Human physiology part 6


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Human physiology part 6

  1. 1. Principles of Hormonal Control Systems (Part 6)<br />Chapter 10 John Paul L. Oliveros, MD, DPPS<br />
  2. 2. Summary of Hormones<br />
  3. 3.
  4. 4. Hormone structure and synthesis<br />3 chemical classes of hormones<br />Amines<br />Peptides and proteins<br />steroids<br />Amine Hormones<br />Derivatives of tyrosine<br />Include:<br />Thyroid hormones<br />Epinephrine<br />Norepinephrine<br />dompamine<br />Thyroid Hormones<br />Thyroxine (T4) and Triiodothyronine<br />Secreted by thyroid follicles<br />Iodine<br />Essential element of thyroid hormones<br />Food  GI tract  blood (converted to iodide)  thyroid follicular cells (conversion back to iodine)  thyroglobulin (incorportation with tyrosine and thyroglobulin precursor) <br />Thyroglobulin<br />Found in central spaces between thyroid follicles<br />Endocytosis into follicular cells and digested by lysosymes to release thyroid hormones<br />
  5. 5. Thyroid Hormones<br />Thyroxine (T4)<br />Secreted in large amounts<br />Converted into T3 by most tissue by deiodination<br />Has no action unless converted to T3<br />Persons with defective deiodination enzyme manifest as thyroid hormone deficiencyeven with normal or increased T4<br />Triiodothyroxine (T3)<br />More active than T4<br />Function:<br />Regulation of O2 consumption<br />Growth<br />Brain development and function<br />
  6. 6. Adrenal Medulla Glands and Dopamine<br />Adrenal gland<br />Adrenal cortex<br />Adrenal medulla<br />Modified sympathetic ganglion<br />Axons release secretions into blood (endocrine)<br />Secrete 2 amine hormones<br />Epinephrine (E)<br />Secreted 4x more than NE<br />Norepinephrine (NE)<br />Dopamine<br />Secreted by cells in the hypothalamus<br />Function as a hormone<br />Also secreted by small amounts in the adrenal glands<br />
  7. 7. Peptide Hormones<br />Composes majority of hormones<br />preprohormones (ribosomes) prohormones (endoplasmic reticulum)  hormones + peptides (golgi apparatus)<br />Many also functions as neurotransmitters/ neuromodulators<br />
  8. 8. Steroid Hormones<br />Produced by the adrenal cortex and gonads, placenta<br />Cholesterol<br />Steroid produced on a particular cell depends on the types and concentration of enzymes present<br />Highly soluble<br />Steroid producing cell  plasma membrane  interstital fluid blood  binding with plasma proteins<br />
  9. 9. Hormones of the adrenal cortex<br />Aldosterone<br />Mineralocorticoid<br />Salt (mineral) balance<br />Kidney’s handling of Na+, K+, H+ ions<br />Cortisol and Corticosterone<br />Glucocorticosteroid<br />Metabolism of glucose and other organic nutrients<br />Facilitation of response to stress<br />Regulation of immune system<br />Dehydroepiandrosterone (DHEAS) and Androstenedione<br />Androgens<br />Include testosterone (testes)<br />Other adrenal androgens function like testosterone but less potent<br />Play important role in adult female and both sexes during puberty<br />
  10. 10. Hormones of the adrenal cortex<br />3 distinct layers of adrenal cortex<br />Zona glomerulosa<br />High enzyme concentration to convert corticosterone to aldosterone<br />Zona fasciculata<br />Zona reticularis<br />Secretes more androgen and cortisol<br />If less enzyme for conversion to cortisol, may produce masculinzation in females<br />
  11. 11. Hormones of the Gonads<br />High concentrations of enzymes to lead to androstenedione<br />Testes<br />Androstenedione  testosterone<br />Ovaries<br />High concentrations of aromatase <br />Androgens  estradiol<br />Some ovarian cells screte progesterone<br />
  12. 12. Hormone transport in blood<br />Concentration of free hormone is more physiologically important than total concentration<br />
  13. 13. Hormone Metabolism and Excretion<br />Liver and kidneys<br />Major organs for hormone excretion and metabolism<br />Target cells<br />May metabolize cetain peptide hormones<br />Plasma/blood<br />Rapid elimination of peptide hormones and catecholamines<br />Less rapid elimination of protein bound hormones (thyroid and steroid hormones)<br />Metabolism may activate some hormones instead of inactivating them<br />
  14. 14. Mechanisms of Hormone action<br />Hormone receptors<br />Ability to respond depends on the ability of receptors for a homrone on the target cell<br />Receptors<br />Catecholamines/peptide hormones<br />Plasma membrane receptors<br />Steroid/thyroid hormones<br />Intracellular receptors<br />Hormone Receptors<br />Permissiveness<br />Hormone A must be present for the full strength of hormone B’s effect<br />
  15. 15. Mechanisms of Hormone Action<br />Effects of peptide hormones and catecholamines<br />Activated receptors directly influence either of the folowing:<br />Ion channels that are part of the receptor<br />Enzyme activity that is part of the receptor<br />Acivity of JAK kinases associated with the receptor<br />G-proteins coupled in the plasma membrane to effector proteins(ion channels and enzymes) that generate 2nd messengers<br />
  16. 16. Mechanisms of Hormone Action<br />Effect of steroids and thyroid hormones<br />Steroid hormones, thyroid hormones, Vit D are closely related<br />Steroid hormone receptor superfamily<br />Binding of hormone with receptor causes activation/inhibition of particluar gene change in rate of protein synthesis coded by genes<br />
  17. 17. Inputs that control Hormone Secretion<br />Most are released in short burst<br />Some are release in cycles<br />Controlled mainly by<br />Changes in plasma concentration of ions and nutrients<br />Neurotransmitters released from impinging neurons<br />Another hormone acting on the endocrine cell<br />In most cases, hormone secretion is influenced by more than 1 input<br />
  18. 18. Inputs that control Hormone Secretion<br />Control by plasma concentrations of mineral ions or organic nutrients<br />Major function of hormone is to regulate (negative feedback) the plasma ion or nutrient controlling its secretion<br />
  19. 19. Inputs that control Hormone Secretion<br />Control by neurons<br />Adrenal medulla behaves like a sypathetic ganglion<br />Other endocrine glands controlled by autonomic nervous system<br />Examples:<br />Insulin<br />Other gastrointestinal hormones<br />
  20. 20. Inputs that control Hormone Secretion<br />Control by other hormones<br />Secretion of a particular hormone is directly controlled by the blood concentration of another hormone<br />Trophic hormone<br />A hormone that stimulates the secretion of another hormone<br />Usually stimulate growth of the stimulated gland<br />
  21. 21. Control Systems Involving the Hypothalamus and Pituitary<br />Pituitary gland<br />Anterior pituitary<br />AKA adenohypophysis<br />With hypothalamo-pituitary portal vessels<br />Local route for blood flow directly from hypothalamus to anterior pituitary<br />Posterior pituitary<br />AKA neurohypophysis<br />Outgrowth of the hypothalamus<br />Neural tissue<br />Axons that end near posterior pituitaryfrom hypothalamic nucleus<br />Supraoptic nuclei<br />Paraventricular nuclei<br />
  22. 22. Posterior Hypothalamus<br />Hormones secreted are synthesized in the hypothalamus<br />Hormones travel to posterior pituitary enclosed in small vesicles<br />Stimuli (hormones/neurotransmitter) action potentials  axon terminals  exocytosis of hormones<br />2 posterior pitutary hormones<br />Oxytocin<br />Acts on smooth muscles in breast and uterus<br />Vasopressin<br />AKA anti-diuretic hormone<br />Control of water excretion by the kidneys<br />Control of blood pressure<br />
  23. 23. The hypothalamus and anterior pituitary <br />Hypophysiotropic hormones<br />AKA hypothalamic releasing hormones<br />Hormones from the hypothalamus that influence the anterior pituitary <br />1st of the 3 hormone sequence<br />Hypophysiotropic hormone<br />Anterior pituitary hormone<br />Endocrine gland hormone<br />
  24. 24. Anterior Pituitary Hormones<br />Anterior pituitary secretes 8 hormones<br />Only 6 functional/classical hormones<br />Follicle-Stimulating Hormone (FSH)<br />Luteinizing Hormone (LH)<br />Growth Hormoe (GH)<br />Thyroid stimulating hormone (TSH/thyrotropin)<br />Prolactin<br />Adrenocorticotropic hormone (ACTH/corticotropin)<br />Gonadotropic hormones<br />FSH<br />LH<br />2 peptide hormones with unknown functions<br />B-lipotropin<br />B-endorphin<br />
  25. 25. Hypophysiotropic Hormones<br />Hypothalamic hormones that regulate secretion of anterior pituitary hormones<br />Axons that secrete these hormones terminate in the median eminence around the hypothalamo-pituitary portal vessels<br />Difference with posterior pituitary hormone<br />Neurons remain at the hypothalamus, ending at its median eminence<br />Hypophysiotropic hormones enter median eminence capillaries  hypothalamo-pituitary portal vessels anterior pituitary hormone<br />Anterior pituitary exposed to high concentrations of hypophysiotrophic hormones<br />
  26. 26. Hypophysiotrophic hormones<br />
  27. 27. Hypophysiotrophic Hormones<br />
  28. 28. Hypophysiotropic Hormones<br />Neural control<br />Hypothalamus receive synaptic input from virtually all areas of the CNS<br />Large number of neurotransmitters are relased on synapses of hormone secreting hypothalamic neurons<br />Secretion of hypophysiotropic hormones can be influenced by drugs that influence neurotransmitters<br />
  29. 29. Hypophysiotropic Hormones<br />Hormonal Control of the hypothalamus and anterior pituitary<br />Negative feedback (prominent feature of each sequence)<br />Effectivein dampening hormonal response / limiting extremes of hormonal secretory rates<br />Maintain plasma concentrations of the final hormone in a sequence constant whenever a disease-induced primary change occurs in the secretion or metabolism of the hormone<br />
  30. 30. Hypophysiotropic Hormones<br />Long-loop negative feedback<br />3rd endocrine gland exerts negative feedback effect on the hypothalamus/anterior pituitary gland<br />Exists on each of the 5 three-hormone sequences initiated by a hypophysiotropic hormone<br />Short-loop negative feedback<br />influence of an anterior pituitary hormone on the hypothalamus<br />
  31. 31. Role of “nonsequence” hormones on hypothalamus/anterior pituitary<br />Hormone that is not itself in a particular sequence influences hypothalamus and anterior hormone secretion<br />e.g. Estrogen enhances secretion of prolactin<br />
  32. 32. Candidate Hormones<br />Suspected hormones in humans butare not considered as classical hormones because<br />Functions have not been conclusively documented<br />Have well documented function in as paracrine/autocrine agent<br />Not certain if they reach target cell via blood<br />Melatonin<br />Produced by the pineal gland<br />Probably important in the setting of the body’s circadian rythms and sleep<br />Ability to reduce jetlag<br />Relationship to seasonal affective disorder (“winter depression”)<br />Potentials:<br />Natural sleeping pill<br />Scavenge free radicals<br />Control of the reproductive system<br />
  33. 33. Endocrine Disorders<br />Types:<br />Hyposecretion<br />Too little hormone<br />Hypersecretion<br />Too much hormone<br />Hyporesponsiveness<br />Reduced response of target cells<br />Hyperresponsiveness<br />Increase response of target cells<br />Hyposecretion<br />Primary hyposecretion<br />Gland is not able to function normally<br />Examples:<br />Decrease cortisol due to genetic absence of a steroid -forming enzyme in adrenal cortex<br />Decrease thyroid hormones due to dietary deficiency of iodine<br />Damage of an ndocrine gland due to:<br />Infection<br />Toxic chemicals<br />
  34. 34. Endocrine Disorders<br />Hyposecretion<br />Secondary hyposecretion<br />Gland secreting too little hormonebecause there is not enough tropic hormone<br />Example:<br />Decreased TSH (ant. Pituitary)  decreased thyroid hormone<br />Tertiary Hyposecretion<br />Decreased hormone secretion from hypothalamus<br />Example:<br />Dec TRH  dec TSH  dec thyroid hormones<br />Hyposecretion:<br />Diagnosis<br />Determine concentration of a hormone in the plasma or urine<br />Measure concentration of a tropic hormone to distinguish between primary and secondary hyposecretion<br />Administering tropic hormone or substance known to elicit secretion of a hormone<br />Primary defect: less than normalincrease in hormone<br />Secondary defect: normal increase in hormone<br />Treatment<br />Administering missing or deficient hormone<br />
  35. 35. Endocrine Disorders<br />Hypersecretion<br />Primary hypersecretion<br />Gland secreting too much of the hormone on its own<br />Most common cause:<br />Hormone-secreting endocrine cell tumor<br />Secondary hypersecretion<br />Excessive stimulation of a gland by its tropic hormone<br />Tertiary hypersecretion<br />Hypersecretion of a hypophysiotropic hormone (hypothalamus)<br />Hypersecretion<br />Diagnosis<br />Measure concentration of a hormone and its tropic hormone (blood/urine)<br />Secondary hypersecretion<br />Concentration of both hormone and topic hormone elevated<br />Primary hypersecretion<br />Decreased secretion of a tropic hormone because of negative feddback <br />Tertiary hypersecretion<br />Increase in hypophysiotropic hormone<br />Treatment<br />Surgical removal or radiation destruction of a endocrine tumor<br />Inhibitory drugs on hormon’s synthesis<br />Drugs that block hormone’s effect on target cells<br />
  36. 36. Endocrine Disorders<br />Hyporesponsiveness<br />Target cells do not respondnormally to a hormone<br />Types<br />Deficiency of receptors for the hormone<br />Events after hormone binding is defective<br />Lack or deficiency of enzymes that catalyzes activation of a hormone<br />Diagnosis:<br />Plasma concentration of hormones are normal or elevated despite diminished response of target cells<br />Examples<br />Diabetes mellitus (sugar diabetes)<br />Target cells are hyporesponsive to insulin<br />Hyperresponsiveness<br />Thyroid hormone cause up-regulation of certain receptors of epinephrine<br />Tachycardia in hyperthyroidism<br />
  37. 37. The End<br />