5.2 Pituitary Hormones and Their Control by the Hypothalamus 23.pdf

Pituitary Hormones and Their Control by the Hypothalamus Lecture Outline I. Pituitary gland its relation to the hypothalamus II. Hypothalamus controls pituitary secretion III. Physiological functions of growth hormone IV. Posterior pituitary gland and its relation to the hypothalamus 1 Pituitary Hor...

Pituitary Hormones and Their Control by the Hypothalamus Lecture Outline I. Pituitary gland its relation to the hypothalamus II. Hypothalamus controls pituitary secretion III. Physiological functions of growth hormone IV. Posterior pituitary gland and its relation to the hypothalamus 1 Pituitary Hormones and Their Control by the Hypothalamus Objectives 1. Describe the gross anatomy of the pituitary gland including its location and divisions 2. Compare and contrast the synthesis, secretory products, and release of hormones of the anterior and posterior pituitary 3. Compare the function of the tropic hormones of the anterior pituitary and the two hormones of the posterior pituitary 4. Explain the hypothalamic-hypophysial portal system 5. Explain the hypothalamic-pituitary axis and list three specific axes 6. Identify hypothalamic hormones and how they affect tropic hormones 7. Identify the stimulation and negative feedback control of growth hormone and the somatotropic axis 8. Explain the relationship of IGF-1 and GH and compare their functions 9. Identify factors relative to GH secretion including factors that both increase and decrease GH secretion 10. Identify pathophysiology related to excess and insufficient GH release 11. Identify the location, stimulation, of posterior pituitary hormones ADH and OT 12. List the physiologic effects of ADH and OT 13. Describe alterations of ADH secretion 2 References Assigned reading from your text: Hall Chapter 76 3 I. Pituitary Gland Its Relation to the Hypothalamus 4 Pituitary Gland Anatomy ❑ The pituitary gland- aka the hypophysis (“hypophysis” –pituitary) Is a 1 cm (diameter) gland Is connected to the hypothalamus via the hypophysial stalk ❑ The entire gland resides in the sella turcica of the sphenoid bone A pituitary tumor can press on the optic chiasm and cause blindness Transsphenoidal hypophysectomy is the surgical removal of pituitary tumors through the nose 5 Anterior and Posterior Lobes of the Pituitary Gland ❑ Comprised of two major components: Anterior pituitary Synthesizes and secretes 6 major peptides aka- adenohypophysis ”adeno” – gland Secretion controlled by hypothalamic hormones Hypothalamic-hypophysial portal system Embryologically from Rathke’s pouch An invagination of the oropharynx Posterior pituitary Secretes two hormones synthesized by cell bodies in the hypothalamus aka- neurohypophysis “neuro”- nerve Secretion controlled by nerve signals from the hypothalamus Hypothalamus, infundibulum, and posterior pituitary form an anatomical continuity Embryologically from an outgrowth of the hypothalamus Pars intermedia separates the two lobes of the pituitary 6 Anterior Pituitary Gland Cells Produce Tropic Hormones ❑ Tropic definition- “developing in response to” ❑ Hormones of the anterior pituitary gland are released by specific cells types Somatotropes produce Growth hormone Stomatotropin Promotes growth of most body tissues/cells ~40% of secretory cells of anterior pituitary Corticotropes produce Adrenocorticotropic hormone ACTH is aka corticotropin Controls secretion of adrenocortical hormones Control metabolism Thyrotropes produce Thyroid-stimulating hormone Thyrotropin Controls secretion of T3 and T4 Controls intracellular reactions in most cells Lactotropes produce Prolactin Promotes mammary glands and milk production Gonadotropes produce Gonadotropic hormones Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Control growth and activity of ovaries and testes 7 Posterior Pituitary Gland Releases Two Hormones Cell bodies are primarily located in the supraoptic nucleus (SON) and the paraventricular nucleus of the hypothalamus (PVN) Antidiuretic hormone Aka vasopressin Controls water excretion and BP Primarily formed in SON Oxytocin (Pitocin) Contracts pregnant uterus and lactation Formed primarily in PVN Hormone release is regulated by physiological response-driven negative feedback and local release of peptides. Copyright ©2002 American Physiological Society 8 II. Hypothalamus controls pituitary secretion 9 Hypothalamus Controls Many Endocrine Organs ❑ Hypothalamus coordinates the endocrine system via three mechanisms: 1. Hypothalamic neurons synthesize two hormones Antidiuretic hormone (aka vasopressin) Oxytocin 2. Secretes regulatory hormones that control secretion of endocrine cells of the anterior pituitary 3. Autonomic centers exert direct neural control over the endocrine cells of the adrenal medulla 10 Hypothalamic-Hypophysial Portal Blood Vessels of the Anterior Pituitary ❑ The hypothalamic-hypophysial portal system Hypothalamus is indirectly connected to the anterior pituitary by vessels An artery enters the hypothalamic area eventually forming a system of capillaries Capillaries fuse into venule portal vessels that supply the anterior pituitary by the infundibulum and form a group of secondary capillaries in the anterior pituitary These fuse into venules which empty into the venous system 11 Anterior Pituitary Regulatory Hormones Are Released From The Median Eminence ❑ Releasing hormone is delivered to the anterior pituitary and binds to specific receptors on the plasma membrane Initiates a G-protein/cAMP response The releasing hormone can stimulate an increased rate of hormone synthesis by specific anterior pituitary cells and stimulate secretion of the cells by Ca+2-induced exocytosis 12 Anterior Pituitary and Endocrine Axis Control ❑ Hypothalamic-pituitary axis Hypothalamus controls secretion of pituitary hormones by releasing (or inhibiting) factors Pituitary releases tropic hormones Peripheral gland releases target hormone ❑ CNS regions that project to hypothalamic neuroendocrine cells can regulate each axis Allows each axis to function independently Short-loop feedback describes negative feedback from pituitary on the hypothalamus eg GH inhibits GHRH release Long-loop feedback describes negative feedback from a target gland on the hypothalamus eg cortisol inhibits CRH release 13 Hypothalamic-Pituitary Axis ❑ Hypothalamus controls secretion of anterior pituitary hormones by releasing factors eg Hypothalamic-pituitary-adrenal axis (HPA Axis) secretes ACTH and cortisol secretion The HPA axis regulates body’s response to stress ❑ These axes are named with target gland Hypothalamic-pituitary- adrenal axis (shown) Hypothalamic-pituitary- gonadal axis Hypothalamic-pituitary- thyroid axis 14 Hypothalamic Hormones Control Anterior Pituitary Hormones ❑ Hypothalamic releasing and inhibitory hormones are secreted into the median eminence Nerves secrete releasing and inhibiting hormones into tissue fluids Hormones absorbed into the hypothalamic-hypophysial portal system – to anterior pituitary Thyrotropin-releasing hormone (TRH) –causes release of TSH Corticotropin-releasing hormone (CRH)- causes release of ACTH GH Growth hormone-releasing hormone (GHRH) causes release of GH Growth hormone-inhibiting hormone (GHIH), aka somatostatin, inhibits GH release Gonadotropin-releasing hormone (GnRH) causes release of LH and FSH Prolactin Prolactin inhibitory hormone (PIH), aka dopamine, causes inhibition of prolactin Prolactin is the only hormone predominantly under negative control from hypothalamus 15 Hypothalamic-Neurohypophyseal (Posterior) Axis ❑ Hypothalamus, infundibulum, and posterior pituitary form an anatomical continuity – the hypothalamic-neurohypophyseal axis Posterior pituitary consists of glial cells, axons, and nerve endings whose cell bodies are found in the median eminence of the hypothalamus These large cell bodies- magnocellular neuoronssynthesize posterior pituitary hormones Axons from these neurons pass from the respective nuclei through the infundibulum (neurohypophyseal stalk) to the posterior pituitary gland 16 Hypothalamic-Pituitary Axis 17 Boron Figure 47-3 III. Physiological Functions Of Growth Hormone 18 Growth Hormone ❑ All anterior pituitary hormones affect specific target organs/ tissues except GH – Widespread effects on most body tissues ❑ The somatotropic axis controls the release of Growth Hormone (GH) which: Stimulates growth from infancy through adulthood And helps mark specific developmental phases in the organism’s life After growth ceases, GH continues to be secreted until 50-60 years of age when secretion declines 19 The Somatotropic Axis ❑ The somatotropic axis controls the release of Growth Hormone (GH) which regulates growth in early development and helps mark specific developmental phases in the organism’s life Different from other axis systems – No tropic hormone released by the anterior pituitary Liver is the only endocrine target (GH) Production of GH is regulated by two hormones from the hypothalamus: – Growth hormone releasing hormone (GHRH) neurons stimulate somatotropes – Somatostatin (SS) from the anterior hypothalamus neurons inhibit somatotropes GH stimulates the liver to synthesize insulin-like growth factor-1 (IGF-1) – IGF-1- aka somatomedin – Released from liver when GH-receptor stimulated – Activates somatostatin neurons creating another negative feedback loop 20 Negative Feedback Regulation of GH ❑ GH stimulates IGF-1 secretion from peripheral tissues IGF-1 directly inhibits GH release from somatotrophs in anterior pituitary IGF-1 indirectly inhibits GH secretion by: – Suppressing GHRH secretion from the hypothalamus – Increasing somatostatin secretion from the hypothalamus which then inhibits release of GH from somatotrophs in anterior pituitary GH inhibits its own secretion via the “short loop” feedback by inhibiting anterior pituitary somatotroph secretion of GH 21 Insulin-Like Growth Factor-1 (IGF-1) and Body Size ❑ IGF-1 is primarily responsible for the effects GH has on growth GH stimulates the liver and other tissues to synthesize IGF-1 – – Liver is the major source of circulating IGF-1 which is 90% protein bound Unusual for a peptide hormone IGF-1 can be synthesized and have local effects as a paracrine secretion IGF-1 (from GH) is the most important endocrine regulator of final body size IGF-1 stimulates cell division and cell differentiation – – Stimulates linear growth in long bones By stimulating chondroblasts and osteoblasts in the epiphyseal plate of long bones In bone diameter- many bones 22 Stimulation of Growth by IGF ❑ Stimulation of growth by GH involves two different mechanisms of control: ❑ Primary control is indirect by insulin-like growth factors (IGF) – Peptide hormones stimulate tissue growth by binding to receptors on a variety of plasma membranes – Increases uptake of AAs from ECF to promote protein synthesis – In cartilage and bone- stimulates growth 23 Stimulation of Growth by GH ❑ Direct actions of GH are tissue-specific GH works directly on specific tissues to produce acute metabolic effects that oppose the effects of insulin – aka Diabetogenic/anti-insulin effects – Epithelia and connective tissues GH stimulates cell production – In muscle Reduced glucose uptake – In adipose Promote lipolysis “Glucose-sparing effect of GH” – – GH stimulates lipolysis Tissues use fats instead of glucose If lipolysis excessive- ketosis results – In liver GH stimulates breakdown of glycogen reserves Gluconeogenesis from FA and AA to increase blood glucose 24 Age and GH ❑ GH mobilizes fats stores and increases lean body mass, skeletal and visceral growth ❑ GH secretion peaks during puberty and declines with aging Effects on protein synthesis most apparent in children In adults, GH helps maintain normal blood glucose and to mobilize lipid stores from adipose Not the primary hormone- an adult with GH deficiency can maintain glucose homeostasis if they have normal thyroid, insulin, and glucocorticoid function 25 GH Secretion ❑ Control of GH Secretion – Variable secretion of GH – Most secretion during 1st 2 hours deep sleep- accounts for ~ 70% daily secretion ❑ Physiology factors that increase GH secretion – Hypoglycemia – Increased plasma concentration of AA – Deep Sleep – Acute physical stress (exercise or trauma) – Starvation- especially paired with cellular protein deficiency – GHRH ❑ Factors that decrease GH secretion – Hyperglycemia – Elevated plasma free fatty acids – Aging – Obesity – Exogenous GH – GHIH- somatostatin – IGFs (somatomedins) 26 Abnormalities Related to GH Deficiency ❑ Alterations in GH leads to: Panhypopituitarism – Decreased secretion of all anterior pituitary hormones- (congenital) absence or destruction of anterior pituitary – Can be congenital or occur when tumor destroys pituitary gland Pituitary dwarfism is panhypopituitarism in childhood – Growth stops due at ~ 3 ft – Due to lack of GH secretion before closure of epiphyses in long bones during adolescence – Body regions are proportional – Gonadotropins 1st hormones affected- lack secondary sex characteristics Do not mature sexually to reproduce In Laron dwarfs- GH receptors do not respond to GH African pygmies: do not have ability to synthesize IGF-1 27 Abnormalities Related to GH Excess ❑ Alterations in GH leads to: Gigantism- giants usually 8-9’ tall – Excessive secretion of GH before closure of epiphyses – Due to pituitary tumor of anterior pituitary (somatotrophs) excessive secretion of GH and increased production of IGF-1 causing excessive growth of all body tissues – Usually display hyperglycemia; 10% DM Constant high blood glucose levels cause degeneration of pancreatic  cells Acromegaly – Excessive bone growth and soft tissue growth after adolescence – Cause- anterior pituitary tumor (somatotrophs) that produce and secrete excessive amounts of GH after long bone closure Individual cannot grow in height – Excessive growth is in face, cranium, regions of vertebrae, hands and feet, enlargement in soft tissues of nose and tongue 28 IV. Posterior Pituitary Gland And Its Relation To The Hypothalamus 29 Posterior Pituitary (Neurohypophysis) Produces ADH and OT ❑ Two peptide pre-hormones- neurophysins- are produced in hypothalamic nuclei and processed into – Oxytocin (OT) and antidiuretic hormone (ADH) ❑ ADH formed in the supraoptic nucleus – – – – – – aka Arginine VasopressinPrinciple hormone controlling water balance in the body Concentrates urine and causes water reabsorption Promotes vasoconstriction Secretion controlled by changes in body fluid osmolarity & blood volume The “aggression” hormone ❑ Oxytocin- formed in the paraventricular nucleus – – – – A maternal hormone for parturition, lactation, and natriuretic peptide Inhibits salt appetite Exogenously used to induce uterine contractions and hemorrhage The ”love” hormone- maternal bonding 30 Hypothalamic Nuclei ❑ Most cells express ADH or Oxytocin 2-3% express both hormones Transported with neurophysins (carrier proteins) for transport to axon terminals Pass through infundibulum to posterior pituitary for storage there Both secreted by exocytosis 31 ADH ❑ Mechanism of Secretion Osmoreceptors in the hypothalamus sense changes increased osmolality of blood →osmosis of fluid from osmoreceptors Osmoreceptors send nerve impulses over the hypothalamo-hypophyseal nerve tract to the posterior pituitary Vasopressin- increases fluid retention at kidney & BP→ vasoconstriction – V1 receptors in vascular smooth muscle – V2 receptors mediate ADH effects on kidney Nerve impulses cause Ca+2 influx into nerve endings → exocytosis of ADH and neurophysins into the blood ADH circulates to kidneys, combines with basolateral receptors of the connecting tubule and collecting duct cells ADH stimulates a G-Protein/cAMP 2nd messenger system – Phosphorylation of a protein kinase causes insertion of aquaporins into the luminal membranes – Water is reabsorbed by diffusion from the tubules into vasa recta capillaries 32 Abnormalities of ADH ❑ Deficiency Central Diabetes Insipidus – Lack of ADH – Due to head injuries, surgery, infection, cysts, idiopathic and familial – Symptom: excretion of large volumes of dilute urine (polyuria) – Treat with synthetic ADH via nasal spray ❑ Excess Nephrogenic Diabetes Insipidus: ADH is normal to high – causes: chronic renal disease (chronic pyelonephritis, polycystic kidney) SIADH (syndrome of inappropriate secretion of ADH)- ADH is high – causes: ectopic production of vasopressin * SAH or TBI 33 Physiologic Effects of Oxytocin ❑ Potentiates smooth muscle contraction during labor – Plasma levels are NOT appreciably high before labor – Dilation of cervix sends out nerve impulses (response to Stretch receptors) to the hypothalamus – Nerve cells send Impulses to posterior pituitary for the secretion of oxytocin – Oxytocin stimulates incorporation of gap junctions between uterine smooth muscle cells and increases secretion stimulates milk ejection from the lactating breast Baby nursing stimulates milk ejection and uterine contractions – Given after C-section to improve uterine tone and decrease bleeding 34 1. A 28-year-old woman suffers a traumatic head injury that transects the pituitary stalk. The plasma level of which hormone is expected to increase as a result of this accident? A. ACTH B. FSH C. GH D. LH E. Oxytocin F. Prolactin G. TSH H. Vasopressin 2. A 4-year-old boy is diagnosed with visual disturbances due to a pituitary tumor secreting excess growth hormone. Which of the following disturbances would this boy most likely develop without treatment? A. Acromegaly due to excess GH production B. Acromegaly due to excess IGF-1 production C. Dwarfism due to excess GH D. Dwarfism due to excess IGF-1 production E. Gigantism due directly to excess GH F. Gigantism due to excess IGF-1 production 3. Which statement is true regarding ADH? A. It is synthesized in the posterior pituitary gland B. It increases salt and water reabsorption in the collecting tubules and ducts C. It stimulates thirst D. It has opposite effects on urine and plasma osmolality 4. Which of the following increases secretion of GH? A. Senescence B. IGF-1 C. Somatostatin D. Hypoglycemia E. Exogenous GH administration 5. A 30-year old woman is breastfeeding her infant. During suckling which hormonal response is expected in the woman? A. Increased secretion of ADH from the supraoptic nuclei B. Increased secretion of ADH from the paraventricular nuclei C. Increased secretion of oxytocin from the paravenricular nuclei D. Decreased secretion of neurophysin E. Increased plasma levels of both oxytocin and ADH 35