47 Endocrine Regulation

Lecture Outline

I. Cells communicate by chemical signals A. Exocrine cells release their secretions into ducts B. Neuroendocrine cells secrete neurohormones and provide a link between the nervous and endocrine systems C. A hormone that acts on the cells that produce it is classified as an autocrine regulator D. Other hormones act on cells both close in proximity and distant, and are known as paracrine regulators 1. Local hormones act as paracrine regulators 2. Local chemical mediators include histamine, growth factors, and nitric oxide E. Prostaglandins are released by most cells of most tissues 1. Many different organs release prostaglandins 2. These hormones act on cells in the immediate vicinity 3. The action of prostaglandins is varied 4. The clinical uses of prostaglandins include induction of labor and the healing of ulcers F. Pheromones are typically not classified as hormones, as they are produced for communication with other animals of the same species G. Hormones can be assigned to four chemical groups 1. Prostaglandins and the juvenile hormones of insects are fatty acid derivatives 2. Steroid hormones are synthesized from cholesterol, and include cortisol, testosterone, estrogens and progestone 3. Amino acid derivatives include amines, which are the simplest hormones a) Amines are synthesized from tyrosine b) Thyroid hormones, epinephrine, and norepinephrine are amines 4. Protein (peptide) hormones include short chains such as oxytocin and ADH and longer chains such as growth hormone, TSH, and neuropeptides

II. Hormone secretion is regulated by negative feedback mechanisms H. Vertebrate endocrine glands constantly secrete at least a small amount of hormone product 1. Hormones are constantly circulating free or bound to plasma proteins 2. Hormones are removed from circulation by target tissues, the liver, and the kidneys I. Negative feedback mechanisms regulate the secretion of most hormones 1. High concentration of a hormone or some other substance inhibits further secretion III. Mechanisms of hormone action J. Hormones combine with specific receptor proteins in target cells 1. Hormones may bind to receptor proteins and thereby affect the metabolism of the target cell 2. Hormones may up-regulate or down-regulate their receptors K. Some hormones enter the cell and activate genes 1. Steroid hormones and amino acid derivatives are small and lipid-soluble, and therefore may pass through the plasma membrane of the target cell 2. The hormones may bind with protein receptors on the nuclear membrane or in the nucleus, leading to the synthesis of RNA coding for particular proteins that cause the ultimate effect of the hormone L. Many hormones bind to cell-surface receptors 1. Hydrophilic hormones (e.g., peptide hormones) cannot cross the plasma membrane, and instead they bind to a specific cell-surface receptor in the plasma membrane 2. Two main types of cell-surface receptors are G-protein linked receptors and enzyme-linked receptors M. Cell signaling through G protein-linked receptors 1. G protein-linked receptors initiate signal transduction, relaying the information from the extracellular hormonal signal to a second messenger in the cytoplasm a) G protein-linked receptors activate G proteins in the plasma membrane b) The activated G protein binds GTP; inactive G protein binds GDP 2. Cyclic AMP is a common second messenger a) The activated G protein activates adenylyl cyclase b) Adenylyl cyclase then catalyzes the conversion of ATP to cAMP c) cAMP activates protein kinases d) Protein kinases catalyze the phosphorylation of a specific protein, which triggers a chain of reactions leading to the particular metabolic effect of the hormone (1) Protein kinases are very specific in action e) cAMP is rapidly inactivated and converted to AMP 3. Phospholipid products and calcium ions can act as second messengers a) Activated G protein may activate phospholipase C, which catalyzes

the conversion of PIP2 into IP3 and DAG b) DAG then activates protein kinase C, which phosphorylates a variety of proteins

c) IP3 opens calcium channels in the ER, releasing calcium ions into the cytoplasm d) Calcium binds calmodulin, and it is in this form that calcium performs functions such as muscle contraction, neural signaling, and enzyme activation N. Enzyme-linked receptors function directly 1. Enzyme-linked receptors are transmembrane proteins that have a hormone binding site on the outside and an enzyme site on the inside of the cell 2. Most of these receptors are receptor tyrosine kinases that bind growth factors 3. Activation of the receptor causes the phosphorylation of a tyrosine amino acid in a specific protein in the cell O. Hormone signals are amplified 1. Signal amplification increases the strength of some hormones

IV. Invertebrate endocrine systems are mainly neuroendocrine P. Invertebrate hormones are primarily secreted by neurons 1. Invertebrate hormones regulate regeneration, molting, metamorphosis, reproduction, and growth Q. Insect development is regulated by hormones 1. An environmental factor, such as temperature, triggers neuroendocrine cells in the brain to release brain hormone (BH, also known as ecdysiotropin) 2. BH is transported down axons and stored in the corpora cardiaca 3. Upon release, BH stimulates the prothoracic glands (true endocrine glands) to release molting hormone (MH or ecdysone) 4. Molting hormone triggers growth and molting 5. Endocrine glands (corpora allata) secrete juvenile hormone, which suppresses metamorphosis during larval growth a) In the absence of juvenile hormone, the pupa forms, molts, and becomes an adult

V. The hypothalamus links the vertebrate nervous and endocrine systems R. Vertebrate hormones regulate growth, development, fluid balance, metabolism, and reproduction S. Homeostasis depends on normal concentrations of hormones 1. Endocrine disorders may involve too little or too much hormone 2. Hypersecretion may cause overstimulation of target cells 3. Hypo secretion may cause understimulation of target cells T. The hypothalamus regulates the pituitary gland 1. The hypothalamus links the nervous and endocrine systems 2. Neurons of the hypothalamus secrete neurohormones, which target the release of hormones by the pituitary gland 3. The pituitary secretes at least 7 distinct hormones that have a wide variety of target cells and effects a) The pituitary of humans consists of an anterior and posterior lobe U. The posterior lobe of the pituitary gland releases hormones produced by the hypothalamus 1. Oxytocin and ADH are peptide hormones released by the posterior lobe 2. These hormones are produced by neurons in the hypothalamus, and travel to the posterior lobe via the axons of the neurons 3. Oxytocin stimulates uterine contractions during labor a) Oxytocin also stimulates contraction of muscle cells in the breast while nursing, resulting in expulsion of milk V. The anterior lobe of the pituitary gland regulates growth and other endocrine glands 1. Tropic hormones stimulate other endocrine glands 2. Releasing hormones and inhibiting hormones produced by the hypothalamus affect the production of hormones produced by the anterior pituitary a) These hormones reach the pituitary by a portal system 3. Growth hormone stimulates protein synthesis a) Growth hormone (GH, also called gonadotropin) stimulates protein synthesis and therefore growth b) GH stimulates liver cells to produce somatomedins, which stimulate skeletal growth at the epiphyseal plates, and general growth of tissues c) GH promotes mobilization of fat and carbohydrate metabolism 4. Growth is affected by many factors a) GH is secreted in pulses during the day in both adults and children b) The hypothalamus secretes GHRH (growth hormone-releasing hormone) and GHIH (growth hormone-inhibiting hormone, also called somatostatin), which signals the pituitary c) Secretion of GH increases during exercise and during sleep d) Emotional support is necessary for production of GH; lack results in psychosocial dwarfism e) Thyroid hormones and sex hormones also interact in the growth process 5. Inappropriate amounts of growth hormone secretion result in abnormal growth a) Pituitary dwarfs are a result of hyposecretion (1) Recombinant GH may now be used to treat this condition b) Gigantism results from juvenile hypersecretion c) Acromegaly results from adult hypersecretion W. Thyroid hormones increase metabolic rate

1. The thyroid produces thyroxine (T4) and triiodothyronine (T3); collectively known as thyroid hormones a) These hormones increase the metabolic rate 2. Thyroid secretion is regulated by negative feedback mechanisms a) When thyroid hormone concentration drops, the pituitary produces TSH, which stimulates the thyroid to produce thyroid hormones b) The hypothalamus is also involved in the loop, as the hypothalamus produces TSH-releasing hormone c) TSH acts by way of cAMP to promote production and release of thyroid hormones 3. Malfunction of the thyroid gland leads to specific disorders a) Juvenile hypothyroidism may lead to cretinism, which is characterized by retarded mental and physical development b) Adult hypothyroidism is characterized by a sluggish metabolic rate c) Extreme adult hypothyroidism causes myxedema, and may be treated by thyroid hormone administration d) Hyperthyroidism increases metabolism, but not growth (1) The most common cause of hyperthyroidism is Grave’s disease, which is an autoimmune disorder e) An enlarged thyroid is a goiter and can be associated with either hypersecretion or hyposecretion (1) Iodine deficiency is a common cause of goiter X. The parathyroid glands regulate calcium concentration 1. The parathyroid glands are embedded in tissue surrounding the thyroid gland 2. Parathyroid hormone (PTH), produced by cells of the parathyroid gland, stimulates calcium release from the bones and calcium reabsorption from the kidney tubules 3. Calcitonin is produced by the thyroid acts in opposition to PTH Y. The islets of the pancreas regulate glucose concentration 1. The islets of Langerhans are the endocrine tissues of the pancreas a) Beta cells secrete insulin and alpha cells secrete glucagon 2. Insulin lowers the concentration of glucose in the blood a) Insulin stimulates cells to take up glucose, to be used immediately or stored as glycogen b) Insulin stimulates the storage of fats and promotes protein synthesis 3. Glucagon raises the concentration of glucose in the blood a) Glucagon acts in opposition to insulin, mobilizing fatty acids, glucose, and amino acids 4. Insulin and glucagon secretion are regulated by glucose concentration in the blood 5. Diabetes mellitus is a serious disorder of carbohydrate metabolism a) Diabetes mellitus is the most common endocrine disorder; serious cases may cause blindness and complications that may lead to death b) Most diabetics have type 2 diabetes (non-insulin dependent diabetics; NIDD) (1) Type 2 diabetics lack functional receptors on target cells (2) This is most common in adults who are overweight, and has a slow onset c) Insulin-dependent diabetes (type 1 diabetes, or IDD) typically develops before age 30, and is due to a decline in the number of beta cells (1) Daily insulin injections may be necessary for correction (2) Type 1 diabetes is an autoimmune disorder d) Diabetes results in hyperglycemia, but the high sugar level falls after kidney clearance of the glucose e) Fat stores are mobilized and may lead to atherosclerosis f) Protein stores are depleted 6. In hypoglycemia the glucose concentration is too low a) Excessive insulin secretion leads to low blood sugar b) Insulin shock may result Z. The adrenal glands help the body cope with stress 1. The paired adrenal glands are located above the kidneys 2. The adrenal medulla initiates an alarm reaction a) The centrally located adrenal medulla is derived from neural tissue and secretes epinephrine and norepinephrine b) These catecholamines are the same as those released by the sympathetic neurons, and the effect is the same c) The effect of hormonal stimulation is much more lengthy than neural stimulation 3. The adrenal cortex helps the body deal with chronic stress a) Cortical hormones are steroids made from cholesterol b) The three classes of cortical hormones include androgens, mineralocorticoids, and glucocorticoids c) Mineralocorticoids include aldosterone, which regulates fluid balance d) Cortisol is the primary glucocorticoid, which stimulates gluconeogenesis as well as mobilization of fats and transportation of amino acids to liver cells e) Stress causes the hypothalamus to secrete corticotropin-releasing factor (CRF), which stimulates the anterior lobe of the pituitary to secrete ACTH f) Hyposecretion of adrenal cortical hormones causes Addison’s disease g) Hyposecretion or continued administration of glucocorticoids causes Cushing’s disease AA. Many other hormones are known 1. The pineal gland produces melatonin 2. Cells of the digestive tract produce hormones 3. The thymus gland produces thymosin 4. Atrial natriuretic factor (ANF) is produced by the heart

Research and Discussion Topics

 It is estimated that there may be 3 million regular anabolic steroid users in the United States. Research the myriad of effects that anabolic steroids have on users. What links to cancers have been shown? What genetically engineered hormones or other substances are now on the "black market" and are being abused in similar ways (such as human growth hormone, HGH)?  Genetically engineered human growth hormone is now being used to treat pituitary dwarfs. Describe its other uses, such as in treatment of burn and AIDS patients.