Endocrine Part 8 Growth Hormone and Thyroid Hormone PDF

Endocrine Part 8 Growth Hormone and Thyroid Hormone PSL300 Helen Miliotis, PhD  Growth Control and Thyroid Lecture outline Hypothalamic/Pituitary Axis Growth Hormone - synthesis and action - actions on bone and metabolism - pathologies Thyroid Hormone -...

Endocrine Part 8 Growth Hormone and Thyroid Hormone PSL300 Helen Miliotis, PhD  Growth Control and Thyroid Lecture outline Hypothalamic/Pituitary Axis Growth Hormone - synthesis and action - actions on bone and metabolism - pathologies Thyroid Hormone - synthesis and regulation - actions on development and metabolism - pathologies Textbook reading:Silverthorn 8th ed. 205-212, 734-743 (7th ed. 209-215, 736-745)(6th Ed. 782-793, 219-225) (5th 764- 772, 221-232)  Hypothalamus - Pituitary Hypothalamus Pituitary gland is two glands fused in one Posterior pituitary is neural tissue and secretes two neurohomones: vasopressin (antidiuretic hormone or ADH) and oxytocin Anterior pituitary is endocrine tissue and secretes six hormones: prolactin, thyrotropin, adrenocorticotropin, growth hormone, follicle- stimulating hormone, and luteinizing hormone © 2016 Pearson Education, Inc. Figure 7.8c The Pituitary Gland The posterior pituitary is an extension of the brain that secretes neurohormones made in the hypothalamus. HYPOTHALAMUS Neurohormone is made and packaged in cell body of neuron. Vesicles are transported down the cell. Vesicles containing neurohormone are stored in posterior pituitary. POSTERIOR PITUITARY Vein Neurohormones are released into blood. Oxytocin Vasopressin Ile Gln Phe Gln Tyr Asp Asp Tyr Cys Cys Cys Cys Gly Gly Pro Leu Pro Arg Mammary glands and uterus Kidneys © 2016 Pearson Education, Inc. Figure 7.8b The Pituitary Gland The anterior pituitary is a true endocrine gland that secretes six classic hormones. Neurohormones from the hypothalamus control release of the anterior pituitary hormones. The hypothalamic hormones reach the anterior pituitary through a specialized region of the circulation called a portal system. Neurons synthesizing HYPOTHALAMUS trophic neurohormones release them into capillaries of the portal system. Capillary bed Portal veins carry the trophic neurohormones Artery directly to the anterior pituitary, where they act on the endocrine cells. POSTERIOR PITUITARY Endocrine cells release Capillary bed their peptide hormones into the second set of ANTERIOR PITUITARY capillaries for distribution to the rest of the body. Veins TO TARGET ORGANS Prolactin Gonadotropins (LH & FSH) GH ACTH TSH Ovary Testis Mammary glands Musculoskeletal system Thyroid gland Adrenal cortex Gonads © 2016 Pearson Education, Inc. Figure 7.9 Hormones of the Hypothalamic-Anterior Pituitary Pathway © 2016 Pearson Education, Inc. Growth  GHRH stimulates GH release GH stimulates IGF-1 release  What is IGF-1? Insulin-Like Growth Factor (IGF-1) GH acts on the liver to secrete IGF-1 - growth-promoting effects on almost every cell in the body Growth hormone (GH) stimulates bone growth GH liver IGF-I Chondrocytes: recruitment proliferation matrix IGF-1 = insulin-like growth factor 1  Question What would you expect to see in a person with too much growth hormone because of a pituitary tumor? a) Decreased osteoblast activity in bone tissue b) Increased number of chondrocytes c) Decreased IGF-1 d) Increased levels of growth hormone releasing hormone (GHRH)  Growth, a complex process, depends on: Diet and genetics Hormones and growth factors – Growth hormone and insulin-like growth factor 1 – Thyroid hormones – Insulin – Sex steroids – Cortisol  Gigantism = too much GH in childhood Acromegaly = too much GH in adulthood Key concepts for Growth Hormone (GH) Normal growth requires: GH, thyroid hormones, insulin, and sex hormones Adequate nutrition, no chronic stress Anterior pituitary secretes GH Stimulates IGF-1 to promote bone and soft tissue growth GH is regulated by: Stimulated by GHRH Inhibited GHIH (aka somatostatin) Thyroid Hormone Figure 23.4c Thyroid hormone synthesis Slide 1 Thyroid hormones are made from iodine and tyrosine. + Blood Na T3 T4 A Na+-I symporter brings Free T3 and T4 I into the cell. The pendrin NIS enter the circulation. transporter moves I into the colloid. T3 T4 Follicular cell synthesizes Protein enzymes and thyroglobulin synthesis for colloid. Intracellular enzymes separate T3 and T4 Enzymes, from the protein. Thyroglobulin T3 T4 Follicular Pendrin cells Thyroglobulin is Tyrosine taken back into the cell in vesicles. Thyroid peroxidase adds iodine to tyrosine to make Thyroglobulin T3 and T4. Triiodothyronine (T3) 2 tyrosine + 3 Thyroxine (T4) 2 tyrosine + 4 MIT + tyrosine DIT + MIT T3 MIT + DIT KEY T4 DIT + DIT MIT = monoiodotyrosine DIT = diiodotyrosine T3 = triiodothyronine Colloid T4 = thyroxine © 2016 Pearson Education, Inc.  What is the mechanism of action of thyroid hormones? T3 and T4 circulate in blood bound to plasma proteins T3 more 3-5X more potent than T4 T4 converted to T3 in target tissues Both bind to nuclear thyroid receptors (form homodimers or heterodimers with retinoic acid receptor) Alter gene transcription  What are the functions of thyroid hormones? Metabolic (hmetabolic rate, hoxygen consumption, hheat production, hprotein degradation, hlipolysis) Nervous system (enhances speech, thinking, reflexes) Growth and development (essential in children, works with GH) Cardiovascular (enhances heart rate and contractility; peripheral blood flow, works in part by increasing numbers of  adrenergic receptors + other proteins) Muscular (too much causes muscle weakness)  Key concepts for Thyroid Hormones (T3 and T4) Thyroid hormone secretion from the thyroid gland is controlled by: TRH from the hypothalamus TSH from the anterior pituitary Thyroid hormones are made in the follicle, from tyrosine and iodine to form T3 and T4 Thyroid hormones influence metabolic rate, and protein, fat, and carbohydrate metabolism  Thyroid hormone disorders Hyperthyroidism: Thyroid hormone excess Disorders Causes: tumours thyroid-stimulating immunoglobulins (Graves’ disease) Symptoms: goiter, nervousness, insomnia, anxiety, high heart rate, exophthalmos (Graves’ disease), weight loss. Treatments: removal of part of the thyroid gland, drugs blocking synthesis of T3 and T4 or block conversion of T4 to T3  Graves' disease Autoimmune disease: Abnormal antibodies against the TSH receptor are produced Cause unknown Most common cause of hyperthyroidism Most common cause of general thyroid enlargement in developed countries Normal Enlarged (goiter) https://www.nlm.nih.gov/ http://www.bio.davidson.edu/Courses/Immunology/Students/Spring2003/Breedlove/GravesDisease.html  Thyroid hormone disorders cont’d Hypothyroidism: Thyroid hormone deficiency Causes: under active thyroid gland lack of iodine in diet - Symptoms: goiter, slowed heart rate, slowed speech, fatigue, cold-intolerance, cretinism (infants), stunted growth (infants) and weight gain. Cretinism (infants) Treatments: exogenous thyroid hormone T4 (thyroxine)  Iodine deficiency Iodine deficiency leaves the thyroid gland unable to produce T4 and T3 Lack of negative feedback leads to excess TSH secretion TSH stimulates growth of the thyroid gland, goiter may be present 2 billion people world wide deficient of iodine 50 million with symptoms 5 cents/YEAR to supply enough for each person  Review Question #2: A man is iodine deficient. Predict his levels of TRH, TSH and TH (T3 and T4) secretion in comparison to normal Review  Review Question #2: A man is iodine deficient. Predict his levels of TRH, TSH and TH (T3 and T4) secretion in comparison to normal Review