Lesson 1 Chapter 5 – The Central Endocrine Glands

Lesson 1 Chapter 5 – The Central Endocrine Glands 1 Unit 1 Study Guide Please refer back to Physiology 150 Study Guide (Unit 10.1) The body has two basic systems for communicating information to its tissues: the nervous system, which is used for short, rapid communications; and the endocrine system, which relies on slower, longer-lasting messengers (hormones) that are transported by the circulatory system. The two systems are not independent: hormones can influence the nervous system, and vice versa. Newly-formed hormones are instantly released or stored for future use. A stored hormone is attached to a dedicated protein in cytoplasmic secretory vesicles in the synthesizing cell. Some exceptions include thyroxine, which is attached to thyroglobulin, and is stored outside the follicle cells that produce it; and the steroid hormones, which are synthesized on-demand, and are not stored (unlike proteinaceous hormones). The effects of thyroxine or steroid hormones occur more slowly, but are longer-lasting. A hormone released from its endocrine cell is carried by the blood to its target. Different types of hormones are handled differently: large peptide hormones that are somewhat plasma soluble cannot be excreted in the urine; carrier proteins make steroid proteins and throxine more soluble and less likely to be eliminated in the urine. Many hormone carriers are specific, but blood albumin is a general carrier that delivers many hormones to their destinations. Lesson 1 Chapter 5 – The Central Endocrine Glands 2 Endocrine Glands divided into: central glands – – – – Hypothalamus Anterior pituitary (adenohypophysis) Posterior pituitary (neurohypophysis) Pineal gland peripheral glands – – – – – – – Thyroid gland Pancreas Parathyroid gland Ovaries Thymus gland Testes Adrenal gland Modes of Cell Signaling Endocrine signaling can be contrasted with other modes of signaling: neural signaling, paracrine signaling, and auto signaling. A key difference is the distance that the regulatory molecule travels to reach its target. Neurons are connected to their target cells via synapses. A neurotransmitter crossing a synaptic cleft will travel between 10 and 20 nanometers. A paracrine will travel only a few millimeters before it is broken down, so it can only act on nearby cells. By contrast, hormones travel via the circulation to reach their targets, which may be multiple tissues that are distant from each other and the endocrine cells. Thus, hormones could be said to have systemic effects. • • • • Endocrine: – secretion of hormones into the bloodstream by endocrine glands affecting distant targets Paracrine: – hormone molecule secreted by one cell affects adjacent cells Autocrine: – hormone molecule secreted by a cell affects the secreting cell Neurocrine: Lesson 1 Chapter 5 – The Central Endocrine Glands 3 – secretion of hormones into the bloodstream by neurons Hypothalamic-Pituitary Axis The hypothalamus in vertebrates integrates the endocrine and nervous systems. The hypothalamus is an endocrine organ located in the diencephalon of the brain. It receives input from the body and other brain areas, initiating endocrine responses to environmental changes. The hypothalamus acts as an endocrine organ as it synthesizes hormones and transports them along axons to the posterior pituitary gland. The hypothalamus also synthesizes and secretes regulatory hormones that control the endocrine cells in the anterior pituitary gland. In addition, it contains autonomic centers that control endocrine cells in the adrenal medulla via neuronal control. The pituitary gland, sometimes called the hypophysis or “master gland,” is located at the base of the brain in the sella turcica, a groove of the sphenoid bone of the skull. It is attached to the hypothalamus via a stalk called the pituitary stalk (or infundibulum). The pituitary has two distinct regions: the anterior pituitary and the posterior pituitary. These regions secrete nine different peptide or protein hormones. The anterior portion of the pituitary gland is regulated by releasing or release-inhibiting hormones produced by the hypothalamus. The posterior pituitary receives signals via neurosecretory cells to release hormones produced by the hypothalamus. Hypothalamic-pituitary control of hormone levels The dashed line represents feedback control. Lesson 1 Chapter 5 – The Central Endocrine Glands 4 Hormone Synthesis, Secretion and Metabolism Water-soluble hormones – Peptide hormones: contained within lipid bilayer of the vesicles and stored until a trigger results in exocytosis of the hormone into the extracellular space – Catecholamines: formed by enzymes within the cytoplasm that begin with tyrosine and through a series of steps convert it to dopamine, norepinephrine, or epinephrine Lipid-soluble hormones – Steroid hormones: formed on demand from cholesterol that is stored in the cell or retrieved from the circulating lipoproteins – Thyroid hormones: synthesis precedes secretion by weeks or months in the thyroid follicle and bound to protein thyroglobulin; secretion occurs via cleavage of the thyroid hormone based on systemic needs determined by the hypothalamus and pituitary gland Lesson 1 Chapter 5 – The Central Endocrine Glands 5 Second Messenger System Second messengers are molecules that relay signals received at receptors on the cell surface — such as the arrival of protein hormones, growth factors, etc. — to target molecules in the cytosol and/or nucleus. But in addition to their job as relay molecules, second messengers serve to greatly amplify the strength of the signal. Binding of a ligand to a single receptor at the cell surface may end up causing massive changes in the biochemical activities within the cell. There are 3 major classes of second messengers: 1. cyclic nucleotides (e.g., cAMP and cGMP) 2. inositol trisphosphate (IP3) and diacylglycerol (DAG) 3. calcium ions (Ca2+) 1. Cyclic adenosine monophosphate (cAMP) is a nucleotide generated from ATP through the action of the enzyme adenylate cyclase. The intracellular concentration of cAMP is increased or decreased by a variety of hormones and such fluctuations affect a variety of cellular processes. One prominent and important effect of elevated concentrations of cAMP is activation of a cAMP-dependent protein kinase called protein kinase A. Protein kinase A is nominally in an catalytically-inactive state, but becomes active when it binds cAMP. Upon activation, protein kinase A phosphorylates a number of other proteins, many of which are themselves enzymes that are either activated or suppressed by being phosphorylated. Such changes in enzymatic activity within the cell clearly alter its state. Now, let's put this information together to understand the mechanism of action of a hormone like glucagon:       Glucagon binds its receptor in the plasma membrane of target cells (e.g. hepatocytes). Bound receptor interacts with and, through a set of G proteins, turns on adenylate cyclase, which is also an integral membrane protein. Activated adenylate cyclase begins to convert ATP to cyclic AMP, resulting in an elevated intracellular concentration of cAMP. High levels of cAMP in the cytosol make it probable that protein kinase A will be bound by cAMP and therefore catalytically active. Active protein kinase A "runs around the cell" adding phosphates to other enzymes, thereby changing their conformation and modulating their catalytic activity - - abracadabra, the cell has been changed! Levels of cAMP decrease due to destruction by cAMP-phosphodiesterase and the inactivation of adenylate cyclase. Lesson 1 Chapter 5 – The Central Endocrine Glands 6 2. Inositol-1,4,5-trisphosphate (IP3) diffuses to the endoplasmic reticulum, where it triggers release of Ca2+ ions into the cytosol. Subsequently, the released Ca2+ and DAG activate protein kinase C (PKC). Lesson 1 Chapter 5 – The Central Endocrine Glands 3. Ca2+ release into the cytosol is amplituded and frequency modulated, and is regulated by: a) voltage-gated channels – after depolarization by an action potential Ca2+ ions are released from storage in the endoplasmic reticulum of smooth-muscle cells, the sarcoplasmic reticulum of striated (voluntary) muscles, taste-receptors for salt, neurons (trigger of nt release) b) receptor-operated ion channels in post-synaptic membranes, which open upon ntbinding c) Guanine nucleotide-binding protein-coupled receptors, also termed serpentine receptors (GPCRs), which trigger the release of calcium ions from the endoplasmic reticulum. 7 Lesson 1 Chapter 5 – The Central Endocrine Glands 8 Ca2+ is returned to the extracellular fluid by active transport: a) ATP-driven Ca2+-ATPase pump b) Na2++/Ca2+antiport exchanger pump that harnesses the energy of 3 Na2++ ions flowing down their concentration gradient to pump one Ca2+ against its concentration gradient 1. Ca2+ is returned to the endoplasmic/sarcoplasmic reticulum by a Ca2+-ATPase Central Endocrine Glands: – – – – Hypothalamus Anterior pituitary (adenohypophysis) Posterior pituitary (neurohypophysis) Pineal gland Hypothalamus The hypothalamus is a part of the brain located superior and anterior to the brain stem and inferior to the thalamus. It serves many different functions in the nervous system, and is also responsible for the direct control of the endocrine system through the pituitary gland. The hypothalamus contains special cells called neurosecretory cells—neurons that secrete hormones:        Thyrotropin-releasing hormone (TRH) Growth hormone-releasing hormone (GHRH) Growth hormone-inhibiting hormone (GHIH) Gonadotropin-releasing hormone (GnRH) Corticotropin-releasing hormone (CRH) Oxytocin Antidiuretic hormone (ADH) All of the releasing and inhibiting hormones affect the function of the anterior pituitary gland. TRH stimulates the anterior pituitary gland to release thyroid-stimulating hormone. GHRH and GHIH work to regulate the release of growth hormone—GHRH stimulates growth hormone release, GHIH inhibits its release. GnRH stimulates the release of follicle stimulating hormone and luteinizing hormone while CRH stimulates the release of adrenocorticotropic hormone. The last two hormones—oxytocin and antidiuretic hormone—are produced by the hypothalamus and transported to the posterior pituitary, where they are stored and later released. Lesson 1 Chapter 5 – The Central Endocrine Glands 9 Pituitary Gland The pituitary gland, also known as the hypophysis, is a small pea-sized lump of tissue connected to the inferior portion of the hypothalamus of the brain. Many blood vessels surround the pituitary gland to carry the hormones it releases throughout the body. Situated in a small depression in the sphenoid bone called the sella turcica, the pituitary gland is actually made of 2 completely separate structures: the posterior and anterior pituitary glands. 1. Posterior Pituitary: [neurohypophysis] The posterior pituitary gland is actually not glandular tissue at all, but nervous tissue instead. The posterior pituitary is a small extension of the hypothalamus through which the axons of some of the neurosecretory cells of the hypothalamus extend. These neurosecretory cells create 2 hormones in the hypothalamus that are stored and released by the posterior pituitary:   Oxytocin triggers uterine contractions during childbirth and the release of milk during breastfeeding. Antidiuretic hormone (ADH) prevents water loss in the body by increasing the re-uptake of water in the kidneys and reducing blood flow to sweat glands. 1. Anterior Pituitary: [adenohypophysis] The anterior pituitary gland is the true glandular part of the pituitary gland. The function of the anterior pituitary gland is controlled by the releasing and inhibiting hormones of the hypothalamus. The anterior pituitary produces 6 important hormones:       Thyroid stimulating hormone (TSH), as its name suggests, is a tropic hormone responsible for the stimulation of the thyroid gland. Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex, the outer part of the adrenal gland, to produce its hormones. Follicle stimulating hormone (FSH) stimulates the follicle cells of the gonads to produce gametes—ova in females and sperm in males. Luteinizing hormone (LH) stimulates the gonads to produce the sex hormones— estrogens in females and testosterone in males. Human growth hormone (HGH) affects many target cells throughout the body by stimulating their growth, repair, and reproduction. Prolactin (PRL) has many effects on the body, chief of which is that it stimulates the mammary glands of the breast to produce milk. Lesson 1 Chapter 5 – The Central Endocrine Glands 10 Pineal Gland The pineal gland is a small pinecone-shaped mass of glandular tissue found just posterior to the thalamus of the brain. The pineal gland produces the hormone melatonin that helps to regulate the human sleep-wake cycle known as the circadian rhythm. The activity of the pineal gland is inhibited by stimulation from the photoreceptors of the retina. This light sensitivity causes melatonin to be produced only in low light or darkness. Increased melatonin production causes humans to feel drowsy at nighttime when the pineal gland is active.