The Endocrine System: Part 1

1. The Endocrine System: Part 1

2. Endocrine System: Overview Acts with nervous system to coordinate and integrate activity of body cells Influences metabolic activities via hormones transported in blood Response slower but longer lasting than nervous system Endocrinology Study of hormones and endocrine organs MDufilho

3. Endocrine System: Overview • Exocrine glands • Nonhormonal substances (sweat, saliva) • Have ducts to carry secretion to membrane surface • Endocrine glands • Produce hormones • Lack ducts MDufilho

4. Figure 16.1 Location of selected endocrine organs of the body. Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Gonads • Ovary (female) • Testis (male) MDufilho

5. Chemical Messengers • Hormones: long-distance chemical signals; travel in blood or lymph • Autocrines: chemicals that exert effects on same cells that secrete them • Paracrines: locally acting chemicals that affect cells other than those that secrete them • Autocrines and paracrines are local chemical messengers; not considered part of endocrine system MDufilho

6. Chemistry of Hormones • Two main classes • Amino acid-based hormones • Amino acid derivatives, peptides, and proteins • Steroids • Synthesized from cholesterol • Gonadal and adrenocortical hormones MDufilho

7. Mechanisms of Hormone Action • Though hormones circulate systemically only cells with receptors for that hormone affected • Target cells • Tissues with receptors for specific hormone • Hormones alter target cell activity MDufilho

8. Mechanisms of Hormone Action • Hormones act at receptors in one of two ways • Water-soluble hormones (all amino acid–based hormones except thyroid hormone) • Act on plasma membrane receptors • Act via G protein second messengers • Cannot enter cell 2. Lipid-soluble hormones (steroid and thyroid hormones) • Act on intracellular receptors that directly activate genes • Can enter cell MDufilho

9. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Slide 1 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) cAMP activates protein kinases. 5 cAMP GTP Receptor GTP ATP Active protein kinase Inactive protein kinase GDP GTP Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 3 4 Receptor activates G protein (Gs). G protein activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP (2nd messenger). MDufilho

10. Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Slide 1 Steroid hormone Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Receptor Binding region Nucleus 3 The receptor- hormone complex binds a specific DNA region. DNA 4 Binding initiates transcription of the gene to mRNA. mRNA The mRNA directs protein synthesis. 5 New protein MDufilho

11. Target Cell Specificity • Target cells must have specific receptors to which hormone binds, for example • ACTH receptors found only on certain cells of adrenal cortex • Thyroxin receptors are found on nearly all cells of body MDufilho

12. Target Cell Activation • Target cell activation depends on three factors • Blood levels of hormone • Relative number of receptors on or in target cell • Affinity of binding between receptor and hormone MDufilho

13. Target Cell Activation • Hormones influence number of their receptors • Up-regulation—target cells form more receptors in response to low hormone levels • Down-regulation—target cells lose receptors in response to high hormone levels MDufilho

14. Control of Hormone Release • Blood levels of hormones • “Controlled” by negative feedback systems • Vary only within narrow, desirable range • Endocrine gland stimulated to synthesize and release hormones in response to • Humoral stimuli • Neural stimuli • Hormonal stimuli MDufilho

15. Figure 16.4a Three types of endocrine gland stimuli. Slide 1 Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+. MDufilho

16. Figure 16.4b Three types of endocrine gland stimuli. Slide 1 Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine. MDufilho

17. Figure 16.4c Three types of endocrine gland stimuli. Slide 1 Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Gonad (Testis) Adrenal cortex Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones. MDufilho

18. Nervous System Modulation • Nervous system modifies stimulation of endocrine glands and their negative feedback mechanisms • Example: under severe stress, hypothalamus and sympathetic nervous system activated •  body glucose levels rise • Nervous system can override normal endocrine controls MDufilho

19. Hormones in the Blood • Hormones circulate in blood either free or bound • Steroids and thyroid hormone are attached to plasma proteins • All others circulate without carriers • Concentration of circulating hormone reflects • Rate of release • Speed of inactivation and removal from body MDufilho

20. Interaction of Hormones at Target Cells • Multiple hormones may act on same target at same time • Permissiveness: one hormone cannot exert its effects without another hormone being present • Synergism: more than one hormone produces same effects on target cell  amplification • Antagonism: one or more hormones oppose(s) action of another hormone MDufilho

21. Amino Acid based hormones • Water soluble • May be stored and release later • Most are free – metabolized quickly • Shorter half-live • Example – Amino acid based hormones except Thyroxin MDufilho

22. Steroid Homones • Lipid-soluble • Cannot be stored • Transported by plasma proteins • Half life is longer • Less fluctuation in blood • Example: Estrogen, progesterone, testosterone, aldosterone, corticol MDufilho

23. The Pituitary Gland and Hypothalamus Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe) Neural tissue Anterior pituitary (lobe) (adenohypophysis) Glandular tissue MDufilho

24. Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Slide 1 Paraventricular nucleus Hypothalamus 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). Posterior lobe of pituitary Optic chiasma Supraoptic nucleus Infundibulum (connecting stalk) 2 Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary. Inferior hypophyseal artery Hypothalamic- hypophyseal tract Axon terminals 3 Oxytocin and ADH are stored in axon terminals in the posterior pituitary. Posterior lobe of pituitary 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. Oxytocin ADH MDufilho

25. Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Slide 1 Hypothalamus Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. Anterior lobe of pituitary Superior hypophyseal artery 1 When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus. 2 Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary. Hypophyseal portal system • Primary capillary plexus A portal system is two capillary plexuses (beds) connected by veins. 3 In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation. • Hypophyseal portal veins • Secondary capillary plexus GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary MDufilho

26. Posterior Pituitary and Hypothalamic Hormones • Oxytocin and ADH • Each composed of nine amino acids • Almost identical – differ in two amino acids • What are the actions of Oxytocin? • How about ADH? MDufilho

27. ADH (Vasopressin) • Inhibits or prevents urine formation • Primary purpose water balance – osmolarity of body fluids – normal 285 – 300 milliosmols • Targets kidney tubules  reabsorb more water • Release also triggered by pain, low blood pressure, and drugs • Inhibited by alcohol, diuretics • High concentrations  vasoconstriction MDufilho

28. Determining Osmolality • Osmolality = concentration based on # solutes/liter • Lab reports do not show osmolality – show electrolyte concentration – need to double Na+ concentration • Hypertonicity = >300 mOsm • Edema = <285 mOsm • Osmoreceptors respond to change in osmolality of plasma MDufilho

29. ADH • Diabetes insipidus • ADH deficiency due to hypothalamus or posterior pituitary damage • Must keep well-hydrated • Syndrome of inappropriate ADH secretion (SIADH) • Retention of fluid, headache, disorientation • Fluid restriction; blood sodium level monitoring MDufilho