Introduction to the Endocrine System Hormones 7 Hormones Have Been Known Since Ancient Times What Makes a Chemical a Hormone? Hormones Act by Binding to Receptors Hormone Action Must Be Terminated The Classifi cation of Hormones Most Hormones Are Peptides or Proteins Steroid Hormones Are Derived from Cholesterol Some Hormones Are Derived from Single Amino Acids Control of Hormone Release Hormones Can Be Classifi ed by Their Refl ex Pathways The Endocrine Cell Is the Sensor in the Simplest Endocrine Refl exes Many Endocrine Refl exes Involve the Nervous System Neurohormones Are Secreted into the Blood by Neurons The Pituitary Gland Is Actually Two Fused Glands The Posterior Pituitary Stores and Releases Two Neurohormones The Anterior Pituitary Secretes Six Hormones A Portal System Delivers Hormones from Hypothalamus to Anterior The separation Pituitary of the endocrine Anterior Pituitary Hormones Control Growth, Metabolism, and system into isolated Reproduction subsystems must Feedback Loops Are Diff erent in the Hypothalamic-Pituitary Pathway be recognized as an artifi cial one, Hormone Interactions convenient from In Synergism, the Eff ect of Interacting Hormones Is More Than Additive a pedagogical A Permissive Hormone Allows Another Hormone to Exert Its Full Eff ect point of view but Antagonistic Hormones Have Opposing Eff ects not accurately refl ecting the Endocrine Pathologies interrelated nature Hypersecretion Exaggerates a Hormone’s Eff ects of all these systems. Hyposecretion Diminishes or Eliminates a Hormone’s Eff ects Receptor or Second Messenger Problems Cause Abnormal Tissue — Howard Rasmussen, in Responsiveness Williams’ Textbook of Diagnosis of Endocrine Pathologies Depends on the Complexity of the Endocrinology, 1974 R e fl e x Hormone Evolution Background Basics Focus on . The Pineal Gland Receptors Peptides and proteins Comparison of endocrine and nervous systems Signal transduction Gamma scan of Steroids a goiter of the Specifi city thyroid gland 218 Introduction to the Endocrine System avid was seven years old when the symptoms fi rst ap- growth and development, metabolism, regulation of the inter- peared. His appetite at meals increased, and he always nal environment (temperature, water balance, ions), and repro- seemed to be in the kitchen looking for food. Despite duction. Hormones act on their target cells in one of three basic 7 D eating more, however, he was losing weight. When he started ways: (1) by controlling the rates of enzymatic reactions, (2) by asking for water instead of soft drinks, David’s mother became controlling the transport of ions or molecules across cell mem- concerned, and when he wet the bed three nights in a row, she branes, or (3) by controlling gene expression and the synthesis knew something was wrong. The doctor confirmed the sus- of proteins. pected diagnosis aft er running tests to determine the concentra- tion of glucose in David’s blood and urine. David had diabetes Hormones Have Been Known mellitus. In his case, the disease was due to lack of insulin, a hor- mone produced by the pancreas. David was placed on insulin Since Ancient Times injections, a treatment he would continue for the rest of his life. Although the scientific field of endocrinology is relatively One hundred years ago, David would have died not long af- young, diseases of the endocrine system have been documented ter the onset of symptoms. Th e fi eld of endocrinology, the study for more than a thousand years. Evidence of endocrine abnor- of hormones, was then in its infancy. Most hormones had not malities can even be seen in ancient art. For example, one pre- been discovered, and the functions of known hormones were not Colombian statue of a woman shows a mass on the front of her well understood. Th ere was no treatment for diabetes, no birth neck ( Fig. 7.1 ). Th e mass is an enlarged thyroid gland, or goi- control pill for contraception. Babies born with inadequate se- ter, a common condition high in the Andes, where the dietary cretion of thyroid hormone did not grow or develop normally. iodine needed to make thyroid hormones was lacking. Today, all that has changed. We have identifi ed a long and Th e fi rst association of endocrine structure and function growing list of hormones. The endocrine diseases that once was probably the link between the testes and male sexuality. killed or maimed can now be controlled by synthetic hormones Castration of animals and men was a common practice in both and sophisticated medical procedures. Although physicians do Eastern and Western cultures because it decreased the sex drive not hesitate to use these treatments, we are still learning exactly and rendered males infertile. how hormones act on their target cells. Th is chapter provides an introduction to the basic principles of hormone structure and function. You will learn more about individual hormones as you encounter them in your study of the various systems. Hormones Hormones are chemical messengers secreted into the blood by specialized cells. Hormones are responsible for many func- tions that we think of as long-term, ongoing functions of the body. Processes that fall mostly under hormonal control include RUNNING PROBLEM Graves’ Disease The ball slid by the hole and trickled off the green: another bogey. Ben Crenshaw’s golf game was falling apart. The 33-year-old professional had won the Masters Tournament only a year ago, but now something was not right. He was tired and weak, had been losing weight, and felt hot all the time. He attributed his symptoms to stress, but his family thought otherwise. At their urging, he fi nally saw a physician. The diagnosis? Graves’ disease, which results in an overactive thyroid gland. Fig. 7.1 An endocrine disorder in ancient art. This pre-Colombian stone carving of a woman shows a mass at her neck. This mass is an enlarged thyroid gland, a condition known as goiter. It was consid- ered a sign of beauty among the people who lived high in the Andes mountains. 219 Introduction to the Endocrine System In 1849, A. A. Berthold performed the fi rst classic experi- ment in endocrinology. He removed the testes from roosters CLINICAL FOCUS: DIABETES and observed that the castrated birds had smaller combs, less aggressiveness, and less sex drive than uncastrated roosters. If the testes were surgically placed back into the donor rooster or The Discovery of Insulin into another castrated bird, normal male behavior and comb Diabetes mellitus, the metabolic condition associ- development resumed. Because the reimplanted testes were ated with pathologies of insulin function, has been known not connected to nerves, Berthold concluded that the glands since ancient times. Detailed clinical descriptions of insulin- must be secreting something into the blood that aff ected the defi cient diabetes were available to physicians, but they had entire body. no means of treating the disease. Patients invariably died. Experimental endocrinology did not receive much atten- However, in a series of classic experiments in endocrine physiology, Oscar Minkowski at the University of Strasbourg tion, however, until 1889, when the 72-year-old French physi- (Germany) pinpointed the relationship between diabetes cian Charles Brown-Séquard made a dramatic announcement and the pancreas. In 1889, Minkowski surgically removed of his sexual rejuvenation aft er injecting himself with extracts the pancreas from dogs (pancreatectomy ) and noticed that made from bull testes ground up in water. An international up- they developed symptoms that mimicked those of diabetes. roar followed, and physicians on both sides of the Atlantic began He also found that implanting pieces of pancreas under to inject their patients with extracts of many diff erent endocrine the dogs’ skin would prevent development of diabetes. organs, a practice known as organotherapy . Subsequently, in 1921 Fredrick G. Banting and Charles H. We now know that the increased virility Brown-Séquard Best (Toronto, Canada) identifi ed an antidiabetic substance reported was most likely a placebo eff ect because testosterone in pancreas extracts. Banting and Best and others injected is a hydrophobic steroid that cannot be extracted by an aqueous pancreatic extracts into diabetic animals and found that the preparation. His research opened the door to hormone therapy, extracts reversed the elevated blood glucose levels of diabe- however, and in 1891 organotherapy had its fi rst true success: a tes. From there, it was a relatively short process until, in 1922, purifi ed insulin was used in the fi rst clinical trials. Science woman was treated for low thyroid hormone levels with glycerin had found a treatment for a once-fatal disease. extracts of sheep thyroid glands. As the study of “internal secretions” grew, Berthold’s experiments became a template for endocrine research. Once a gland or structure was suspected of secreting hormones, the classic steps for identifying an endocrine gland became: cells scattered throughout the wall of the stomach or intestine, which has made them diffi cult to identify and isolate. 1 Remove the suspected gland. Th is is equivalent to induc- The Anatomy Summary in Figure 7.2 lists the major ing a state of hormone defi ciency . If the gland does produce hormones of the body and the glands or cells that secrete them, hormones, the animal should start to exhibit anatomical, along with the major eff ects of each hormone. behavioral, or physiological abnormalities. 2 Replace the hormone . This can be done by placing the gland back in the animal or administering an extract of What Makes a Chemical a Hormone? the gland. Th is replacement therapy should eliminate the In 1905, the term hormone was coined from the Greek verb symptoms of hormone defi ciency. meaning “to excite or arouse.” The traditional definition of a 3 Create a state of hormone excess . Take a normal animal hormone is a chemical secreted by a cell or group of cells into and implant an extra gland or administer extract from the the blood for transport to a distant target, where it exerts its gland to see if symptoms characteristic of hormone excess eff ect at very low concentrations.