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contents Principles of Biology 138 Hormones and the Body Hormones are chemical messengers that coordinate functions in the body in response to changes in an animal's internal environment or stimuli from the outside world.

Hormones regulate growth and development. From fertilization through adulthood, hormones mediate growth and development. Hormones even play a role in formation of the bond between mother and child. Picture Partners/Science Source.

Topics Covered in this Module

The Chemical Structure of Hormones Hormones and Homeostasis When Regulation Fails

Major Objectives of this Module

Classify hormones based on their chemical structure and solubility. Describe how hormones trigger responses in target cells. Distinguish between negative and positive feedback loops and give an example of each. Explain the role of hormones in maintaining homeostasis.

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138 Hormones and the Body

Most hormones can be classified based on their chemical composition and structure as either amine hormones, peptide hormones, or steroid hormones. Additionally, hormones can be classified as either water soluble or lipid soluble. The chemical properties and solubility of a hormone have consequences on how it is secreted, how it is transported through the blood, and how it signals to its target cell.

The Chemical Structure of Hormones Hormones are chemical messengers produced in endocrine cells in one part of the body and transported through the blood to target cells in other parts of the body. Hormones carry out numerous regulatory functions in response to stimuli from both outside and inside the body. Hormones also regulate reproduction, growth, and the changes that occur during puberty.

Hormones can be classified based on chemical structure. Hormones are a diverse group of organic compounds with a variety of chemical structures. The major hormones can be classified into three categories — amine hormones, peptide hormones, and steroid hormones. Amine hormones are all derived from single amino acids. Several hormones fall into this category, including thyroxine, , epinephrine, and , which are derived from the amino acid tyrosine, and and , which are derived from the amino acid .

Peptide hormones contain two or more amino acids joined by peptide bonds or are derivatives of such molecules. Some peptide hormones are relatively small molecules; for example, the hormones and are composed of only nine amino acids. Other peptide hormones are much larger; human , for instance, is 191 amino acids in length.

Steroid hormones are derived from cholesterol, a hydrophobic molecule containing four fused rings. Cholesterol is converted into steroid hormones in several endocrine glands, including the adrenal cortex, the testes (in males), and the (in females). Examples of steroid hormones include , , and .

The solubility of a hormone, which is a function of its chemical structure, is important in determining how it is secreted, how it is transported through the body, and how it communicates its message once it reaches its target cell. All peptide hormones and most amine hormones are water soluble. Some amine hormones, including the hormones thyroxine and triiodothyronine, are lipid soluble. Steroid hormones, like their parent compound cholesterol, are lipid soluble.

Water­soluble hormones cannot cross the lipid bilayer of plasma membranes and are typically released from endocrine cells by exocytosis. These hormones diffuse into the bloodstream and travel to target cells, which have cell surface receptors for the hormones associated with the plasma membrane. Hormone binding induces a conformational change in the that activates a pathway, triggering a response in the cell (Figure 1a).

Most lipid­soluble hormones can freely diffuse through the plasma membranes of both the endocrine cell and the target cell. However, the lipid­soluble thyroxine and triiodothyronine must be carried across the plasma membrane by transport proteins. Lipid­soluble hormones travel through the aqueous environment of the blood associated with transport proteins. Some receptors for lipid­soluble hormones are on the cell surface, and others are located inside the cell. To reach intracellular receptors, lipid­soluble hormones diffuse across the plasma membrane. The ­hormone complex moves into the nucleus, where it binds DNA and activates or inhibits expression of particular genes (Figure 1b).

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Figure 1: Transmission pathways of water­soluble and lipid­soluble hormones. Water­soluble hormones (left), which cannot pass through the plasma membrane, bind to a receptor on the outside of the target cell. Signal transduction transfers the signal from the outside of the cell to the inside. Lipid­soluble hormones (right), which can diffuse through cell membranes, often bind intracellular receptors that directly mediate a cellular response. © 2014 Nature Education All rights reserved.

The Integrates Nervous System Input and Endocrine System Output The nervous system senses external stimuli such as the scent of a predator and internal stimuli such as an increase in blood pressure. The endocrine system mediates a response to these stimuli. Thus, these two systems must be closely coordinated. In vertebrates, the hypothalamus, an endocrine gland located in the brain (Figure 1b), is the primary site at which sensory input is converted to endocrine output. The hypothalamus receives sensory input from and sends this information to the pituitary gland, which extends from the bottom of the hypothalamus. The pituitary has anterior and posterior lobes. The is an extension of the hypothalamus that contains axons from specialized neurons originating in the hypothalamus. The specialized neurons, called neurosecretory cells, secrete neurohormones that circulate in the blood and act on distant cells. The neurosecretory cells of the posterior pituitary produce two types of neurohormones: oxytocin and vasopressin (ADH, also known as antidiuretic hormone, or ADP). Vasopressin regulates water and salt balance, and oxytocin moderates behavior and stimulates mammary glands and uterine contractions.

The , which is a separate organ from the posterior pituitary, synthesizes and secretes hormones based on hormonal signals from the hypothalamus. Hormones secreted from the anterior pituitary include growth hormone (GH), thyroid­stimulating hormone (TSH), follicle­stimulating hormone (FSH), (LH), adrenocorticotropic hormone (ACTH), and (PRL). GH stimulates growth and metabolism. TSH stimulates the thyroid gland, which is involved in maintaining metabolic balance. FSH stimulates egg and sperm production. LH regulates ovaries and testes. ACTH causes the adrenal cortex to release glucocorticoids in response to long­term stress. Prolactin stimulates the production and secretion of milk.

The hypothalamus regulates activity of other endocrine glands. For example, in response to stress, the hypothalamus stimulates secretions of the , which sits above the kidneys. The hypothalamus may activate two different stress­response pathways in the adrenal gland, depending on whether the stress is acute or long term. In an acute stress response, which is activated by a scary event such as encountering a tiger in the woods, a nerve signal is sent from the hypothalamus to the adrenal gland. In response, the middle part of the adrenal gland, called the , releases the hormones epinephrine and norepinephrine into the blood. Epinephrine and norepinephrine stimulate the "fight­or­flight" response, which results in the breakdown of glycogen by the and an increase in breathing and rate. Glycogen breakdown frees up glucose, an energy source the body will need for fight or flight; the increased breathing rate enables greater intake of oxygen, which will be needed for the additional cellular respiration cells will be performing during fight or flight to generate energy; and the increased heart rate speeds the delivery of that oxygen to the cells that will be performing cellular respiration.

In long­term stress, which is activated by a stressful event such as loss of a job, the hormone corticotropin­releasing hormone (CRH) is released from the hypothalamus and travels through blood to anterior pituitary. CRH stimulates the anterior pituitary to secrete adrenocorticotropin hormone (ACTH), which travels to the adrenal gland through the bloodstream. In response, the outer part of the adrenal gland, called the adrenal cortex, releases glucocorticoids. Glucocorticoids promote breakdown of fats and proteins to increase blood glucose levels, and reduce immune function. Increased levels of glucocorticoids are associated with improved memory and vigilance, which are presumably needed to get an animal through a stressful situation. However, increased this vigilance takes an emotional toll, and the increased blood sugar necessary to maintain this vigilance takes a physiological toll. Therefore, long­term elevation of glucocorticoid levels is detrimental to health.

IN THIS MODULE

The Chemical Structure of Hormones Hormones and Homeostasis When Hormone Regulation Fails Summary Test Your Knowledge

PRIMARY LITERATURE

Adaptor proteins regulate Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download

SCIENCE ON THE WEB

Overview of Human Hormones Browse this NIH resource of human hormones and their clinical relevance

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138 Hormones and the Body

Hormones and Homeostasis The external environment, as well as availability of food and water, is constantly changing. Despite these changes, physiological conditions, such as metabolic rate, body temperature, and blood solute concentrations, must be maintained within a narrow range. The endocrine system plays a vital role in maintaining constant conditions within the body, or homeostasis, through a process called negative feedback. However, in some cases, a rapid change in internal conditions is necessary. This rapid change is often achieved through positive feedback.

Negative feedback minimizes physiological changes. In negative feedback mechanisms, a change to a physiological system induces responses that reduce the change so that the system returns to the setpoint. An example of a negative feedback mechanism is regulation of body temperature by the hypothalamus. In response to a drop in body temperature, the hypothalamus secretes thyrotropin­releasing hormone (TRH), which causes the anterior pituitary to release thyroid­stimulating hormone (TSH). TSH travels via the bloodstream to the thyroid gland. TSH stimulates thyroid cells to secrete two hormones, thyroxine (T4) and triiodothyronine (T3). T3 and T4 increase metabolic rate in cells throughout the body and and raise the body temperature. T3 is the more biologically active of the two hormones. When body temperature increases, the hypothalamus ceases THR production, and metabolism slows (Figure 2).

Figure 2: Negative feedback regulation of body temperature. Thyroid hormones stimulate metabolism, which raises body temperature. © 2014 Nature Education All rights reserved. Test Yourself

Secretin, a peptide hormone made of 27 amino acids, is produced in the of the small intestine. inhibits gastric acid secretion into the and stimulates bicarbonate secretion into the duodenum (bicarbonate is a base). Describe how pH homeostasis might be accomplished by adjusting secretin secretion levels.

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Positive feedback amplifies an initial physiological change. In positive feedback, a change induces a response that amplifies the change. Positive feedback loops are less common than negative feedback loops because they are associated with instability — they tend to drive a system further away from a homeostatic setpoint. Nevertheless, they are essential in some processes in which a large or rapid response to a stimulus is required. As with negative feedback, positive feedback loops can be mediated by hormones. A classic example of a positive feedback loop is the effect of the hormone oxytocin on uterine contractions during childbirth (Figure 3). Pressure of the fetus's head against the cervix acts initiates a neural signal to the hypothalamus in the brain. In response, the posterior pituitary secretes oxytocin. The oxytocin is carried through the blood to the uterus, where it stimulates contractions of the uterine muscle. In turn, the stronger contractions intensify and prolong the pressure of the fetus's head on the cervix, further stimulating the release of oxytocin until the fetus is born.

Figure 3: Positive feedback loop during labor. The fetus puts pressure on the cervix, which induces the production of oxytocin, which further intensifies uterine contractions. The cycle continues until the fetus is born. © 2014 Nature Education All rights reserved.

In addition to its role in childbirth, oxytocin facilitates other aspects of maternal behavior. For example, it stimulates the release of milk for a nursing child. Increased oxytocin levels present during the postpartum period are believed to be involved in bonding between mother and child.

IN THIS MODULE

The Chemical Structure of Hormones Hormones and Homeostasis When Hormone Regulation Fails Summary Test Your Knowledge

PRIMARY LITERATURE

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download

SCIENCE ON THE WEB

Overview of Human Hormones Browse this NIH resource of human hormones and their clinical relevance

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138 Hormones and the Body

When Hormone Regulation Fails Failures of the endocrine system can disrupt homeostasis, resulting in disease. For example, certain diseases are associated with an imbalance in hormone production by the thyroid gland. One of these diseases is hypothyroidism, a condition in which insufficient thyroid hormone is produced. The two thyroid hormones, T3 and T4, both contain iodine. (T3, or triiodothyronine, contains three iodine atoms, while T4 contains four iodine atoms.) If an iodine deficiency occurs, the body cannot make sufficient thyroid hormones, resulting in hypothyroidism. The hypothalamus senses low levels of circulating thyroid hormone and synthesizes TRH in response. TRH stimulates TSH synthesis in the anterior pituitary. TSH stimulates the growth of thyroid tissue, which results in a swelling in the neck called a goiter. In extreme cases, a goiter can grow to the size of a grapefruit or larger. Hypothyroidism can also result in fatigue, reduced heart rate, and weight gain. Iodine deficiency is particularly dangerous in children because thyroid hormone is essential to normal brain development; hypothyroidism can result in a type of mental retardation historically known as "cretinism." The fortification of table salt with iodine in the modern era has dramatically reduced the incidence of hypothyroidism due to iodine deficiency, especially in the developing world.

Paradoxically, hyperthyroidism, or an overactive thyroid gland, can also result in an enlarged thyroid. An autoimmune condition known as Graves' disease can lead to hyperthyroidism. In Graves' disease, the body inappropriately produces antibodies against the receptor for TSH on thyroid cells. The binding of the antibodies to the receptor mimics the binding of TSH to the receptor, and the thyroid cells secrete T3 and T4 into the blood as a result. The increase in circulating thyroid hormone reduces production of TRH by the hypothalamus and TSH by the anterior pituitary. However, even without TSH, the autoimmune antibodies continue to stimulate the production of thyroid hormone and growth of the thyroid gland as a whole — again resulting in the formation of a goiter. In addition to the goiter, patients with Graves' disease present with exophthalmos (bulging eyes), fatigue, and weight loss with increased appetite. Treatment of Graves' disease includes drugs that interfere with the enzymes that add iodine to thyroid hormones to make them functional. Another treatment involves radioactive iodine, which accumulates in the thyroid and kills some of the thyroid tissue, lowering the amount of thyroid hormone produced to a more normal level. Test Yourself

Both hypothyroidism and hyperthyroidism can result in a goiter. If a patient came to you with a goiter, how could you use a simple blood test to determine which condition she has?

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IN THIS MODULE

The Chemical Structure of Hormones Hormones and Homeostasis When Hormone Regulation Fails Summary Test Your Knowledge

PRIMARY LITERATURE

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download

SCIENCE ON THE WEB

Overview of Human Hormones Browse this NIH resource of human hormones and their clinical relevance

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contents Principles of Biology

138 Hormones and the Body Summary

OBJECTIVE Classify hormones based on their chemical structure and solubility. Most hormones can be classified based on their chemical composition and structure as either amine hormones, peptide hormones, or steroid hormones. Additionally, hormones can be classified as either water soluble or lipid soluble. The chemical properties and solubility of a hormone have consequences on how it is secreted, how it is transported through the blood, and how it signals to its target cell.

OBJECTIVE Describe how hormones trigger responses in target cells. Hormones are produced by endocrine cells and travel through the blood to reach their target cells. Water­soluble hormones are frequently released from endocrine cells by exocytosis. Once in the blood, they diffuse freely to their target cells. At the target cell, they bind to cell surface receptors to transmit their signal. Most lipid­soluble hormones can diffuse through the plasma membranes of both the endocrine cell and the target cell. They require specialized transport proteins to move through the aqueous environment of the blood. At the target cell, they may transmit their signal by interacting with intracellular receptors or by binding to receptors on the cell surface.

OBJECTIVE Distinguish between negative and positive feedback loops and give an example of each. Negative feedback loops produce responses that mitigate the effect of a physiological change. An example of a negative feedback loop is regulation of body temperature by adjustment of thyroid hormone levels. Thyroid hormones stimulate metabolism and increase body heat. Thyroid hormone production increases when body temperature is low and decreases when body temperature is high. Positive feedback loops produce responses that intensify the effect of a physiological change. A positive feedback loop occurs during childbirth. Pressure of the fetus's head on the cervix induces the secretion of the hormone oxytocin, which stimulates uterine contraction, resulting in more pressure on the cervix; the feedback loop continues until the fetus is born.

OBJECTIVE Explain the role of hormones in maintaining homeostasis. Hormones play a significant role in maintaining homeostasis in the human body. Internal stimuli, such as changes in blood glucose or osmolarity, and external stimuli, such as changes in environmental temperature, trigger the release of hormones that allow the individual to produce a response. Disruptions of hormonal regulation can result in disease. For example, hypothyroidism and hyperthyroidism result from failures in the production or regulation of thyroid hormone secretion.

Key Terms

amine hormone A hormone that is chemically derived from an amino acid; examples include epinephrine (derived from tyrosine) and serotonin (derived from tryptophan).

homeostasis Maintenance of a set value for a given physiological parameter.

hormone One of many types of substances produced in a small amount by specialized glands or cells at one site and transported via a circulatory system or other body fluid to target cells at another site in an organism.

hypothalamus An endocrine gland in the brain that integrates neural and endocrine functions.

negative feedback A form of regulation in which a change in some physiological parameter triggers a response that mitigates the change; an important mechanism for maintaining homeostasis.

neurohormone A signaling molecule released from neurons directly into body fluids; mediator of neuroendocrine signaling.

neurosecretory cell A that secretes neurohormones.

peptide hormone A hormone that is composed of multiple amino acids linked by peptide bonds; examples include oxytocin and .

pituitary gland A gland at the base of the hypothalamus; consists of a posterior lobe that secretes neurohormones and an anterior lobe that is an endocrine gland.

positive feedback A form of regulation in which a change in some physiological parameter triggers a response that amplifies, prolongs, or strengthens the change.

receptor A protein to which a signaling molecule binds.

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steroid hormone A hormone that is chemically derived from cholesterol; examples include testosterone, progesterone, and cortisol.

target cell Any cell that has receptors for a specific hormone.

IN THIS MODULE

The Chemical Structure of Hormones Hormones and Homeostasis When Hormone Regulation Fails Summary Test Your Knowledge

PRIMARY LITERATURE

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download

SCIENCE ON THE WEB

Overview of Human Hormones Browse this NIH resource of human hormones and their clinical relevance

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contents Principles of Biology

138 Hormones and the Body

IN THIS MODULE

The Chemical Structure of Hormones Test Your Knowledge Hormones and Homeostasis When Hormone Regulation Fails 1. Based on their chemical structure, most hormones can be classified into which of the following three groups? Summary

amine, peptide, and steroid Test Your Knowledge amine, peptide, and polypeptide hydrophilic, hydrophobic, and lipophilic hydrophilic, lipophilic, and steroid PRIMARY LITERATURE steroid, hydrocarbon, and cyclic Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. 2. Which of the following statements is true about a hormone's solubility? View | Download

Steroid hormones are soluble in water. Peptide hormones cannot diffuse across the plasma membrane. SCIENCE ON THE WEB All amine hormones are water soluble. Overview of Human Hormones None of the statements made in the other choices are correct. Browse this NIH resource of human All of the statements made in the other choices are correct. hormones and their clinical relevance

3. What must a target cell have in order for a hormone to initiate a response?

a cell membrane a second messenger a receptor a nucleus None of the answers are correct.

4. Which of the following statements about homeostasis is true?

A negative feedback loop increases the strength of contractions during childbirth. Positive feedback loops produce responses that mitigate the effect of a physiological change. Positive feedback loops produce responses that intensify the effect of a physiological change. Negative feedback loops produce responses that intensify the effect of a physiological change. Body temperature is regulated by a positive feedback loop.

5. What hormone does the anterior pituitary produce during the stress response?

epinephrine norepinephrine thyroid­stimulating hormone ACTH

6. What stimulus initiates the positive feedback loop that takes place during childbirth?

the release of oxytocin from the adrenal medulla Neural signals from the uterus to the hypothalamus the release of oxytocin from the posterior pituitary pressure of the baby's head against the mother's cervix secretion of milk in the breast tissue

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