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Pancreas Copyright 2009, John Wiley & Sons, Inc. Pancreatic Islets Both exocrine and endocrine gland Roughly 99% of cells produce digestive enzymes Pancreatic islets or islets of Langerhans Alpha or A cells secrete glucagon – raises blood sugar Beta or B cells secrete insulin – lowers blood sugar Delta or D cells secrete somatostatin – inhibits both insulin and glucagon F cells secrete pancreatic polypeptide – inhibits somatostatin, gallbladder contraction, and secretion of pancreatic digestive enzymes Copyright 2009, John Wiley & Sons, Inc. Cell Types in the Pancreatic Islets Alpha cells (20%) produce glucagon Beta cells (70%) produce insulin Delta cells (5%) produce somatostatin F cells produce pancreatic polypeptide 18-3 1 Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 2 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) 3 Glucose released by hepatocytes raises blood glucose level to normal 5 High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN 6 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis 7 Blood glucose level falls 4 If blood glucose continues to rise, hyperglycemia inhibits release of glucagon 8 If blood glucose continues to fall, hypoglycemia inhibits release of insulin Pineal Gland Copyright 2009, John Wiley & Sons, Inc. Pineal Gland Attached to roof of 3rd ventricle of brain at midline Masses of neuroglia and pinealocytes Melatonin – amine hormone derived from serotonin Appears to contribute to setting biological clock More melatonin liberated during darkness than light Copyright 2009, John Wiley & Sons, Inc. SCN and sleep Wild type animal with period of ~24h Tau mutant with period of ~20h A SCN lesioning B Transplanting SCN of donor with ~20-h period C SCN lesioning abolishes circadian rhythm Wild type animal acquires period of donor (~20h) Modified from Ralph and Lehman, Trends Neuro 1991 Melatonin: Produced by pineal gland, released at night-inhibited during the day (circadian regulation); initiates and maintain sleep; treat symptoms of jet lag and insomnia Hypothalamus and Pituitary Gland Anterior pituitary Release of hormones stimulated by releasing and inhibiting hormones 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 called tropic hormones Copyright 2009, John Wiley & Sons, Inc. Hormones of the Anterior Pituitary 1. Human growth hormone (hGH) or somatotropin Stimulates secretion of insulin-like growth factors (IGFs) that promote growth, protein synthesis 2. Thyroid-stimulating hormone (TSH) or thyrotropin Stimulates synthesis and secretion of thyroid hormones by thyroid 3. Follicle-stimulating hormone (FSH) Ovaries initiates development of oocytes, testes stimulates testosterone production 4. Luteinizing hormone (LH) Ovaries stimulates ovulation, testes stimulates testosterone production Copyright 2009, John Wiley & Sons, Inc. Hormones of the Anterior Pituitary 5. Prolactin (PRL) Promotes milk secretion by mammary glands 6. Adrenocorticotropic hormone (ACTH) or corticotropin Stimulates glucocorticoid secretion by adrenal cortex 7. Melanocyte-stimulating Hormone (MSH) Copyright 2009, John Wiley & Sons, Inc. Function of Anterior Pituitary Hormones Copyright 2009, John Wiley & Sons, Inc. 1) Human Growth Hormone Increases synthesis of insulin-like growth factors “(IGFs) or somatomedins” at target cells target cells are liver, skeletal muscle, cartilage and bone. IGF will work locally or enter bloodstream and they will lead to: increases cell growth & cell division Increases cell uptake of amino acids & synthesis of proteins stimulate lipolysis in adipose so fatty acids used for ATP retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain 18-15 Regulation of hGH Low blood sugar stimulates release of GNRH from hypothalamus anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells High blood sugar stimulates release of GHIH from hypothalamus 18-16 less hGH from anterior pituitary, glycogen does not breakdown into glucose Diabetogenic Effect of Human Growth Hormone Excess of growth hormone raises blood glucose concentration pancreas releases insulin continually beta-cell burnout Diabetogenic effect causes diabetes mellitis 18-17 2) Thyroid Stimulating Hormone (TSH) Hypothalamus regulates the production of Thyroid Stimulating Hormone (TSH) TSH stimulates the synthesis & secretion of T3 and T4 at thyroid gland Metabolic rate stimulated 18-18 3) Follicle Stimulating Hormone (FSH) FSH functions initiates the formation of follicles within the ovary stimulates follicle cells to secrete estrogen stimulates sperm production in testes 18-19 4) Luteinizing Hormone (LH) In females, LH stimulates secretion of estrogen(with FSH) ovulation of secondary oocyte from ovary formation of corpus luteum secretion of progesterone In males, stimulates interstitial cells to secrete testosterone 18-20 5) Prolactin (PRL) Under right conditions, prolactin causes milk production Suckling reduces cause prolactin levels rise along with milk production Nursing ceases & milk production slows 6) Adrenocorticotrophic Hormone ACTH stimulates cells of the adrenal cortex that produce glucocorticoids 18-22 7) Melanocyte-Stimulating Hormone Releasing hormone from hypothalamus increases its release From the anterior pituitary Function not certain in humans (increase skin pigmentation in frogs ) 18-23 Regulation of Ant. Pitutary Hormone Secretion negative feedback Hypothalamus Copyright 2009, John Wiley & Sons, Inc. Hypothalamus Hypothalamus is a section of brain above where pituitary gland is suspended from by infundibulum or stalk Functions of hypothalamus • Endocrine function • Sleep • Caloric balance • Affective behavior • Osmolarity balance • Memory • Thermal regulation • Somatic movements • Autonomic balance Hypothalamus Hypothalamus is a section of brain above where pituitary gland is suspended from by infundibulum or stalk Hypothalamus is a major link between nervous and endocrine system It receives input from cortex, thalamus, limbic system & internal organs Is influenced by emotions and the metabolic state of the individual Copyright 2009, John Wiley & Sons, Inc. Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence Hypothalamus controls pituitary gland with 7 different releasing & inhibiting hormones Hypothalamus and anterior pituitary Flow of Blood to Anterior Pituitary Controlling hormones enter blood Travel through portal veins Enter anterior pituitary at capillaries 18-33 Hypothalamic control of anterior pituitary secretions Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence Hypothalamus controls pituitary gland with 7 different releasing & inhibiting hormones Endocrine Control: Three Levels of Integration Figure 7-13: Hormones of the hypothalamic-anterior pituitary pathway Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence Hypothalamus controls pituitary gland with 7 different releasing & inhibiting hormones Hypothalamic control of anterior pituitary Hormones Effect on Ant Pituitary 1. Thyrotropin-releasing hormone (TRH) (+) TSH & Prolactin 2. Corticotropin-releasing hormone (CRH) (+) ACTH 3. Growth hormone releasing hormone (GHRH) (+) GH 4. Prolactin releasing hormone (PRH) (+) Prolactin 5. Gonadotropin-releasing hormone (GnRH) (+) Gonadotropic hormones (LH, & FSH) 6. Prolactin inhibitory hormone (PIH) “Dopamine” (-) Prolactin 7. Growth hormone inhibitory hormone (GHIH) “Somatostatin (SS)” (-) GH (-) TSH Hypothalamic hormones Hypothalamus GnRH + FSH & LH GHRH + GHIH/SS GH - + TSH PRIH TRH + PRH + Prolactin Anterior Pituitary Copyright 2009, John Wiley & Sons, Inc. CRH + ACTH Regulation of Ant. Pitutary Hormone Secretion negative feedback Hypothalamus Copyright 2009, John Wiley & Sons, Inc. Negative Feedback Regulation Copyright 2009, John Wiley & Sons, Inc. 1 Low blood glucose (hypoglycemia) stimulates release of GHRH 6 High blood glucose (hyperglycemia) stimulates release of GHIH 7 GHIH inhibits secretion of hGH by somatotrophs 2 GHRH stimulates secretion of hGH by somatotrophs hGH Anterior pituitary 3 hGH and IGFs speed 8 A low level of hGH and up breakdown of liver IGFs decreases the rate glycogen into glucose, of glycogen breakdown which enters the blood in the liver and glucose more rapidly enters the blood more slowly 4 Blood glucose level rises to normal (about 90 mg/100 mL) 9 Blood glucose level falls to normal (about 90 mg/100 mL) 5 If blood glucose 10 If blood glucose continues to increase, continues to decrease, hyperglycemia inhibits hypoglycemia inhibits release of GHRH release of GHIH