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Endocrine System Human Physiology Unit 3 Endocrine System • Various glands located throughout the body • Some organs may also have endocrine functions • Endocrine glands/organs synthesize and release hormones • Hormones travel in plasma to target cells Functions of the Endocrine System • Differentiation of nervous and reproductive system during fetal development • Regulation of growth and development • Regulation of the reproductive system • Maintains homeostasis • Responds to changes from resting state Mechanisms of Hormone Regulation • Hormones have different rates and rhythms of secretion • Hormones are regulated by feedback systems to maintain homeostasis • Receptors for hormones are only on specific effector cells • Excretion of hormones vary for steroid hormones and peptide hormones Regulation of Hormone Secretion • Release of hormones occurs in response to • A change from resting conditions • Maintaining a regulated level of hormones or substances • Hormone release is regulated by • Chemical factors (glucose, calcium) • Endocrine factors (tropic hormones, HPA) HPA = Hypothalamic-Pituitary Axis • Neural controls (sympathetic activation) Hormone Feedback Systems Negative feedback maintains hormone concentrations within physiological ranges • Negative feedback • Feedback to one level Loss of • Long-loop Negative Feedback feedback • Feedback to two levels control often leads to • Hypothalamus-Pituitary-Gland Axis pathology Negative Feedback Short-Loop Negative Feedback Long-Loop Negative Feedback Hormone Transport Peptide/Protein Hormones Lipid Soluble Hormones • Circulate in free forms • Circulate bound to carrier or (unbound) transport proteins (albumins) • • Short half life Remain in blood from hours to days • Degraded by circulating enzymes • Examples • Androgens • Examples • Estrogen, progesterone • Glucocorticoids • Insulin: t ½ = 3-5 minutes • Hypolthalamic hormones • Mineralcorticoids • Vitamin D • Pituitary hormones • Thyroid hormone • Parathyroid Hormone (PTH) • Arachidonic acid derivatives Hormone Receptors • A hormone released in to plasma circulates throughout the entire body • Only cells with the receptors for those hormones can respond • Cell receptors have 2 functions • Recognize and bind to hormone with high affinity • Initiate a signal to intracellular effectors Hormone Receptors • Sensitivity is related to the number of receptors • Plasma membrane receptors are constantly being synthesized and degraded • Regulation as a response • Changes in [receptor] may occur within hours • Physiological conditions affect receptor number and affinity • pH • Temperature • Ion concentration • Diet • Other chemicals (drugs) Plasma Membrane Receptors Signal Transduction 2nd Messenger Associated Hormones 2nd Messenger Associated Hormones cAMP Adrenocorticotropic Hormone (ACTH) Calcium Angiotensin II Luteinizing Hormone (LH) Gonadotropin-Releasing Hormone (GnRH) Human Chorionic Gonadotropin (hCG) Antidiuretic Hormone (ADH) Follicle-stimulating Hormone (FSH) Thyroid Stimulating Hormone (TSH) IP3 and DAG Angiotensin II Antidiuretic Hormone (ADH) Antidiuretic Hormone (ADH) Thyrotropin Releasing Hormone (TRH) Parathyroid Hormone (PTH) Glucagon Tyrosine Kinase Insulin JAK Growth Hormone (GH) Leptin cGMP Atrial Natriuretic Peptide (ANP) Prolactin Hormone Effects • Binding of hormones t their receptors trigger 3 types of responses 1. Acts on pre-existing channel-forming proteins to change membrane permeability 2. Activating pre-existing proteins by a 2nd messenger 3. Activating genes resulting in protein synthesis • Direct Effects • Changes in cell function result from hormone binding • Insulin causes cellular glucose/amino acid uptake • Permissive Effects • Hormone induced changes that facilitate the maximal response of a cell • Insulin has a permissive effect on mammary gland cells, facilitating their response to prolactin Hormone Excretion • Steroid Hormone Excretion • Excreted directly by the kidneys • Metabolized (conjugated) by the liver which inactivates them and makes them more water soluble • Peptide Hormone Excretion • Deactivated by enzymes and excreted in urine or feces Hypothalamic-Pituitary Axis Anterior Pituitary Posterior Pituitary • Neurosecretory cells in the • Hypothalamic neurons extend into hypothalamus communicate the posterior pituitary with endocrine cells in the • Hypothalamohypophysial nerve tract anterior pituitary • Neurons of the Supraoptic Nucleus • Hypothalamo-pituitary portal and Paraventricular Nucleus vessels • Hormones are stored and released • Endocrine cells of the anterior from the posterior pituitary into pituitary secrete their hormones general circulation into general circulation Hypothalamic-Pituitary Axis Hypothalamo-pituitary portal vessels Capillaries in Infundibulum ↓ Venule ↓ Capillaries in Anterior Lobe ↓ Hypothalamohypophysial Nerve Tract Venule ↓ General Circulation Hypothalamus Hypothalamus • Neural input to the neurosecretory cells of the hypothalamus control their actions • Neurons from other parts of the brain • Sensory feedback to the hypothalamus • Neurosecretory cells secrete releasing and inhibiting hormones • Hypophysiotropic Hormones • Tropic hormones cause other hormones to be produced • Tropic Hormones released by the hypothalamus that cause hormones to be released by the anterior pituitary Hypothalamus Hypothalamus Hormone Target Tissue Actions Thyrotropin-Releasing Hormone (TRH) Anterior Pituitary (+) Thyroid stimulating Hormone (TSH) Gonadotropin-Releasing Hormone (GnRH) Anterior Pituitary (+) Follicle Stimulating Hormone (FSH) (+) Luteinizing Hormone (LH) Growth Hormone Releasing Hormone (GHRH) Anterior Pituitary (+) Growth Hormone (GH) Somatocrinin Somatostatin Anterior Pituitary (-) Growth Hormone (GH) (-) Thyroid Stimulating Hormone (TSH) Corticotropin-Releasing Hormone (CRH) Anterior Pituitary (+) Adrenocorticotropic Hormone (ACTH) (+) β endorphin Substance P Anterior Pituitary (+) Growth Hormone (GH) (+) Follicle Stimulating Hormone (FSH) (+) Luteinizing Hormone (+) Prolactin (-) Adrenocorticotropic Hormone (ACTH) Prolactin-Releasing Factor (PRF) Anterior Pituitary (+) Prolactin Dopamine (DA) Anterior Pituitary (-) Prolactin Anterior Pituitary Anterior Pituitary • Also called adenohypophysis • Chromophils are the secretory cells of the anterior pituitary • 7 different sub-types • Secretes tropic hormones • Causes target glands to secrete hormones • Regulation of the anterior pituitary • Feedback of the releasing/inhibiting hormones • Feedback from target gland hormones • Direct effects of neurotransmitters Anterior Pituitary Anterior Pituitary Hormone Target Organ Actions Adrenocorticotropic Hormone (ACTH) Adrenal Cortex (+) Cortisol, DHEA Melanocyte Stimulating Hormone (MSH) Anterior Pituitary (+) Secretion of melatonin Growth Hormone (GH) Liver (and Muscle, Bone) (+) Insulin-Like Growth Factor (IGF-1) Prolactin Mammary Glands (+) production of milk Thyroid-Stimulating Hormone (TSH) Thyroid Gland (+) Thyroid Hormone (T3, T4) (+) iodide uptake Luteinizing Hormone (LH) Gonads (+) progesterone Women – granulosa cells Ovulation Men – Leydig cells (+) testosterone Testicular growth Follicle Stimulating Hormone (FSH) Gonads (+) estrogen Women – granulosa cells Follicle development Men – Sertoli cells Spermatogenesis β-Lipotropin Adipocytes Lipolysis β-Endorphins Adipocytes Analgesia, food and water intake, (Brain opioid receptors) body temperature regulation Posterior Pituitary Posterior Pituitary • Also called neurohypophysis • Secretes 2 peptide hormones • Oxytocin • Antidiuretic Hormone (ADH) • Secreted from the hypothalamus • Supraoptic nucleus • Paraventricular nucleus Posterior Pituitary Posterior Pituitary Hormone Target Gland Actions Oxytocin Uterine smooth muscle Causes uterine contraction Mammary Glands Causes the “milk ejection” reflex Antidiuretic Hormone (ADH) Kidney tubules Controls plasma osmolality Pineal Gland Pineal Gland • Contains photoreceptor cells that secrete Melatonin • Synthesized from tryptophan • tryptophan→serotonin→melatonin • Melatonin release: • Stimulated by exposure to dark • Inhibited by exposure to light • Melatonin regulates circadian rhythms and reproductive systems Thyroid Gland Thyroid Gland • Neurons of the ANS terminate on blood vessels of the thyroid • ACh • Catecholamines • Thyroid gland secretes 2 Actions of TSH on the Thyroid 1. Immediate release of stored thyroid hormones hormone • Thyroid hormone 2. Increased iodide uptake and oxidation 3. Increase in thyroid hormone synthesis • Calcitonin 4. Increase in the synthesis and secretion of prostaglandins by the thyroid 5. Stimulates the growth and maintenance of the thyroid Thyroid Gland Thyroid Gland Feedback • Regulation of thyroid hormone by long-loop negative feedback Thyroxine (T4) • Stimulus for secretion of TRH is monitored in from the hypothalamus plasma for • Sleep feedback • Extreme cold • Exercise • Stress • Low plasma glucose Thyroid Hormone Thyroid Gland Thyroid Hormone produced: Synthesis 90% T4 10% T3 • Follicular cells form thyroid follicles • Thyroid Hormone is synthesized inside the follicles • Triiodothyronine (T3) • Thyroxine (T4) • Iodide is attached to tyrosine rings bound to thyroglobulin inside the follicle • MIT+DIT = T3 • DIT+DIT = T4 MCT: Thyroid hormone transporter Thyroid Gland Thyroid Hormone TH Receptors • In the tissues, T4 is converted to T3 which binds to nuclear hormone receptors • Thyroid beta receptor (THβ1, THβ2) • Liver, brain • Modulates cholesterol and triglyceride levels • Thyroid alpha receptor (THα1) • Heart • Modulates heart
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  • The Regulation of Parathyroid Hormone Secretion and Synthesis

    The Regulation of Parathyroid Hormone Secretion and Synthesis

    BRIEF REVIEW www.jasn.org The Regulation of Parathyroid Hormone Secretion and Synthesis Rajiv Kumar* and James R. Thompson† *Division of Nephrology and Hypertension, Department of Internal Medicine, Biochemistry and Molecular Biology, and †Department of Physiology, Biophysics and Bioengineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota ABSTRACT Secondary hyperparathyroidism classically appears during the course of chronic renal basis of these observations regarding failure and sometimes after renal transplantation. Understanding the mechanisms by pathogenesis, therapy for 2°HPT in the which parathyroid hormone (PTH) synthesis and secretion are normally regulated is context of CKD and ESRD includes the important in devising methods to regulate overactivity and hyperplasia of the para- control of serum phosphate concentra- ϩ thyroid gland after the onset of renal insufficiency. Rapid regulation of PTH secretion tions, the administration of Ca2 and in response to variations in serum calcium is mediated by G-protein coupled, calcium- vitamin D analogs, and the administra- sensing receptors on parathyroid cells, whereas alterations in the stability of mRNA- tion of calcimimetics.33,34,16,35,36 encoding PTH by mRNA-binding proteins occur in response to prolonged changes in Nevertheless, 2°HPT remains a signifi- serum calcium. Independent of changes in intestinal calcium absorption and serum cant clinical problem and additional meth- calcium, 1␣,25-dihydroxyvitamin D also represses the transcription of PTH by associ- ods for the treatment of this condition would ating with the vitamin D receptor, which heterodimerizes with retinoic acid X receptors be helpful, especially in refractory situations, to bind vitamin D-response elements within the PTH gene.