Hypothalamus pituitary-thyroid

Second ppt on endocrine system, describing hypothalamus, pituitary and thyroid glands.
This describes the hormones from these glands and their mode of action etc

1. Endocrine glands: Hypothalamus, pituitary & thyroid Radhakrishna G Pillai

2. Hypothalamus Hypothalamus is a major link between nervous and endocrine system Pituitary attached to hypothalamus by infundibulum Anterior pituitary or adenohypophysis Posterior pituitary or neurohypophysis

3. Anterior pituitary Release hormones by stimulatory or inhibitory messages from the hypothalamus Also regulated by negative feedback Hypothalamic hormones made by neurosecretory cells transported by hypophyseal portal system Anterior pituitary hormones that act on other endocrine systems are called tropic hormones

4. Anterior Pituitary Hormones Human growth hormone ( hGH ) or somatostatin Stimulates secretion of insulin-like growth factors (IGFs) that promote growth, protein synthesis Thyroid-stimulating hormone (TSH) or thyrotropin Stimulates synthesis and secretion of thyroid hormones by thyroid Follicle-stimulating hormone (FSH) Ovaries: initiates development of oocytes Testes: stimulates testosterone production

5. Anterior Pituitary Hormones Luteinizing hormone (LH) Ovaries: stimulates ovulation, Stimulate the production of oestradiol helps to control the menstrual cycle After fertilization, LH stimulate the corpus luteum which produces progesterone to sustain the pregnancy Men: luteinizing hormone stimulates the production of testosterone from Leydig cells in the testes Testosterone, in turn, stimulates sperm production and helps accentuate male characteristics — like deep voice or growth of facial hair

6. Anterior Pituitary Hormones Prolactin (PRL) Promotes milk secretion by mammary glands Adrenocorticotropic hormone (ACTH) or corticotropin Stimulates glucocorticoid secretion by adrenal cortex Melanocyte -stimulating Hormone (MSH) Unknown role in humans

7. Posterior pituitary Does not synthesize hormones Stores and releases hormones made by the hypothalamus Transported along hypothalamo-hypophyseal tract Oxytocin (OT) Antidiuretic hormone (ADH) or vasopressin

8. Hormones stored in Posterior pituitary Oxytocin During and after delivery of baby affects uterus and breasts Enhances smooth muscle contraction in wall of uterus Stimulates milk ejection from mammary glands

9. Antidiuretic Hormone (ADH) Decreases urine production by causing the kindeys to reabsorb more water to the blood Also decreases water loss through sweating and constriction of arterioles which increases blood pressure (vasopressin)

10. Thyroid Gland Located inferior to larynx 2 lobes connected by isthmus Thyroid follicles produce thyroid hormones Thyroxine or tetraiodothyronine (T 4 ) Triiodothyronine (T 3 ) Both hornones increase BMR Stimulate protein synthesis Increase use of glucose and fatty acids for ATP production Parafollicular cells or C cells produce calcitonin Lowers blood Ca 2+ by inhibiting bone resorption

11. Control of thyroid hormone secretion Thyrotropin -releasing hormone (TRH) from hypothalamus Thyroid-stimulating hormone (TSH) from anterior pituitary Increase in ATP demand also increase secretion of thyroid hormones

12. Control of Thyroid hormones The thyroid gland, anterior pituitary gland, and hypothalamus comprise a self-regulatory circuit known as hypothalamic-pituitary-thyroid axis

13. TSH release TRH acts via phosphatidylinositol 4-phosphate (PIP)- PKC and calcium signaling

14. Calcium signalling in TH production and release Calcium signaling involving phospholipase C is involved Calcium signaling is a process whereby the extremely low cytoplasmic Ca 2+  concentration increases in a deliberate and specific manner to trigger downstream cellular events Virtually every tissue, and even every cell type in the human body utilizes some form of Ca 2+  signaling to function or survive There are many mechanisms which can generate Ca 2+  signals The most widely encountered is a mechanism involving a lipid metabolizing enzyme phospholipase C

15. Phospholipase C signaling Only enzyme that can directly produce (or modulate) 3 distinct signals: inositol 1,4,5-trisphosphate (IP 3 ), diacylglycerol , and phosphatidylinositol 4,5-bisphosphate (PIP2) Initiating reaction is the breakdown of the lipid phosphatidylinositol 4,5 phosphate (PIP2) producing inositol 1,4,5 triphosphate This IP 3 function as a Ca 2+  signaling second messenger All three phospholipase C derived signals regulate ion channels Release of Ca 2+ from intracellular stores  (ER, microsomal fractions) Depletion of the endoplasmic reticulum Ca 2+  pool activate Ca 2+  influx from extracellular fluid through plasma membrane

16. TSH TSH is released into the blood TSH binds to the thyroid-stimulating hormone receptor (TSH-R) on the basolateral aspect of the thyroid follicular cell The TSH-R is a Gs-protein coupled receptor, and its activation leads to the activation of adenylyl cyclase and Increase in intracellular levels of cAMP The increased cAMP activates protein kinase A (PKA) PKA phosphorylates different proteins to modify their functions

17. Formation and release of T3 and T4 Monoiodotyrosine (MIT) and diiodotyrosine (DIT) are generated in thyrocytes MIT has a single iodine residue in tyrosine, and DIT has two iodine residues in tyrosine Thyroid peroxidase (TPO) combines iodinated tyrosine residues to make triiodothyronine (T3) and tetraiodothyronine (T4) One each of MIT and DIT join to form T3, and two DIT molecules form T4 Thyroid hormones are bound to thyroglobulin and stored in the follicular lumen

18. Release of thyroid hormones Thyrocytes uptake iodinated thyroglobulin via endocytosis Lysosome fuse with the endosome containing iodinated thyroglobulin Thyroglobulin is cleaved into MIT, DIT, T3, and T4 by Proteolytic enzymes in the endolysosomes T3 (20%) and T4 (80%) are released into the fenestrated capillary network via the transporter MCT8 Deiodinase enzymes remove iodine molecules from DIT and MIT Iodine can be salvaged and redistributed to an intracellular iodide pool

19. T3 & T4 Thyroxine  (T4) is the predominant secretory product of the thyroid gland Only 20% of the circulating T3 are secreted directly by the thyroid In the periphery T4 is deiodinated supplying roughly 80% of the circulating triiodothyronine (T3) Synthesis and release of T4 and T3 are inhibited when hormone levels in plasma exceed a pre-set level To a large extent, TRH defines this pituitary-thyroid axis set point and contributes to the maintenance of homeostasis of the plasma hormone levels In the pituitary TRH regulates not only the secretion of TSH but also its bioactivity required for correct receptor binding

20. Transport of Thyroid Hormones Thyroid hormones are lipophilic and circulate bound to the transport proteins Transporter proteins include thyroxine -binding globulin (TBG), transthyretin , and albumin Only a fraction (~0.2%) of the thyroid hormone (free T4) is unbound and active On reaching the target site, T3 and T4 can dissociate from their binding protein Enter cells either by diffusion or carrier-mediated transport

21. Receptor binding Thyroid receptors are transcription factors that can bind to both T3 and T4 They have a much higher affinity for T3 As a result, T4 is relatively inactive Deiodinases convert T4 to active T3 or inactive reverse T3 (rT3)

22. Physiological roles of Thyroid hormones Thyroid hormone affects virtually every organ system in the body In general, the thyroid hormone binds to its intra-nuclear receptor This activates the genes for increasing metabolic rate and thermogenesis Increasing metabolic rate involves increased oxygen and energy consumption

23. Physiological effects of thyroid hormones Increases the basal metabolic rate May induce lipolysis or lipid synthesis depending on metabolism Stimulate the metabolism of carbohydrates Anabolism/catabolism of proteins Permissive effect on catecholamines In children, thyroid hormones act synergistically with growth hormone to stimulate bone growth

24. Thyroid hormones on central nervous system During the prenatal period, thyroid hormones are needed for the maturation of the brain In adults, it can affect mood Hyperthyroidism can lead to hyper excitability and irritability Hypothyroidism can cause impaired memory, slowed speech, and sleepiness Thyroid hormone affects fertility, ovulation, and menstruation

25. Effect on different organs Heart: TH have a permissive effect on catecholamine It increases the expression of beta-receptors to increase heart rate, stroke volume, cardiac output, and contractility. Lungs: TH stimulate the respiratory centers: increase perfusion & increase oxygenation Skeletal muscles: increased development of type II muscle fibers These are fast-twitch muscle fibers capable of fast and powerful contractions

26. TH Physiological role Metabolism: TH increases the basal metabolic rate increases the gene expression of Na+/K+ ATPase in different tissues leading to increased oxygen consumption, respiration rate, and body temperature TH do not change the blood glucose level, but they can cause increased glucose reabsorption , gluconeogenesis , glycogen synthesis, and glucose oxidation. Growth during childhood TH act synergistically with growth hormone to stimulate bone growth It induces chondrocytes , osteoblasts , and osteoclasts Also helps with brain maturation by axonal growth and the formation of the myelin sheath

27. TH in action Receptors for T3 remain bound to the DNA in nucleus T3 /T4 then bind to nuclear α / β receptors in the tissue Cause activation of transcription factors Activation of certain genes and cell-specific responses TH are degraded in the liver via sulfation and glucuronidation Degraded products excreted in the bile

28. Radhakrishna G Pillai [email protected] 0091 9495554891 Thank You