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Unformatted text preview: ENDOCRINOLOGY COORDINATION OF PHYSIOLOGICAL PROCESSES: -In a living organism there must be coordination of number of physiological activities taking place simultaneously such as: movement, respiration, circulation, digestion, excretion and metabolism. -The central nervous system and the endocrine system represent the two major means by which these functions are coordinated. LONG DISTANCE COMMUNICATION: -Communication between cells that are not in contact is achieved through a number of chemical substances, which are secreted by releasing cells and interact with specific receptors on distant target cells. -Signaling through these receptors leads to a specific physiological effect. Always 1. ENDOCRINE SIGNALING: Involves hormone secretion into the blood by an endocrine gland. The hormone is transported by the blood to a distant target site. - Hormones do not only come from secreting endocrine glands - Cascades of hormone productions Primary endocrine organ Secondary endocrine organs Figure 1.1. NEUROENDOCRINE SIGNALING Source of the hormones: nerves -Hormones released by the hypothalamus travel through a portal towards the pituitary signaling the release of other hormones - Long distance communication between the brain and peripheral tissues Figure 1.2. Paracrine Signaling Autocrine Signaling Cell talks to itself - a cell can produce a hormone and express receptors for it as well Can be of the same or different cell type e.g. epithelial cells Figure 1.3 Figure 1.4 Communication by hormones (or neurohormones) usually involves six steps. Can True for 100% of hormonal communi cation (1) Synthesis of the hormone by endocrine cells (or neurons in case of neurohormone). Hormones can also be ingested: fatty acids, vitamin B, D (2) Release of the hormone by the endocrine cells (or the neurohormones by the neurons) True for the classical theory (3) Transport of the hormone or neurohormone to the target site by the blood stream. (4) Detection of the hormone or neurohormone by a specific receptor protein on the target cells. (5) A change in cellular metabolism triggered by the hormonereceptor interactions (6) Removal of the hormone, which often terminates the cellular response A signal sent by a hormone induces its own removal classical negative feedback loop Anatomically and physiologically different - Goiters - Produce thyroid hormone “Classical” Endocrine Organs - Natrium - Sodium - Atrial peptide that stimulates the loss of Na in urine - Important for maintaining blood pressure Called parathyroid because it is in the same place as the thyroid - different hormonal, anatomical and physiological function Figure 1.5. Hypothalamic-Pituitary Signaling. HypothalamicHypophyseal portal system -via blood vessels of the pituitary stalk. -Hypothalamic-Hypophyseal Portal System - from the hypothalamus to the the adenohypophysis (anterior pituitary). The anterior and posterior pituitary are anatomically distinct -hypothalamic neurohormones either activate or inhibit activity of one of the six types of hormone-producing cells in the anterior pituitary. Induce -called either releasing hormones (releasing factors) or inhibiting hormones (inhibiting factors). production and/or release of a pituitary hormone Figure 1.6 TABLE 2: CLASSES OF HORMONES BASED ON THEIR STRUCTURE PEPTIDES AND PROTEINS GLYCOPROTEINS POLYPEPTIDES - Follicle Stimulating Hormone (FSH) -Luteinizing Hormone (LH) - Thyroid Stimulating Hormone (TSH) - Human Chorionic Gonadotropin (HCG) - Hormones that have been structurally modified with the addition of oligosaccharides - Can affect binding to a receptor, degradation by a protease Know these: STEROIDS AMINES - Adrenocorticotropin - Aldosterone -Epinephrine Hormone (ACTH) - Cortisol -Thyroxine (T4) - Growth Hormone (GH) - Estradiol -Triiodothyronine (T3) - Prolactin - Progesterone -Melatonin - B-Lipotropin (B-LPH) - Testosterone - B-Endorphin - Vitamin D - Insulin - Glucagon - Insulin-like growth factors (IGFs) or (Somatomedins) - Parathyroid Hormone (PTH) If a hormone is non- Calcitonin proteinaceous it does not have - Oxytocin a gene that encodes for it, but - Vasopressin can still have the enzymes - Angiotensin (ADH) required for its biochemical - Relaxin action - Somatostatin - Corticotropin Releasing Hormone (CRH) - Cholecystokinins - and others Can be extremely small, a handful of amino acids SYNTHESIS OF PROTEIN HORMONES - There is a difference between synthesis and synthesis and release - A gene that encodes for a hormone is longer than the final gene product (hormone) - A hormone will undergo a maturation process where its N and C terminals are cleaved off - A hormone is the proteolytic cleavage product of the gene product oligosaccharide modifications in golgi Figure 1.7 Structures of some steroid hormones - The addition of a methyl group on the A group of testosterone makes the A group puckered - The removal of this methyl group would result in an estrogen hormone A Weak androgen Figure 1.8 Flat benzene group STRUCTURES OF Derived from iodine and tyrosine THYROID HORMONES is located on an extremely large that protein Reverse T3 - not a physiological hormone, I is on the other side of the molecule Figure 1.9 “lock and key” mechanism for a hypothetical membrane receptor Similar to enzymatic theory 2 Important events to hormone binding: - Interaction of the hormone to the receptor - The response of the receptor - a change in conformation, allowing interaction with proteins downstream in the cascade of reactions Figure 1.10 Properties of Hormone Receptors. (a) SPECIFICITY: recognition of single hormone or hormone family. Exception - many structurally different hormones are able to bind to receptors in the liver and all result in the same regulation of metabolism (b) AFFINITY: High affinity for the hormone; i.e. binding hormone at can its physiological concentration. Glucose in thebind hormonally, binding curve is millimolar range (c) SATURABILITY: Should show saturability; i.e. a finite number of receptors. (d) MEASUREABLE BIOLOGICAL EFFECT: A measurable biological response due to interaction of hormone with its receptor. Receptor Regulation. Receptors can be upregulated either by increasing their activity in response to hormone or their synthesis. Or increasing their concentration Receptors can be downregulated either by decreasing their activity or their synthesis mechanisms by which a hormone can exert effects on target cells: 1) Direct effects on function at the cell membrane. G protein cascade, cAMP protein synthesis 2) Intracellular effects mediated by second messenger systems. 3) Intracellular effects mediated by genomic or nuclear action. (1) Direct effect. Regulation of glucose transport by insulin Figure 1.11 (2) Signaling via an intracellular second messenger. Seven transmembrane receptor Production of cAMP, a secondary messenger which stimulates the activation of protein kinase Figure 1.12 (3) Intracellular genomic signaling. - Cholesterol is a major membrane constituent - Steroid membranes are able to cross a cell membrane on their own - Ultimately change levels of transcription - Vitamin D receptors are located in the nucleus Figure 1.13 ...
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