, thus, often used as indicators of midline deflection of the brain resulting from pathological conditions Secretion I. Major hormone secreted is melatonin which regulates diurnal (circadian) lightdark cycles and seasonal rhythms. II. Melatonin is secreted during darkness; secretion is inhibited by light. III. Retinal stimulation by light is relayed to the pineal via sympathetic innervation from the superior cervical ganglion. Endocrine organs laboratory You are responsible for identifying the following structures in the Digital Histology CD package. Pituitary gland (hypophysis) Adenohypophysis Pars distalis Acidophils Basophils Capillary Chromophobes Pars intermedia Basophils Colloid Remnants of Rathke's pouch Pars tuberalis Basophils Neurohypophysis Infundibulum Pars nervosa Axons Capillary Herring bodies Pituicyte Thyroid gland Capillary Colloid Follicle Active follicle Inactive follicle Follicle cells Parafollicular cell (clear cell) Secretory granules Stroma Parathyroid gland Capillary Oxyphil cell Principal cell Adrenal gland Adrenal cortex Zona fasciculata Zona glomerulosa Zona reticularis Adrenal medulla Chromaffin cell Secretory granule Capsule Capillaries Veins Pineal gland Blood vessels Capsule Connective tissue septum Interstitial cell Pia mater Pinealocyte VIRTUAL SLIDE LINKS Pituitary Thyroid Gland Adrenal Gland