Lecture 4: Endocrine System

Transcription

1 Lecture 4: Endocrine System Reading: OpenStax A&P Text Chapter 17 Silverthorn: Chapter 7 There are two different control systems in the human body, responsible for coordinating communication between the body systems. Cells must communicate with each other in order to coordinate actions that maintain homeostasis, because as we ll see, the majority of homeostatic mechanisms involve more than one organ system. Ultimately, the two systems WORK TOGETHER. Comparing Control Systems Target specificity Signal type Speed of signal transmission Speed of effect Duration of effect Control of effect intensity ENDOCRINE SYSTEM General: Any cell with the correct receptor can be affected by a hormone. Hormone: This is a chemical signal Slow: Hormones pass through the blood to reach target and initiate response. Slow: Often hormones initiate protein synthesis in a cell, which takes time. Long: The effect can last a very long time Quantity of hormone NERVOUS SYSTEM Specific: Only cells that synapse with a neuron can be affected. Action potential (AP) and neurotransmitter (NT): AP is electrical, NT is chemical Fast: Some neurons relay information at 120 m/s. This is equal to 268 mph Fast: As soon as NT is released, the effect occurs Instantaneous: Multiple signals can increase the duration Number and speed of AP The Endocrine System A regulatory system that produces hormones. The endocrine system is not truly a distinct system (though it does have specific organs that are identified as endocrine players ) because it plays a role in everything. 1. Hormone: a substance secreted by a gland (or single cell) into the blood that acts on a distant target tissue. A. Hormones can initiate an effect at very low concentrations. You don t need very much hormone to make a big impact. B. They are very specific in their action, because they bind to a certain RECEPTOR on the TARGET CELL (if the cell has no receptor for the hormone, then the cell is not a target cell of that hormone). C. Hormones initiate signal transduction in which chemical reactions are initiated (or halted) within the target cell. 2. Examples of hormone-receptor interactions can (initiate/block) protein synthesis, (activate/inactivate) enzymes, (open/close) ion channels in cell membrane 3. Hormone action is terminated by enzymes that break down the hormone. Then the hormone is degraded, usually in liver or kidney and then excreted in urine or bile 4. There are 3 primary types of hormones: Steroid hormones, peptide hormones, and amino acid derivatives Steroid Hormones Steroids are lipid soluble hormones. What is another word to describe something that is lipid soluble? 1. Steroid hormones are all derived from cholesterol. That means they have a similar structure that is relatively easy to identify. They are produced in the adrenal cortex, gonads, or placenta and often have sterone in the name 2. Mechanism of action A. The are transported in blood, but must be attached to a CARRIER (why???) B. After being released from the carrier, can diffuse into the target cell. (How did you know they could diffuse into the cell?) C. Usually attach to a mobile receptor in nucleus, though some attach to membrane receptors, or floating cytoplasmic receptors D. The hormone-receptor complex then attaches to a specific GENE, and stimulates TRANSCRIPTION of that gene. Resulting mrna travels to the ribosome in the cytoplasm for TRANSLATION, and new proteins are produced. 3. Key Features A. Amount of steroid hormone directly impacts amount of protein produced (and consequent metabolic activity of the cell). There is no amplification possible with steroid hormones B. The mechanism of these molecules is very SLOW. Takes a while to do all these steps between 45min-several days! 30

2 Amino Acid Derivatives 1. Some hormones are derived from single amino acids. Examples: A. Tryptophan is used to produce only melatonin (Note: serotonin is a NT that is also derived from tryptophan) B. Tyrosine is used to produce all other amino acid derivative hormones. 2. There are two categories of tyrosine based hormones: A. Catecholamines (made from 1 tyrosine) are neurohormones that act like peptide hormones i. Epinephrine ii. Norepinephrine (produced in adrenal medulla) iii. Dopamine (produced in hypothalamus also produced in other places in the brain where it acts as a NT) B. Thyroid hormones (made from 2 tyrosines and iodine) i. Produced in thyroid and act like steroid hormones Peptide Hormones If a hormone is not an AA derivative and it is not steroid, then it must be a peptide hormone. 1. Characteristics of peptide hormones A. They are soluble in blood, but many still use carrier proteins so they don t get degraded en route to their target 2. Mechanism of action: second messenger mechanism A. The hormone is first messenger and binds to a receptor on cell membrane B. Receptor changes and activates a cascade of chemical reactions (proteins), with the end product of the cascade being campcyclic adenosine monophosphate C. camp is the second messenger that activates the specific enzyme that produces the cellular response to the hormone. Eventually, camp either diffuses out of the cell (stopping the reaction) OR is deactivated by the cell 3. Key Features A. Because an activated camp keeps working in the cell, the action of a non-steroid hormone can be amplified greatly (small amts of hormone can have BIG effects) B. VERY VERY FAST reaction Hypothalamus 1. Considered the center for homeostasis and controls things like body temp, thirst and urine output, and food intake 2. Autonomic integrating center (impacts smooth muscle, heart and exocrine glands) 3. Produces hormones stored in posterior pituitary (neurohypophysis), including oxytocin and vasopressin (antidiruretic hormone) 4. Produces TROPIC hormones that stimulate the release of hormones produced in the anterior pituitary (adenohypophysis) A. A tropic (or trophic) hormone is one that stimulates the release of another hormone somewhere else. B. These hormones travel through the hypothalamic-hypophyseal portal system (portal system: 2 sets of capillaries connected by larger vessels). Hormone isn t diluted when it travels through the portal system. (There are only 3 portal systems in the body...do you know where they are?) C. Tropic hormones produces in hypothalamus: Prolactin RF(s) (releasing factors), Thyrotropin RH, Corticotropin RH, Growth hormone RH, Somatostatin, Gonadotropin RH Pituitary 1. Considered master gland of body because it secretes more hormones than any other gland. It consists of two parts. A. Anterior (adenohypophysis) is a true endocrine gland that produces 6 hormones: Prolactin, Thyrotropin (TSH), Adrenocorticotropin, Growth hormone (somatotropin), Follicle-stimulating hormone, Leuteinizing hormone. Hypothalamic neurohormones regulate the secretion of these hormones. B. Posterior (nuerohypophysis) is an extension of neural tissue from the hypothalamus. It stores and releases 2 hormones (produced by the hypothalamus): oxytocin and vasopressin (antidiruretic hormone) i. Neuron makes the hormone in the hypothalamus, then transports it down into the post pit where it is STORED. Nervous stimulation causes secretion 31

3 Lab 4: Virtual Rats Activity based on LABORATORY EXERCISE USING VIRTUAL RATS TO TEACH ENDOCRINE PHYSIOLOGY by Cynthia M. Odenweller et al AM. J. PHYSIOL. 273 (ADV. PHYSIOL. EDUC. 18): S24-S40, 1997 Part 1: Setting the stage BACKGROUND AND KEY TERMS RELATED TO THIS EXERCISE The organs of the body communicate with each other through the nervous and endocrine systems. The nervous system uses neurotransmitters and neurons to convey information to and from the brain. In contrast, the endocrine system uses hormones, which are chemical messengers produced by endocrine organs that travel through the bloodstream to exert their effects on distant target organs. In a similar manner, people communicate with each other by using telephones and the postal service. The body s nervous system is analagous to the telephone system because it sends fast, direct messages. The endocrine system is analagous to the postal service because the delivery of the message is slower. Like bulk mail, the message is more diffuse (reaches a greater area) and affects more than one person or organ. Although the hormone travels through the body via the blood, it can only affect those cells with receptors for that specific hormone. Hormones are a slower method of communication, but their effects last longer. The command center for the endocrine system is the hypothalamus, a small, penny-sized portion of the brain. The hypothalamus acts as an endocrine organ that secretes oxytocin and anti-diuretic hormone (ADH, also known as vasopressin). These hormones travel down the infundibulum to the posterior pituitary gland where they are released directly into the bloodstream. The hypothalamus also regulates anterior pituitary gland function through the secretion of releasing hormones, including thyroid-releasing hormone (TRH), corticotropin-releasing hormone (CRH), and gonadotropin-releasing hormone (GnRH). These releasing hormones travel through a specialized blood vessel system (known as the hypothalamic-hypophysial portal system) that connects the hypothalamus to the anterior pituitary gland. From here, they stimulate the synthesis and secretion of anterior pituitary hormones, which include thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), adrenocorticotropin hormone (ACTH), and prolactin. Each of these hormones is released into the bloodstream to affect specific target organs. For example, the hypothalamus secretes TRH, which travels to the pituitary gland to release TSH; TSH travels to the thyroid gland (the target organ) and stimulates the release of thyroid hormone. It is important to note that the hypothalamic releasing hormones are only required for the synthesis and release of the anterior pituitary hormones. The posterior pituitary hormones are synthesized by the hypothalamus and travel down neurons to be released from the posterior pituitary gland. Because the anterior pituitary gland secretes multiple hormones, it is frequently referred to as the master gland. For this experiment, we will focus on the hypothalamus only as a regulator of the anterior pituitary gland. Figure 1 shows the relationship between the hypothalamus and the pituitary gland. Figure 1: Secretion of hypothalamic hormones. Hypothalamic releasing hormones travel down the hypothalamic- hypophysial portal system to the anterior pituitary gland, where they stimulate the synthesis and release of anterior pituitary hormones [adrenocorticotropin hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and prolactin]. In contrast, the posterior pituitary gland does not require releasing hormones, because the hypothalamus synthesizes and secretes both anti-diuretic hormone (ADH) and oxytocin. 32

4 In the endocrine system, negative feedback is used to inhibit further hormone secretion. When a sufficient amount of hormone has been released, it communicates or feeds back to suppress the releasing organ. In other words, the gland has released enough hormone to fulfill its function; this is sensed by the body, and production of the hormone ceases. Negative feedback not only inhibits the releasing organ, but can also inhibit the pituitary gland and/or hypothalamus. By using a negative feedback system, the body produces only the amount of hormone it needs without wasting its resources. Conversely, in positive feedback, the end product further stimulates the releasing organ. This form of feedback is less common and tends to disrupt homeostasis. Answer the following questions 1. Describe the relationship between the hypothalamus and the anterior pituitary gland. 2. List the hormones released by the anterior pituitary gland. 3. Why is the anterior pituitary called the master gland? 4. What is negative feedback? Part 2: Today s Hormones The pathways of three hormones are examined in this experiment: thyroid hormone, cortisol, and testosterone. The hormonal pathways are similar in all three cases. It is important to realize that the hypothalamus secretes a releasing hormone to regulate each of the hormones secreted from the anterior pituitary gland. In this way, the hypothalamus is like a command center. If the hypothalamus is not stimulated, the hypothalamic releasing hormones (TRH, CRH, and GnRH) will not stimulate the anterior pituitary gland to secrete its hormones. Thyroid hormone The hypothalamus releases TRH, which travels to the anterior pituitary gland via the bloodstream to stimulate production of TSH. TSH travels to the thyroid gland (located by the trachea) to stimulate the production and release of thyroid hormone. Thyroid hormone influences the growth rate of many body tissues and is necessary for proper central nervous system development. Its main function is to increase a person s basal metabolic rate (BMR) and to increase heat production. An excess of thyroid hormone can negatively feed back to inhibit further thyroid hormone release from the thyroid gland, TSH secretion from the anterior pituitary gland, and/or TRH release from the hypothalamus. Cortisol The hypothalamus releases CRH, which travels to the anterior pituitary gland and stimulates the release of ACTH. ACTH stimulates the adrenal glands (located on top of the kidneys) to secrete cortisol, which promotes the breakdown of proteins and fats and helps the body adapt to stress. Cortisol functions to provide the body with fuel by breaking down the materials of the body. This is a catabolic process. Under normal conditions, excess cortisol in the bloodstream will negatively feed back to the hypothalamus (to inhibit CRH release), anterior pituitary gland (to inhibit ACTH secretion), and/or to the adrenal gland (to inhibit further cortisol release). The release of CRH is regulated by negative feedback, circadian rhythms, and stress. Cortisol can also act as an immunosuppressive and anti-inflammatory agent. If cortisol is administered in large doses, its immunosuppressive properties will cause the organs of the immune system to shrink. In this experiment, the thymus gland will represent the organs of the immune system. Testosterone The hypothalamus releases GnRH, which travels to the anterior pituitary gland and stimulates the release of LH. LH is seen in both males and females but has different functions. In the male, LH travels to the Leydig cells (aka interstitial cells) that are located in the connective tissue between the seminiferous tubules of the testes. The Leydig cells release testosterone, which is responsible for the male sex drive and secondary sex characteristics, such as increased body hair and a deeper voice. An excess of testosterone can cause an increase in muscle mass, which is an anabolic process. Figure 3 presents the relative anatomy of the male reproductive tract. The pathways of all three hormones can be understood by looking at a visual representation in Fig Figure 3: Organs of the male reproductive tract

5 Figure 4: Negative feedback control (hormone pathways). GnRH, gonadotropin-releasing hormone. The glands and tissues of our body enlarge (increase in size) if they are continuously activated; this is called hypertrophy. For example, a person who lifts weights will continually stimulate the activated muscles, resulting in hypertrophy. This can be easily observed when comparing a bodybuilder to an average person; the bodybuilder s muscles appear larger in comparison. In contrast, if a gland or tissue is continuously inhibited it will shrink in size or atrophy. For example, if a cast is placed on a person s arm for 6 weeks and then removed, a drastic reduction in muscle mass can be seen. The cast prevented any movement (stimulation) of the limb, allowing atrophy to occur. There are many diseases that may result from a deficiency or excess of hormones. These hormonal imbalances may lead to changes in organ or gland size (hypertrophy or atrophy). For example, hyperthyroidism is the excessive production of thyroid hormone. The most common cause of hyperthyroidism is Grave s disease; the symptoms include increased BMR, a constant feeling of warmth, nervousness, and an enlarged thyroid gland (known as goiter). In contrast, hypothyroidism is the result of decreased levels of thyroid hormone. A patient with hypothyroidism will present symptoms of low BMR, a decreased appetite, abnormal CNS development, and an intolerance to cold. Cushing s syndrome is the result of excess secretion of cortisol (hypercortisolism). They symptoms of Cushing s syndrome include personality changes, hypertension, osteoporosis, and weight loss. If an excess level of cortisol remains in the body, protein degradation will occur, leanding to a wasting effect. Hyposecretion of cortisol is characterized by symptoms such as defective metabolism, mental confusion, and decreased ability to adapt to stress. Decreased amounts of testosterone in the body primarily affect the sexual organs. If testosterone levels are low, males will not develop normally and will have sperm counts too low to fertilize an egg. The condition of excess testosterone is rare, but causes premature sexual development. Answer the following questions 5. Describe the effects of thyroid hormone. 6. Describe the effects of cortisol. 7. Describe the role of LH in males. 8. What is the difference between hypertrophy and atrophy? 9. Consider the differences between hyperthyroidism and hypothyroidism. What are some characteristics of each? 10. What are the effects of decreasing testosterone? 34

6 Part 3: Make a hypothesis This exercise is designed to determine the identity of an unknown hormone by observing the effect it (the hormone) had on the organs of the male rat. The exercise is a modification of an experiment from a laboratory manual that is currently in press (1). Before beginning this activity, use the text in this handout to fill in Table 1. Table 1: Compile all your new knowledge in one place. This information will be helpful for filling in Table 2. Hormone: TRH TSH ACTH Cortsol Testosterone LH PRODUCED BY: ACTS ON: Table 1 will help you fill in Table 2, which requires you to estimate the impact you think certain hormones will have on the size of target organs. If you think the hormone will cause an organ to increase in size, put a + in the box. If you think a hormone will cause an organ to decrease in size, put a -- in the box. If the hormone does not target the organ, you can leave the box blank. Table 2: Comparison of hormonal effects on different organs. To fill in this chart, ask yourself, If I increased the amount of THIS hormone (at the top of the column), how would it affect the size of THIS organ (on the left side of the row)? How does increasing this hormone affect the: Pituitary gland TRH TSH ACTH Cortsol Testosterone LH Intact Castrate Intact Castrate Thyroid gland Adrenal gland Thymus gland Testes Prostate Seminal vesicles Body weight Part 4: Analyze Your Rat Pack Acquire a Rat Pack from your instructor, which includes data from seven sets of male laboratory rats, two rats per set. One set is the control group and the remaining six are experimental groups. The rats are all male to simplify the study of the relationship between the reproductive and endocrine systems. In each set of rats there is an intact rat and a castrate rat. The castration involved removal of the testes to eliminate testosterone production. The two rats (normal and castrate) of each group were treated alike in all other ways (food, water, etc.). All rats, except for those in the control group were injected with a hormone on a daily basis for 2 weeks. Autopsies were performed on the animals at the end of that time. 35 Figure 6: Graphic representation of organs studied in the autopsy.

7 The students who performed this experiment were very disorganized and rushed through the work, making errors in labeling the bottles of hormone. They obtained the following results for organ weights after the autopsies were performed. In just two weeks, the students noted amazing changes in the size of certain organs when they compared the experimental group of rats with the control group. Using the information in this lab, match the unknown rat groups with their respective hormones. The bottles of unlabeled hormones included ACTH, cortisol, LH, TSH, TRH, and testosterone. To help in determining the identity of the unknown hormones, look for changes between the control values and the values after treatment with the unknown hormone (both the intact and castrate animal). The changes between the control rats and the rats that were treated with the unknown hormone should be greater than 20% if they are to be considered significantly different. If the change is less than 20%, it is attributed to experimental or biological error. Experimental errors may include small errors in calibration procedures, measurements, or instrumentation. Other variability can be due to differences between animals and is considered biological error. Determining statistical significance. Fill in Table 3 to determine the RANGE of statistically significant masses (in milligrams) for each organ. This is the range that includes NORMAL VARIATION. Begin by recording the values for the intact control rat. Multiply this number by 0.20 to find 20% of the value. Then ADD 20% to the original weight to determine the upper limit of the normal range, and SUBTRACT 20% of the original weight to determine the lower limit of the normal range. Repeat for the castrate rat. Table 3: The range of statistically significant variation in organ mass (in milligrams) based on 20% of control organ mass. Control Intact Mass (mg) x 0.20 Upper limit Lower limit Pituitary gland Thyroid Adrenal Thymus Testes - Control Castrate Mass (mg) x 0.20 Upper limit - Pituitary Thyroid Adrenal Thymus Testes - Lower limit Prostate - Seminal vesicles - Body weight - Prostate - Seminal vesicles - Body weight - Now you need to compare each rat to the data in the previous table to determine whether or not the rat displays statistically significant differences from the control. For each INTACT rat, list the organs that show statistically significant differences from the control. Intact: Rat 1 Rat 2 Rat 3 Rat 4 Rat 5 Rat 6 List of organs that show statistically significant differences from the control Repeat the previous process for all the castrate rats. Castrate: Rat 1 Rat 2 Rat 3 Rat 4 Rat 5 Rat 6 List of organs that show statistically significant differences from the control 36

8 Part IV: Final Analysis Use the data from your tables to figure out the identity of each hormone (1-6). Compare your results to other groups to check your understanding. 11. What was hormone 1? How did you know? What evidence supports your conclusion? Explain. 12. What was hormone 2? How did you know? What evidence supports your conclusion? Explain. 13. What was hormone 3? How did you know? What evidence supports your conclusion? Explain. 14. What was hormone 4? How did you know? What evidence supports your conclusion? Explain. 15. What was hormone 5? How did you know? What evidence supports your conclusion? Explain. 16. What was hormone 6? How did you know? What evidence supports your conclusion? Explain. 37

9 External Brain 4: Endocrine System Study Guide 1. Compare and contrast the endocrine system and the nervous system. 2. Define and describe the word HORMONE. 3. Compare and contrast the three different types of hormones. 4. Briefly compare and contrast catecholamines and thyroid hormones. 5. Clearly describe the general mechanism of action for a peptide (protein) hormone. 6. Clearly describe the general mechanism of action for a steroid hormone 7. Describe the anatomical relationship between the hypothalamus and the pituitary. (How are they related structurally? How are they connected?) 8. Describe the anatomy of the pituitary gland. 9. What is a tropic (trophic) hormone? Be able to identify whether or not a hormone is considered tropic. 10. What is a portal system? 11. Describe the hypothalamic-hypophoseal portal system. What is the advantage of having a portal system in this location? 12. Given a hormone-treated rat, be able to determine which hormone it was most likely treated with. Include information in your EB so you can answer questions like this WITHOUT your lab handout. 38