Physio: Week 8

adrenal medulla

(Nor-) Epinephrine (peptide) >> Heart, blood vessels, liver Stimulates heart rate, blood flow to muscles, and elevation of blood glucose level as part of fight-or-flight response

Outline the general mechanisms underlying the amplification of hormonal signals.

1. a signal from one endocrine gland to the next in a hormonal pathway, and the second set is signal transduction in the target cell. Signals are amplified at each step of the pathway, resulting in a large effect on the target cell or organ. At each step, the hormonal signal is amplified, so that a small amount of corticotropin releasing factor leads to a large effect (in this case, the production of glucose by the liver)

posterior pituitary (know ADH/vasopressin)

Antidiuretic hormone (ADH; vasopressin) (peptide) Kidneys, brain (target) Stimulates uptake of water from the kidneys; involved in pair bonding

adrenal cortex

the outer portion of the adrenal glands Cortisol (steroid)>> Liver, muscles, immune system Regulates response to stress by increasing blood glucose levels and reduces inflammation

▪Diabetes mellitus is a disease characterized by high blood-glucose levels. What two different physiological conditions can produce diabetes? By "physiological mechanisms," it means what processes involved in insulin signaling can be disrupted in ways that will lead to diabetes mellitus?

Diabetes can result either from decreased insulin production by the pancreas (type 1 diabetes) or decreased effect of insulin on target cells (type 2 diabetes). Type 1 diabetes is an autoimmune disease in which the insulin-producing cells in the pancreas are attacked by the immune system. The result is inadequate insulin secretion. Daily injections of insulin can maintain stable normal circulating levels of blood glucose. In individuals with type 2 diabetes, insulin production is unaffected, but cells are not able to respond to normal circulating levels of insulin. Type 2 diabetes is commonly linked to obesity and is most effectively prevented by proper diet and exercise When the control of blood-glucose levels by insulin fails, a disease called diabetes mellitus results. When untreated, diabetic individuals excrete excess glucose in their urine because blood-glucose levels are too high.

▪ Recall how the HPA axis leads to cortisol secretion by the adrenal cortex. We will talk about this stress response in lecture.

During times of stress, such as starvation, fear, or intense physical exertion, ACTH stimulates adrenal cortex cells to secrete cortisol. release of cortisol in response to stress affects a broad range of bodily functions, including blood-glucose levels (Chapter 41), immune function (Chapter 43), and blood pressure

Recall what we mean when we say that a protein is evolutionarily conserved. Appreciate that many hormones and their receptors are highly conserved and that many molecules can function as both hormones and neurotransmitters (e.g., ADH/vasopressin, (nor)epinephrine).

For example, some vertebrate hormones can also be found in many invertebrates. Typically, the same hormone serves different functions in vertebrates and in invertebrates, and may even serve different functions within distinct groups of vertebrates. Thyroid-stimulating hormone (TSH), a hormone released by the anterior pituitary gland that targets the thyroid gland, regulates metabolism in mammals but triggers metamorphosis in amphibians and feather molt in birds. It has even been found in snails and other invertebrates that lack a thyroid gland. Its function in snails appears to be stimulation of the number of sperm or eggs produced antidiuretic hormone, a peptide hormone that regulates water uptake in the kidneys, also functions as a neurotransmitter in the brain influencing mammalian mating and pair-bonding behavior.

Stomach, Small Intestine

Gastrin (peptide)>> Stomach Stimulates protein digestion by secretion of digestive enzymes and acid; stimulates gastric motility -------------------------------------------------- Cholecystokinin (peptide)>> Pancreas, liver, gallbladder Stimulates secretion of digestive enzymes and products from liver and gallbladder Secretin (peptide) >>Pancreas Stimulates bicarbonate secretion from pancreas

Hypothalamus

Hormone: Releaseing factors (peptides) Anterior pituitary gland (target) Stimulate secretion of anterior pituitary hormones

What general features make a chemical compound a hormone, and how do hormones achieve specificity for certain kinds of target cell?

Hormones are chemical compounds that are secreted by a cell or gland that act on other cells in the body either locally or at distant sites (transported in the bloodstream). Hormones achieve specificity by binding to receptors that are present only on their target cells.

▪ Name one physiological process in mammals that involves positive feedback and be thankful that negative feedback kicks in eventually

In response to uterine contractions, the hormone oxytocin is released from the pituitary gland. The release of oxytocin (stimulus) by the pituitary gland causes the uterine muscles (effector) to contract more forcefully. The uterine contractions in turn stimulate (positive feedback) the pituitary gland to secrete more oxytocin, causing the uterine muscles to contract more forcefully and more frequently.

pancreas

Insulin (protein) >>Liver, muscles, fat, other tissues Stimulates uptake of blood glucose and storage as glycogen Glucagon (protein)>> Liver Stimulates breakdown of glycogen and glucose release into blood Somatostatin (peptide) >>Digestive tract Inhibits insulin and glucagon release; decreases digestive activity (secretion, absorption, and motility)

pineal gland

Melatonin (peptide)>> Brain, various organs Regulates circadian rhythms

▪ Define and distinguish between hyperthyroidism and hypothyroidism and list a symptom of each condition. We will talk about scenarios in which thyroid dysfunction is expected to lead to a goiter.

Overproduction of thyroid hormones (hyperthyroidism) creates symptoms that reflect an overly active metabolic state (increased appetite and weight loss), whereas thyroid hormone deficiency (hypothyroidism) creates symptoms that reflect a metabolic state that is too low (fatigue and sluggishness). (neg. feedback important) in cases of iodine insufficiency, the anterior pituitary gland increases its production of TSH because it is no longer receiving negative feedback. Over time, in response to TSH the thyroid gland enlarges to form a goiter, which is observed as an enlargement of the throat. (thyroid hormones T3 and T4 require iodine for their formation)

parathyroid glands

Parathyroid hormone (PTH) (protein)>> Bone Stimulates bone resorption by osteoclasts to increase blood Ca2+ levels

Distinguish between the typical modes of action of peptide and steroid hormones as described in this section and illustrated in Figure 38.8 and in the animation posted on Canvas. Include in your description the typical receptor location, the general mechanism whereby each type of hormone initiates a cellular response, the difference in time scale over which these responses occur, and the reason for this difference in response time

Peptide and amine hormones alter the biochemical activity of the target by initiating signaling cascades within the target cell: The bound receptor activates an enzyme or other molecule within the cell, and it in turn activates another and so on. Typically, the activated enzymes are protein kinases, which phosphorylate other proteins. These signaling cascades can lead to changes in gene expression or they can alter metabolism by turning on or off metabolic enzymes. For example, a peptide or amine hormone could trigger a cell to grow, divide, change shape, or to release another hormone. Peptide and amine hormones act on timescales of minutes to hours. Because steroid hormones are hydrophobic, they diffuse freely across the cell membrane to bind with receptors in the cytoplasm or nucleus, forming a steroid hormone-receptor complex). Hormone-receptor complexes that form in the cytoplasm are transported into the nucleus of the cell. These complexes most commonly act as transcription factors: They stimulate or repress gene expression and thereby alter the proteins produced by the target cell. Consequently, steroid hormones typically have profound and long-lasting effects on the cells and tissues they target, on timescales of days to months. (even slower)

Why do peptide and steroid hormones bind different kinds of receptor, and how does this difference affect the resulting signaling pathways in the target cell?

Peptide hormones bind cell-membrane receptors because they are hydrophilic and cannot diffuse across the cell membrane, activating signaling cascades within the target cell. Steroid hormones diffuse across the cell membrane and bind intracellular cytoplasmic or nuclear receptors, commonly leading to changes in gene expression and protein synthesis within the target cell. -------------------------------------------------------------- Peptide and amine hormones are hydrophilic and bind to cell-membrane receptors activating second messenger pathways, which change the metabolic state or can affect gene expression of the target cell. Steroid hormones are hydrophobic and diffuse into the target cell, where they bind a cytoplasmic or nuclear receptor that allows them to act as transcription factors to alter the gene expression of the cell.

anterior pituitary (know TSH and ACTH)

TSH: Thyroid-stimulating hormone (TSH) (glycoprotein) >>Thyroid gland (target) Stimulates synthesis and secretion of thyroid hormones by the thyroid gland Adrenocorticotropic hormone (ACTH) (peptide) Adrenal glands (target) Stimulates production and release of cortisol

▪ Distinguish between the anterior and posterior pituitary in terms of position, structure, developmental origin, and function (hormones released). Which gland (anterior or posterior pituitary) responds to releasing hormones secreted by the hypothalamus, and which one directly releases hypothalamic hormones into the systemic circulation? Figure 38.11 does a nice job of illustrating these distinctions. Make sure you can identify the portal circulation in the figure. We will talk about the functional significance of this circulatory pattern in lecture.

The anterior pituitary gland forms from epithelial cells that develop and push up from the roof of the mouth, whereas the posterior pituitary gland develops from neural tissue at the base of the brain releasing factors into small blood vessels that travel to and supply the anterior pituitary gland (Fig. 38.11). In response, cells of the anterior pituitary gland release hormones into the bloodstream. These hormones circulate throughout the body and bind to receptors on target cells, tissues, and organs. Instead, the posterior pituitary gland contains the axons of neurosecretory cells whose cell bodies are located in the hypothalamus. These axons release hormones directly into the bloodstream, and these hormones are transported in the blood to distant sites (Fig. 38.11). Consequently, the posterior pituitary is part of the nervous system itself. The hypothalamus communicates with the anterior pituitary gland by secreting releasing factors into the blood. The hypothalamus communicates with the posterior pituitary gland by extending axons of neurosecretory cells into it.

Explain what we mean by the endocrine system and define the term hormone.

The endocrine system is made up of an interacting set of secretory glands and organs, located in different regions of the body, which respond to nervous system signals as well as to blood-borne signals from other organs to regulate internal bodily functions relies on cells and glands that secrete hormones: chemical signals that influence the actions of other cells in the body. Whereas some hormones act locally, many others are released into the bloodstream, allowing them to circulate and influence distant target cells throughout the body

In a sentence or two, describe the role of the hypothalamus in vertebrate endocrine function. You should also be able to identify the position of the hypothalamus and the pituitary gland (which is really two separate glands) in the brain.

The hypothalamus is the main route by which nervous system signals are transmitted to the vertebrate endocrine system. (has neurosecretory cells > neurons bv in brain) The function of the hypothalamus is to transmit these signals to the pituitary gland, the endocrine gland that acts as a control center for many other endocrine glands in the body.

vertebrate endocrine system Know the parts of Figure 38.10 that are relevant given the material you need to know from Table 38.2.

The hypothalamus-pituitary axis. The hypothalamus sends signals to the pituitary gland, which in turn sends signals to diverse cells and organs throughout the body. Anterior pituitary gland: TSH(thyroid), ACTH (adrenal gland), GH (bones/ soft tissue), prolactin Posterior pituitary gland: Oxytocin, ADH (kidney)

Discuss how the nervous system and endocrine system interact and how they differ in their modes of transmission and the time scales over which they act. In one sentence, explain how the two systems contribute to maintaining homeostasis.

The nervous system sends signals rapidly by action potentials running along nerve axons, and communication occurs between adjacent nerve cells by means of neurotransmitters. Whereas some hormones act locally, many others are released into the bloodstream, allowing them to circulate and influence distant target cells throughout the body. As a result, endocrine communication is generally slower and more prolonged than the rapid and brief signals transmitted by nerve cells. The nervous system works closely with the endocrine system to regulate an animal's internal physiological functions- This coordination is accomplished by signals sent from the nervous system to the endocrine system, which distributes chemical signals throughout the body.

▪ In one sentence, describe the function of parathyroid hormone. We will discuss this hormone when we talk about bone in Week 10.

The parathyroid gland secretes parathyroid hormone (PTH). Working together with calcitonin, secreted by the thyroid gland, PTH controls the levels of calcium in the blood (resp. to internal physiological states of the body or to external environmental cues.)

thyroid gland

Thyroid hormones (peptides) >>Many tissues Stimulate and maintain metabolism for development and growth Calcitonin (peptide) Bone (target) Stimulates bone formation by osteoblasts

Parathyroid gland

When circulating levels of calcium fall too low, the parathyroid gland releases PTH, which stimulates osteoclasts to reabsorb bone mineral, halting bone formation and releasing calcium into the bloodstream. When calcium levels are too high, the production of PTH is inhibited and calcitonin is released to shift bone metabolism toward net bone formation, building bone that stores calcium in the skeleton. Note that, as with blood-glucose levels, calcium levels are maintained in a narrow range by negative feedback: The response to the hormone (increasing or decreasing levels of calcium in the blood) is the opposite of the stimulus (low or high levels of calcium in the blood) so that a stable set point is maintained

Thyroid hormones, epinephrine, and norepinephrine

amine hormones (they are derived from tyrosine)

Remember that thyroid hormones

are actually amine hormones, not peptide hormones. Their synthesis requires iodine.

▪ List some negative consequences of chronic stress mediated by elevated cortisol

chronic (long-term) stress often leads to a broad range of unhealthy conditions that include impaired cognitive and immune function, sleep disruption, and fatigue.

Describe how the sympathetic branch of the autonomic nervous system interacts with the adrenal medulla. What hormones does the adrenal medulla release and why does their ability to secrete these hormones make sense in light of the adrenal medulla's developmental origin?

fight-or-flight: The sympathetic nervous system sends axons to the adrenal medulla, the inner part of the adrenal gland. In response to stimulation by the sympathetic nervous system, cells of the adrenal medulla secrete two hormones, epinephrine and norepinephrine. epinephrine and norepinephrine also act as neurotransmitters in the brain. In fact, cells of the adrenal medulla are modified nerve cells that have lost their axons and dendrites.

Describe the hypothalamic-pituitary-adrenal (HPA) axis as a specific example of these amplification mechanisms. You do not need to memorize the numerical values in Figure 38.9 (e.g., 40mg of cortisol), but you should know the other details because this is one pathway we will cover in detail during lecture. Be able to draw a diagram like Figure 38.9 from memory.

from the hypothalamus to the anterior pituitary gland, and then from the anterior pituitary gland to target glands or tissues in the body. The hypothalamus initially releases trace amounts of peptide hormones called releasing factors The releasing factors bind to receptors on cells in the anterior pituitary gland, leading that organ to release a much larger amount of associated hormones. For example, the hypothalamus secretes a corticotropin releasing factor, which stimulates the anterior pituitary gland to release a larger amount of adrenocorticotropic hormone (ACTH) Hormones released by the anterior pituitary gland in turn bind cell receptors in the target organ. In this case, ACTH acts on cells of the adrenal cortex, stimulating their secretion of the hormone cortisol. Cortisol acts on many different cells and tissues in the body, causing what is known as an acute stress response. Among

▪ Know that the pineal gland secretes melatonin and regulates circadian rhythms.

is located in the thalamic region of the brain. In response to darkness, the pineal gland secretes melatonin, a hormone that helps control an animal's state of wakefulness

Explain what we mean by a neurosecretory cell and describe how such cells differ from the typical neurons we discussed earlier in the quarter

neurons that release hormones, which act on endocrine glands or other targets within the insect instead of secreting neurotransmitters that bind to another neuron or to muscle. ex. other neurosecretory brain cells secrete the peptide hormone PTTH, which stimulates the release of ecdysone from the prothoracic gland, triggering the transition from larval to pupal and adult forms.

In one or two sentences, distinguish among the chemical properties of peptide, amine, and steroid hormones (i.e., state the kind of molecule from which each type of hormone is derived and whether each is hydrophobic or hydrophilic). Explain how these distinctions determine where in the cell the receptors for a specific hormone are found

peptide: amino acids (short chains), hydrophilic (ADH, oxytocin) amine: amino acids (aromatic- tyrosine or phenylalanine), hydrophilic steroid: cholesterol derived, hydrophobic (e.g. cortisol) Peptide and amine hormones are more abundant than steroid hormones and are more diverse in their actions. Because most peptide and amine hormones are hydrophilic and cannot diffuse across the plasma membrane (exceptions are thyroid hormones), nearly all these hormones bind to membrane receptors on the surface of the cell

In one sentence explain how hormones circulating in the bloodstream manage to generate responses only in the appropriate target cells.

presence of receptors on cells within target organs that bind specific hormones.

Define homeostasis and review how positive and negative feedback mechanisms function as part of homeostatic reflex pathways In the diagrams shown in Figures 38.4, 38.5, and 38.6, recognize what we have been calling afferent and efferent pathways. Which type of feedback is more commonly involved in such pathways?

the maintenance of a steady physiological state within a cell or an organism, Homeostasis typically depends on negative feedback (blood glucose and ca2+ levels regulated) response: negative feedback on sensor afferent neurons carry nerve impulses from the sensory organs to the central nervous system (integrating center) while the efferent neurons carry nerve impulses from the central nervous system to the muscles. (target or effector)

▪ Define and distinguish between releasing factors and tropic hormones in the hypothalamic-pituitary system.

releasing factors: Some neurosecretory cells in the hypothalamus secrete releasing factors into the bloodstream that cause cells in the anterior pituitary gland to release hormones tropic: control the release of other hormones (anterior pituitary releases) e.g. adrenocorticotropic hormone (ACTH) >> adrenal glands release cortisol, which has diverse effects that include stimulating glucose release into the bloodstream, maintaining blood pressure, and suppressing the immune system.

▪ Know that thyroid hormones bind

to intracellular receptors (unlike most amine and peptide hormones) and increase metabolic rate

The endocrine system helps to regulate an organism's response to its environment. ▪ Draw a general diagram to illustrate how the endocrine system fits into homeostatic reflex pathways of the sort we've been discussing all quarter. Does the endocrine system typically participate in the afferent or efferent part of such a pathway?

triggered by sensory signals received by the nervous system that are relayed to the endocrine system. The endocrine system, with its slower and more prolonged signaling, reinforces physiological changes in the animal's body that better suit the environmental cues received by its nervous system efferent part of the pathway

Know where the pituitary gland (= hypophysis, which you saw in the sheep brain) is found in the mammalian brain and know that it produces growth hormone (among other things...more later).

which is located beneath the brain, makes growth hormone

Recognize scenarios in which you expect negative feedback to operate as part of a homeostatic regulatory mechanism. Be able to draw out a specific pathway based on a description of such a scenario. As you learn the details of endocrine function, you should be able to draw pathways associated with the specific hormones we discuss..

▪ You will have to know the information summarized in Figure 38.5 soon enough, so use this section as an opportunity to memorize the basics of insulin and glucagon signaling in blood glucose regulation. Be able to draw a diagram like Figure 38.5 from memory. After a meal, when blood glucose rises, b (beta) cells of the pancreas secrete the hormone insulin, which circulates in the blood- In response to insulin, muscle and liver cells take up glucose from the blood and either use it or convert it to a storage form called glycogen (Chapter 7). In this way, insulin guards against high levels of glucose in the blood. Alpha cells release glucagon>> breaks down glyc. to glucose and its release from muscle and liver cells. The result is that blood-glucose levels rise. In both cases, the stimulus (either high or low blood-glucose levels) is sensed by cells of the pancreas ( b cells or a cells) and triggers a response (secretion of insulin or of glucagon, bringing blood-glucose levels back to the set point).