Histology of the and Notes 1

Lecture notes: Histology of the Pituitary Gland and Endocrine System

1. Describe the structural organization of endocrine glands

2. Define the components of the endocrine system

3. Compare and contrast the cellular composition of the adenohypophysis () and neurohypophysis ( gland)

4. Describe the hypophyseal portal system and its physiological significance

5. Compare and contrast the cellular composition of the and

6. Describe the organization and cellular features of the gland and parathyroid glands and the their cells produce

7. Explain the structural features and functions of the

8. Bone as an endocrine organ

9. Define the diffuse neuro-endocrine system

Histology of the Pituitary Gland and Endocrine System Notes 2

HISTOLOGY OF ENDOCRINE GLANDS

1. Describe the structural organization of endocrine glands The endocrine system is a collection of glands that secrete hormones, molecules that transmit chemical messages.

Hormones are capillary released to the

bloodstream and act secretory c on cells that express the appropriate receptor in target organs. Endocrine cells are typically composed of islands exocrine gland of secretory cells of epithelial origin that discharge their products into capillaries, unlike the cells of exocrine glands that release their products into an epithelial duct. Based on their chemical structure, hormones can be classified as: • proteins and glycoproteins • small peptides • amino-acid derivatives • steroids

Types of secretion Endocrine secretion: the cell content is released to the circulation on the basolateral membrane, through a basement membrane that separates the endocrine cells from the blood stream. Exocrine secretion: the cell is released from the apical membrane, directly to the body surface or cavity. It can be merocrine, apocrine or holocrine, depending on the

mechanism that mediates the secretion. Types of secretion

2. Define the components of the endocrine system • Major endocrine organs: the sole or major function of the organ is the synthesis, storage and secretion of hormones Histology of the Pituitary Gland and Endocrine System Notes 3

• Endocrine components within other solid organs: clusters of endocrine cells within other tissues • Diffuse endocrine system: scattered individual cells (or small clumps), usually within an extensive epithelium

Hypothalamus The is a small region located in the lower central part of the brain. It contains the cell bodies of neurosecretory neurons, which produce the hormones that in turn control hormonal secretion by the pituitary gland: • growth hormone-releasing hormone • thyrotropin-releasing hormone • corticotropin-releasing hormone • gonadotropin-releasing hormone • prolactin inhibitory factor (dopamine). In addition, the supraoptic and paraventricular nuclei of the hypothalamus produce the hormones (or antidiuretic hormone), which targets the kidney and , which targets the mammary gland and the uterus.

Hypothalamus-hypophyseal system Histology of the Pituitary Gland and Endocrine System Notes 4

Hypothalamic hormones Hormone Target Functions Growth hormone- Stimulates synthesis and Somatotropic cells releasing hormone release of GH Tyrotropin-releasing Thyrotropic and Stimulates synthesis and hormone mammotropic cells release of TSH and prolactin Stimulates synthesis of Corticotropin-releasing Corticotropic cells POMC and release of β-LPH hormone and ACTH Gonadotropin-releasing Stimulates the release of Gonadotropic cells hormone FSH and LH Prolactin inhibitory factor Mammotropic cells Inhibits release of prolactin (dopamine) Somatotropic and Inhibits the release of GH and Somatostatin thyrotropic cells TSH Vassopresin (anti-diuretic Collecting ducts in the Stimulates water re- hormone) kidney absorption Myoepithelial cells Stimulates contraction of the Oxytocin (mammary glands) and target cells smooth muscle (uterus)

3. Compare and contrast the cellular composition of the adenohypophysis (anterior pituitary) and neurohypophysis (posterior pituitary gland) a. Pituitary gland (hypophysis) The pituitary gland is located below the brain in a cavity of the sphenoid bone, the sella turcica. The pituitary consists of two glands, the anterior adenohypophysis, develops in the embryo from the oral ectoderm, and the posterior neurohypophysis, developed from the brain. The two glands that form the pituitary are united anatomically but have different functions. • Adenohypophysis Formed by 3 structures; the pars distalis or anterior lobe, the and the .

o Pars distalis: its main components are cords of epithelial cells interspersed with fenestrated capillaries. Fibroblasts produce reticular fibers supporting the cords of hormone-secreting cells. Hormones produced in the pars distalis regulate the function of other endocrine glands, milk secretion, melanocyte activity and the metabolism of muscle, bone and adipose tissue. Based on staining affinity, cells can be classified in chromophils, containing Histology of the Pituitary Gland and Endocrine System Notes 5

cytoplasmic granules that can be basophilic or acidophilic, and chromophobes. Basophilic chromophils are: . Gonadrotropic: produce follicle-stimulating and luteinizing hormones . Corticotropic: produce corticotrophin and melanocyte stimulating hormone . Thyrotropic: produce thyrotropin Acidophilic chromophils are: . Somatotropic: produce growth hormone . Mammotropic: produce prolactin Chromophobes are: . stem and undifferentiated progenitor cells . degranulated chromophilic cells As cells that produce different hormones may stain similarly, specific cell types cannot be identified by light microscopy staining, only by TEM or immunohistochemistry.

o Pars tuberalis: funnel-shaped region surrounding the infundibulum of the neurohypophysis. Most of the cells are basophilic gonadrotropic cells.

o Pars intermedia: thin zone of basophilic cells between the pars distalis and pars nervosa of the neurohypophysis. It develops from the dorsal wall of the hypophysis and contains colloid-filled cysts that represent remnants of that structure’s lumen. • Neurohypophysis It derives from a downgrowth of the nervous tissue from the hypothalamus. Contains nerve axons and glial cells (called ); it is comprised of two parts: o Pars nervosa: expanded distal portion containing the neurosececretory axons of the hypothalamo-hypophyseal tract. The cell bodies of these fibers lie in the supraoptic and paraventricular nuclei of the hypothalamus. The nerve terminals of these neurons are atypical in that they are non-synaptic and secrete hormones rather than neurotransmitters. The hormones are stored in granules at the nerve terminal and are visible in the light microscope as (also called neurosecretory bodies). The pars nervosa also contains fibroblasts, mast cells and pituicytes. o Infundibular stack: It also contains neurosecretory nerve endings from hypothalamic neurons (other than supraoptic and paraventricular nuclei). The hormones secreted in these regions enter the hypothalamo- Histology of the Pituitary Gland and Endocrine System Notes 6

hypophyseal portal system and regulate the endocrine cells of the adenohypophysis. 4. Describe the hypophyseal portal system and its physiological significance

The pituitary portal system, a special network of blood vessels, carries hormones from the hypothalamus to the anterior pituitary. The blood supply of the pituitary arises from paired arteries originating from the internal carotid arteries. The superior hypophyseal arteries supply the and the infundibular stack. These arteries form a primary capillary network or plexus that irrigates the stalk and median eminence. The capillaries rejoin to form the long portal veins that run to the pars distalis. The veins branch again to form the secondary capillary plexus in the adenohypophysis. The inferior hypophyseal artery forms capillaries that provide blood primary to the neurohypophysis. There are also short Pituitary portal system portal veins that link the pars nervosa with the pars distalis, of unknown function.

5. Compare and contrast the cellular composition of the adrenal cortex and adrenal medulla Adrenal glands are paired organs that lie near the superior poles of the kidneys. Each gland is covered by a dense connective tissue capsule that sends septa into the interior of the gland as trabeculae. The gland consists of two layers, the cortex and the medulla, with different origin, functions and morphology. • Adrenal cortex: it derives from mesoderm and contains cells that produce steroid hormones. The adrenal cortex has 3 concentric zones, each one producing a different class of hormones.

o : the external part, formed by closely packed, rounded or arched cords of columnar or pyramidal cells surrounded by capillaries. The cells in this region produce mineralocorticoids (aldosterone). o : consists of long cords of large polyhedral cells, separated by fenestrated sinusoidal capillaries. The cells in this region secrete glucocorticoids (cortisol) and small amounts of androgens. Histology of the Pituitary Gland and Endocrine System Notes 7

o : the innermost part of the cortex, in contact with the adrenal medulla. The cells in this region produce mainly dehydroepiandrosterone, a weak androgen that can be converted into testosterone in several tissues.

Adrenal gland

• Adrenal medulla: it derives from the neural crest. It is composed of chromaffin cells that can be considered modified postganglionic neurons. Chromaffin cells contain electron-dense granules filled with either epinephrine or norepinephrine. Epinephrine-producing cells locate near cortical sinusoids, whereas norepinephrine-producing cells locate near medullary arterioles. 6. Describe the organization and cellular features of the thyroid gland and parathyroid glands and the hormones their cells produce

a. Thyroid gland The thyroid gland is located in the cervical region anterior to the larynx. It originates from the foregut endoderm near the base of the future tongue. The parenchyma is formed by rounded epithelial structures called thyroid follicles. Each follicle consists of a simple epithelium surrounding a central lumen filled with colloid, which contains tyroglobulin, the precursor for the active thyroid hormones, thyroxine (or tetra- iodotyronine, T4) and tri-iodotyronine, T3. Parafollicular cells (C cells), which

produce calcitonin, can be found between follicles. Synthesis of thyroid hormones Histology of the Pituitary Gland and Endocrine System Notes 8

The production, storage and release of thyroid hormones involve a multistage process with both exocrine and endocrine: 1. Thyroglobulin (hormonally inactive) is synthesized in the RER and glycosylated in the RER and Golgi 2. Circulating iodine is incorporated through the basolateral cell membrane of the follicular cells 3. Iodine is transferred to the follicular lumen where it undergoes oxidation to active iodine 4. Tyrosine residues of tyroglobulin are iodinated in the lumen 5. Follicular cells take up colloid by endocytosis or pinocytosis. The endocytic vesicles fuse with lysosomes and move to the basolateral cell membrane while the thyroglobulin is degraded to render T3 and T4, which are then release to the circulation.

b. The parathyroids are four small glands located on the back of the thyroid gland. They derive from the pharyngeal pouches in the embryo. Each parathyroid gland is contained within a capsule that sends septa into the gland. The glands are composed of two types of cells, the chief cells that contain granules with parathyroid hormone; and the oxyphil cells, larger than chief cells, with acidophilic cytoplasm and abnormally shaped mitochondria. Parathyroid hormone (PTH) is produced by the chief cells. Lowered extracellular Ca2+ removes the calcium sensing receptor-dependent repression of PTH production. PTH is then free to mobilize Ca2+ from stores in bone. PTH production may also be regulated by phosphate.

7. Explain the structural features and functions of the pineal gland

The pineal gland is a small, pine cone-shaped organ in the brain. It develops with the brain from neuroectoderm in the roof of the diencephalon. It is covered by connective tissue. The most abundant secretory cells are the , which produce melatonin. It also contains interstitial glial cells, similar to astrocytes.

8. Bone as an endocrine organ In addition to its function providing protection and support to the soft organs and as a source of calcium, bone cells can produce molecules that are released to the circulation and affect other cells and tissues. Examples of hormone-like molecules produced by bone cells are fibroblast growth factor-23 (FGF-23) and osteocalcin. Histology of the Pituitary Gland and Endocrine System Notes 9

FGF-23 is produced by osteocytes and regulates phosphate reabsorption in the kidney. Osteocalcin is produced by osteoblasts and osteocytes and has been propose to affect the function of the adipose tissue, pancreatic β cells, muscle cells, and the male .

9. Define the diffuse neuro-endocrine system In addition to endocrine glands, many organs contain endocrine cells that produce hormones and have important endocrine functions. These organs include the heart, kidney, thymus, gut and gonads.