ENDOCRINE PHYSIOLOGY
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Bicol University College of Medicine Doctor of Medicine - Masters in Public Administration Subject:
Integrated Basic Sciences
Lecturer: Facilitator:
Dr. Edberto General, MD Dr. Virgilio Ludovice, MD
Title: Endocrinology (Introduction & Pituitary Gland) nd TRANS HEAD: MARAVILLAS, Micah James S. Sem/ A.Y.: 2 /A.Y. 2014-2015 Transcribers: ABANO, P., BRON, J., GARAY, M., MARAVILLAS, J., OLIVERA, T., TABLIZO, K., ZEPEDA, K.
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OUTLINE ENDOCRINOLOGY Principal Endocrine Organs And Tissues Of The Body Three General Classes Of Hormones Transport and Clearance of Hormones in the Blood The Pituitary Gland Formation of the Pituitary Gland Anterior and Posterior Pituitary Gland Hypothalamic-Hypophyseal Portal Blood Vessels in the Anterior Pituitary Gland Major Cell Types Types of the Anterior Pituitary Gland and Their Major Functions Hormones of the Anterior Pituitary Gland Hormones of the Posterior Pituitary Gland Growth Hormones and Their Metabolic Effects Growth Hormones – Stimulation of Cartilage and Bone Growth Regulation of growth Hormone Secretion Abnormalities of Growth Hormone Secretion ADH and its Physiological Functions Regulation of ADH Production OBJECTIVES To be able to discuss and know the principal endocrine endocrine organs and its functions To be able to describe the pituitary gland and discuss discuss the hormones secreted Discuss the growth hormone and its metabolic effects Discuss the importance of ADH and its functions Know the differential growth hormone abnormalities
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These hormones are released in to the circulating blood and affect or influence the function of cells at another location in the body The endocrine system is essential for cell-to-cell communication and also for maintenance of the following functions: Food seeking and satiety Metabolism and caloric economy Growth and differentiation Reproduction Homeostasis Response to environmental change Arousal, defense, flight, and secluding behaviors.
COMPONENT ORGANS OF THE ENDOCRINE SYSTEM a. b. c. d. e. f. g. h. i. j. k.
Pituitary Gland Adrenals Thyroid Gland Parathyroid Gland Pineal Gland Thymus Pancreas Kidneys Testis Ovaries Placenta
ENDOCRINOLOGY (INTRODUCTION AND PITUITARY GLAND ) ENDOCRINOLOGY DEFINITION Study of processes involved in the regulation and integration of cells and organ systems by hormones •
HORMONE Chemical substance secreted by one group of cells with effects or control on other cells Exert their effects by binding to specific receptors in the cells of the target organ. •
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ENDOCRINE GLAND Ductless •
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Highly vascularized for efficient and fast distribution of hormones into the blood stream and their target organs Generally contain epithelial cells arranged in chords Secretion is INWARD It is a tissue that produces chemical substances called hormones FIGURE 1:Human Body Showing Some of the Important Component Organs of the Endocrine System
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ENDOCRINE SYSTEM #
CLASSES OF HORMONES 1) 2) 3)
PEPTIDES STEROIDS AMINO ACID DERIVATIVES Function like steroids o Function like peptides o PEPTIDE HORMONES Water soluble HYDROPHILIC in nature ! ! When secreted in plasma, it blends well with water containing blood No specific transport mechanism ! THEY ARE NOT BOUND TO PLASMA PROTEINS WHILE THEY ARE BEING TRANSPORTED IN THE BLOODSTREAM!!! Major predominant form is in the FREE FORM. ! Very few are bound to a carrier protein eg. GH and ! IGF-1 Act by binding to receptors on the CELL MEMBRANE SURFACE (integral protein) because of the hydrophilic nature Synthesized as larger precursors in the RER first and then stored in secretory vesicles within endocrine cells.
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NEED SECOND MESSENGERS (amplifies transmitted signals) to exert their action. SECRETORY PEPTIDES Exemplefied by: PITUITARY HORMONES " Pituitary Gland HYPOTHALAMIC HORMONES " Hypothalamus INSULIN AND GLUCAGON " Endocrine Pancreas PTH " Parathyroid Hormones Onset of effect is FAST but easily degraded by PEPTIDASES therefore the duration of action is SHORT.
STEROID HORMONES LIPOPHILIC Easily diffuse across cell membrane o Exert their effects by binding to receptors found at o the CYTOPLASM or NUCLEUS Needs carrier protein o Precursor CHOLESTEROL – most steroid hormones o 7-dehydrocholesterol – vitamin D metabolites o BOUND TO PLASMA PROTEINS Eg. Testosterone and Estrogen o Bound to SHBG or Sex Hormone Binding # Globulin MAJOR PREDOMINANT FORM = PROTEIN o BOUND Synthesized in SER •
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NO STORAGE FORM for any steroid hormone Meaning they have to be synthesized first o whenever needed. Affects gene expression; increase of decrease synthesis of key regulatory proteins of the cell. Hence, onset of action for the majority is relatively slower than peptides. Duration of effects is longer. GONADS - Androgen, Estrogen, Progestin ADRENAL CORTEX – Glucocorticoids, Mineralocoticoids
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THYROID HORMONES in the thyroid gand o Lipid soluble and interact with intracellular nuclear receptors Function like PEPTIDES Dopamine, Epinephrine, and Norepinephrine o Secreted by adrenal medulla and nerves # Interact with cell membrane surface # receptors ALL AMINO ACID DERIVATIVES ARE SYNTHESIZED IN THE CYTOPLASM ALL AMINO ACID DERIVATIVES HAVE A STORAGE FORM (THYROID FOLLICLES)
TWO TYPES OF HORMONES IN THE PLASMA FREE FORM Biologically active •
For a hormone to interact with the receptor, it has to be in this form! BOUND FORM Bound to a cerrier or transport protein Will only interact with the receptor once it is liberated from the transport protein Binding to a carrier protein extends half life of the hormone. If it is secreted, bound form will not be degraded since it is still bound to a carrier or trnasport protein. Since steroids are greatly bound in the plasma, they have LONGER HALF LIVES because they serve as reservoir in the plasma •
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RECAP!!! (Added notes form Dr. General’s Lecture) AMINO ACID DERIVATIVES Dopamine Catecholamine Thyroid Hormone SMALL NEUROPEPTIDES GnRH TRH Somatostatin Vasopressin (ADH) LARGE PROTEINS Insulin LH PTH -produced by classic endocrine glands STEROID Cortisol Estrogen -cholesterol based precursors VITAMIN DERIVATIVES Retinoids (vit.A) Vitamin D
AMINO ACID DERIVATIVES • •
Derived form TYROSINE or TRYPTOPHAN Function like STEROIDS
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ENDOCRINE SYSTEM PITUITARY GLAND / HYPOPHYSIS
DIVISIONS OF THE PITUITARY GLAND
ANTERIOR PITUITARY GLAND or ADENOHYPOPHYSIS Has the characteristics of an ENDOCRINE GLAND •
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PARS DISTALIS " largest, anterior portion PARS TUBERALIS " hugs/enclose the stalk PARS INTERMEDIA " in between adenohypophysis and neurohypophysis
POSTERIOR PITUITARY GLAND or NEUROHYPOPHYSIS Has the characteristics of a BRAIN TISSUE INFUNDIBULUM " bridges hypothalamic and hypopheseal systems •
FIGURE 2: Pituitary Gland. Coronal Section of the Brain.
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GROSS ANATOMY Lies in a cavity of the sphenoid bone known as the SELLA TURCICA and ventral to the diaphragm sella. INFUNDIBULUM – connects the Pituitary Gland to the Hypothalamus (responsible for NEUROENDOCRINE CONTROL " inhibitory or stimulatory) Regulated by the endocrine functions of the hypothalamus 0.5g in males and 1.5g in multiparous females 600mg on average o Diameter: 10x13x16m
PARS NERVOSA " majority of the posterior pituitary gland and is the storage site of OXYTOCIN and VASOPRESSIN (ADH)
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Divided in ANTERIOR and POSTERIOR LOBES Anatomical Relations: OPTIC CHIASM " first affected in enlarged o Pituitary Internal Carotid Artery o CN III (Oculomotor) o CN IV (Trochlear) o BLOOD SUPPLY: Superior and Inferior Hypophyseal arteries HYPOTHALAMIC o Comes from the PITUITARY PORTAL # PLEXUS major blood source for the ANTERIOR PITUITARY GLAND INFERIOR HYPOPHYSEAL ARTERIES # " major blood source for the posterior pituitary gland
FIGURE 3: Divisions of the Pituitary Gland
NEUROVASCULAR SYSTEMS 1)
Hypothalamo-Hypophyseal Portal System (VASCULAR) ONLY IN ANTERIOR PITUITARY GLAND •
From the hypothalamus to the anterior pituitary gland Carries neuropeptides form the median eminence to the adenohypophysis where they either stimulate or inhibit hormone release of the anterior pituitary endocrine cells. Hypothalamic/Hypophyseal Tract (AXONS) Transverses the neurohypophysis •
EMBRYOLOGY OF THE PITUITARY GLAND
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ADENOHYPOPHYSIS / ANTERIOR PITUITARY GLAND Initially arise from the ORAL ECTODERM •
Rathke’s Pouch / Hypophyseal Pouch Cranially outpouching from the oral ectoderm that o develops during the second month. Cells of the ANTERIOR wall of this pouch will o proliferate and form the PARS ANTERIOR. ORAL ECTODERM AND RATHKE’S POUCH can o both be the embryonic origin of the Anterior Pituitary Gland NEUROHYPOPHYSIS / POSTERIOR PITUITARY GLAND Arises form the floor of the DIENCEPHALON INFUNDIBULUM " grows caudally or inferiorly from the floor of the diencephalon to differentiate into STALK/PARS NERVOSA of the pituitary gland. •
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BLOOD SUPPLY •
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Its axons branch form the PARAVENTRICULAR and SUPRAOPTIC nuclei which secrete oxytocin and ADH.
INTERNAL CAROTID ARTERY Superior Hypophyseal Artery o Pars tuberalis # Infundibular Stalk # Median Eminence # Inferior Hypophyseal Artery o Posterior Pituitary Gland # # Stalk Drained by the HYPOPHYSEAL VEIN
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ENDOCRINE SYSTEM !
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Regulates the production of adrenocortical hormones THYROTROPIN / THYROID STIMULATING HORMONE (TSH) ! Modulates thyroid hormone production in the thyroid gland PROLACTIN (PRL) ! Promotes development of the mammary glands for lactation FOLLICLE STIMULATING HORMONE (FSH) Promotes the development of oocyte/spermatocyte ! LUTEINIZING HORMONE (LH) ! Promotes estrogen/testosterone production HORMONES – POSTERIOR PITUITARY GLAND
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FIGURE 4: Hypothalamic-Hypophyseal Tract and Blood Supply CELLS OF ANTERIOR PITUITARY GLAND AND THEIR FUNCTIONS SOMATOTROPHS Hormone: SOMATOTROPIN (GH) Stimulates growth in epiphyseal plates of LONG BONES via (insulin-like growth factors) IGFs produced in the liver •
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VASOPRESSIN Antidiuretic hormone ! Regulates water reabsorption in the collecting ! tubules (and the distal parts of the DCT) of the kidneys Produce vasoconstriction = “vasopressin” ! OXYTOCIN Uterine smooth muscle contraction ! Milk letdown !
LACTOTROPHS MAMMOTROPHS Hormone: PROLACTIN •
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Promotes MILK SECRETION
GONADOTROPHS Hormone: FSH and LH; (Interstitial Cell Stimulating Hormone) ICSH in men •
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Ovarian follicle development secretion in women Spermatogenesis in men
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Ovarian follicle maturation and progesterone secretion in women Interstitial cell androgen secretion in mean
THYROTROPHS Hormone: THYROTROPIN (TSH) Stimulates Thyroid Hormone Synthesis, Liberation •
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Storage,
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CORTICOTROPHS Hormones: ADRENAL CORTICOTROPIN (ACTH) and LIPOTROPIN (LPH) ACTH – stimulates secretion of adrenocortical hormones LPH – helps regulate lipid metabolism
FIGURE 5: Hormones of Anterior and Posterior Pituitary Gland
HORMONES – ANTERIOR PITUITARY GLAND
GROWTH HORMONE
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GROWTH HORMONE (GH) Promotes somatic growth ! Protein formation, cell ! differentiation
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multiplication
ADRENOCORTICOTROPIC HORMONE (ACTH)
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Most abundant of the pituitary hormones SOMATOTROPHS – 50% of total Anterior Pituitary cell population SOMATOSTATIN synthesized in medial preoptic area of hypothalamus and inhibits GH secretion ESTROGEN induces GH
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ENDOCRINE SYSTEM
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Chronic glucocorticoid excess " suppress GH release LIVER and CARTILAGE " greatest number of GH receptors GH may decrease insulin sensitivity and this in turn leads to a compensatory mechanism " HYPERINSULINEMIA Short half-life – 20-15 minutes; when it reaches the liver it is cleaved by the hepatic enzymes
ANTIDIURETIC HORMONE •
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SECRETION •
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GHRH " stimulates GH synthesis and release from the arcuate nucleus of the hypothalamus GHRELIN directly stimulate GH release
IGF 1 / SOMATOMEDIN (Liver) peripheral target hormone for GH FEEDS BACK TO INHIBIT GH mediate effects of GH SRIF paraventricular nucleus of hypopthalamus; inhibits GH secretion ACTIONS OF GH LONGITUDINAL BONE GROWTH As long as epiphyseal plates are still open o JAK-STAT receptor on cell membrane surface o MUSCLE MASS BUILD UP Anabolic effect o
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Aka VASOPRESSIN Released in response to rising plasma tonicity or falling blood pressure Activates two subtypes of G protein coupled receptors: V1 - vascular smooth muscles and mediate o vasoconstriction V2 – renal tubule cells; REDUCE DIURESIS o through increased water permeability and water resorption in the collecting tubules. Secretion is regulated by the OSMOTIC PRESSURE of Body Fluids
ACTIONS: 1) 2) 3)
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Reduce water excretion by promoting concentration of urine Increase hydroosmotic permeability of cells in the distal tubules and medullary collecting ducts of the kidney Causes contraction of smooth muscle in blood vessels and in the GI tract INDUCE GLYCOGENOLYSIS IN THE LIVER Potentiate ACTH release by corticotropin-releasing factor
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LIPOLYSIS Breakdown of stored fats; CATABOLIC o Leads to increased circulating fatty acid levels, o reduced omental fat mass, and enhanced lean body mass PROMOTES GLUCOSE TOLERANCE Antagonizing insulin action o INDUCE PROTEIN SYNTHESIS AND NITROGEN RETENTION PROMOTES Na, K, and Water RETENTION Elevates serum levels of inorganic phosphate o STIMULATES EPIPHYSEAL PRECHONDROCYTE DIFFERENTIATION
CLINICAL CORRELATION ADH DIABETES INSIPIDUS •
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GH- Stimulation on Cartilage and Bone Growth Increase synthesis of DNA, RNA, Protein, HYDROXYPROLINE
Chondrocyte proliferation
Produce abnormally large volume of dilute urine Deficiency in VASOPRESSIN DESMOPRESSIN Structurally modified version of vasopressin o Intranasal or PO o More selective for V2 than V1 receptors o Longer duration and better potency than o vasopressin SE: Headache, N&V, abdominal cramps, allergy. o Overdosage: HYPONATREMIA and Seizures ADV: VASOPRESSIN (But not Desmopressin) can o cause VASOCONSTRICTION and should be used cautiously in patients with CORNOARY ARTERY DISEASE
HYPONATREMIA Cartilage proliferation •
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Widening of epiphyseal plate
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New bone laid down
Excess vasopressin secretion Results in production of decreased volume of more highly concentrated urine Results in excess water retention with expansion and dilution of body fluids. Syndrome of inappropriate antidiuresis CAUSES: Exogenous administration of ADH, Desmopressin, or large doses of Oxytocin. GROWTH HORMONE
Linear Growth until closure of Epiphyseal plate
DEFICIENCY CHILDREN SHORT STATURE o Micropenis o Increased fat o High pitched voice o •
FIGURE 6: GH Stimulation of Cartilage and Bone Growth
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ENDOCRINE SYSTEM o
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Propensity to hypoglycemia unopposed insulin action
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Reduced lean body mass Increased fat mass with selective deposition of intra-abdominal visceral fat Increased weigh to hip ratio Hyperlipidemia Left ventricular dysfunction HPN Increased plasma fibrinogen levels BONE MINERAL CONTENT IS REDUCED " with resultant increase in fracture rates
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SOMATROPIN Recombinant form of GH; subQ o MECASERMIN Children with growth failure (severe IGF-1 o deficiency) and unresponsive to exogenous Complex of recombinant human IGF-1 and o recombinant human IGF binding protein 3. subQ; 2x daily o SE: HYPOGLYC EMIA, intracr anial HPN, o asymptomatic elevation of liver enzymes
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BUT DOES NOT ACTIVATE IT" IT IS AN ANTAGONIST) SE Worsening of GH secreting pituitary # tumors Increase in levels of hepatic enzymes # (AST and ALT) REFERENCES
Katzung, Masters and Trevor BASIC AND CLINICAL TH PHARMACOLOGY 12 EDITION TH Guyton and Hall TEXTBOOK OF MEDICAL PHYSIOLOGY 11 EDITION, 2006 TH BERNE AND LEVY PHYSIOLOGY 6 EDITION TH SNELL CLINICAL ANATOMY 7 EDITION
EXCESS GROWTH HORMONE ACROMEGALY •
Abnormal growth of cartilage and bone tissue and many organs including skin, muscle, heart, liver, and the GI tract.
GIGANTISM •
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GH secreting adenoma occurs epiphyses close Rare condition
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SOMATOSTATIN Inhibits pituitary production of GH o Controls GH production o SHORT HALF LIFE as a drug (1-3 minutes) o OCTREOTIDE Somatostatin analogue o 45x more potent than somatostatin in inhibiting GH o release Twice as potent in reducing insulin secretion o SUBQ" q8 o IM " 4 week intervals o SE o N&V, Abdominal cramps, flatulence, # steatorrhea with bulky bowel movements Biliary sludge and gallstones # # Sinus bradycardia and conduction disturbances Pain at site of injection # B12 deficiency " long term use of # Octreotide PEGVISOMANT PEG derivative of mutant GH o Partially activates GH receptor " allowing o dimerization of the receptor but blocking the conformation changes for signal transduction. (IN SIMPLER TERMS, IT BINDS TO THE RECEPTOR
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