what second messenger most directly causes calcium ions to be released from intracellular stores?

The Endocrine Organization

Hormones

Learning Objectives

By the terminate of this department, you will be able to:

Identify the three major classes of hormones on the footing of chemical structure
Compare and contrast intracellular and cell membrane hormone receptors
Describe signaling pathways that involve camp and IP3
Identify several factors that influence a target cell's response
Discuss the office of feedback loops and humoral, hormonal, and neural stimuli in hormone command

Although a given hormone may travel throughout the body in the bloodstream, it volition affect the activeness only of its target cells; that is, cells with receptors for that particular hormone. One time the hormone binds to the receptor, a chain of events is initiated that leads to the target jail cell's response. Hormones play a critical role in the regulation of physiological processes because of the target cell responses they regulate. These responses contribute to human reproduction, growth and development of body tissues, metabolism, fluid, and electrolyte balance, sleep, and many other body functions. The major hormones of the human being body and their furnishings are identified in (Figure).

Endocrine Glands and Their Major Hormones
Endocrine gland	Associated hormones	Chemic form	Effect
Pituitary (anterior)	Growth hormone (GH)	Protein	Promotes growth of torso tissues
Pituitary (anterior)	Prolactin (PRL)	Peptide	Promotes milk product
Pituitary (anterior)	Thyroid-stimulating hormone (TSH)	Glycoprotein	Stimulates thyroid hormone release
Pituitary (anterior)	Adrenocorticotropic hormone (ACTH)	Peptide	Stimulates hormone release by adrenal cortex
Pituitary (anterior)	Follicle-stimulating hormone (FSH)	Glycoprotein	Stimulates gamete production
Pituitary (inductive)	Luteinizing hormone (LH)	Glycoprotein	Stimulates androgen production by gonads
Pituitary (posterior)	Antidiuretic hormone (ADH)	Peptide	Stimulates water reabsorption past kidneys
Pituitary (posterior)	Oxytocin	Peptide	Stimulates uterine contractions during childbirth
Thyroid	Thyroxine (T₄), triiodothyronine (T_iii)	Amine	Stimulate basal metabolic charge per unit
Thyroid	Calcitonin	Peptide	Reduces claret Ca²⁺ levels
Parathyroid	Parathyroid hormone (PTH)	Peptide	Increases blood Caⁱⁱ⁺levels
Adrenal (cortex)	Aldosterone	Steroid	Increases blood Na⁺ levels
Adrenal (cortex)	Cortisol, corticosterone, cortisone	Steroid	Increment claret glucose levels
Adrenal (medulla)	Epinephrine, norepinephrine	Amine	Stimulate fight-or-flight response
Pineal	Melatonin	Amine	Regulates slumber cycles
Pancreas	Insulin	Protein	Reduces blood glucose levels
Pancreas	Glucagon	Protein	Increases blood glucose levels
Testes	Testosterone	Steroid	Stimulates development of male secondary sex characteristics and sperm production
Ovaries	Estrogens and progesterone	Steroid	Stimulate development of female secondary sex characteristics and prepare the trunk for childbirth

Types of Hormones

The hormones of the human trunk tin exist divided into two major groups on the basis of their chemical structure. Hormones derived from amino acids include amines, peptides, and proteins. Those derived from lipids include steroids ((Figure)). These chemical groups affect a hormone's distribution, the type of receptors information technology binds to, and other aspects of its function.

Amine, Peptide, Poly peptide, and Steroid Hormone Structure

Amine Hormones

Hormones derived from the modification of amino acids are referred to as amine hormones. Typically, the original structure of the amino acid is modified such that a –COOH, or carboxyl, group is removed, whereas the [latex]-{\text{NH}}_{three}^{+}[/latex], or amine, group remains.

Amine hormones are synthesized from the amino acids tryptophan or tyrosine. An example of a hormone derived from tryptophan is melatonin, which is secreted by the pineal gland and helps regulate circadian rhythm. Tyrosine derivatives include the metabolism-regulating thyroid hormones, too as the catecholamines, such every bit epinephrine, norepinephrine, and dopamine. Epinephrine and norepinephrine are secreted by the adrenal medulla and play a role in the fight-or-flight response, whereas dopamine is secreted by the hypothalamus and inhibits the release of certain anterior pituitary hormones.

Peptide and Protein Hormones

Whereas the amine hormones are derived from a unmarried amino acid, peptide and poly peptide hormones consist of multiple amino acids that link to form an amino acid chain. Peptide hormones consist of short bondage of amino acids, whereas protein hormones are longer polypeptides. Both types are synthesized like other torso proteins: DNA is transcribed into mRNA, which is translated into an amino acid chain.

Examples of peptide hormones include antidiuretic hormone (ADH), a pituitary hormone important in fluid balance, and atrial-natriuretic peptide, which is produced by the centre and helps to decrease blood pressure. Some examples of poly peptide hormones include growth hormone, which is produced by the pituitary gland, and follicle-stimulating hormone (FSH), which has an fastened saccharide group and is thus classified as a glycoprotein. FSH helps stimulate the maturation of eggs in the ovaries and sperm in the testes.

Steroid Hormones

The primary hormones derived from lipids are steroids. Steroid hormones are derived from the lipid cholesterol. For example, the reproductive hormones testosterone and the estrogens—which are produced by the gonads (testes and ovaries)—are steroid hormones. The adrenal glands produce the steroid hormone aldosterone, which is involved in osmoregulation, and cortisol, which plays a office in metabolism.

Like cholesterol, steroid hormones are non soluble in water (they are hydrophobic). Because blood is water-based, lipid-derived hormones must travel to their target cell bound to a ship poly peptide. This more complex construction extends the half-life of steroid hormones much longer than that of hormones derived from amino acids. A hormone's half-life is the time required for one-half the concentration of the hormone to be degraded. For example, the lipid-derived hormone cortisol has a half-life of approximately 60 to ninety minutes. In contrast, the amino acid–derived hormone epinephrine has a half-life of approximately ane minute.

Pathways of Hormone Action

The message a hormone sends is received by a hormone receptor, a protein located either inside the cell or within the prison cell membrane. The receptor will process the message past initiating other signaling events or cellular mechanisms that result in the target prison cell's response. Hormone receptors recognize molecules with specific shapes and side groups, and respond only to those hormones that are recognized. The aforementioned type of receptor may be located on cells in different body tissues, and trigger somewhat different responses. Thus, the response triggered by a hormone depends not only on the hormone, but as well on the target cell.

In one case the target prison cell receives the hormone signal, information technology can respond in a diverseness of ways. The response may include the stimulation of protein synthesis, activation or deactivation of enzymes, alteration in the permeability of the jail cell membrane, altered rates of mitosis and cell growth, and stimulation of the secretion of products. Moreover, a unmarried hormone may be capable of inducing different responses in a given cell.

Pathways Involving Intracellular Hormone Receptors

Intracellular hormone receptors are located within the cell. Hormones that bind to this type of receptor must be able to cross the cell membrane. Steroid hormones are derived from cholesterol and therefore tin readily diffuse through the lipid bilayer of the cell membrane to reach the intracellular receptor ((Effigy)). Thyroid hormones, which comprise benzene rings studded with iodine, are also lipid-soluble and tin can enter the jail cell.

The location of steroid and thyroid hormone binding differs slightly: a steroid hormone may bind to its receptor inside the cytosol or inside the nucleus. In either example, this binding generates a hormone-receptor complex that moves toward the chromatin in the cell nucleus and binds to a particular segment of the cell's DNA. In contrast, thyroid hormones bind to receptors already jump to Dna. For both steroid and thyroid hormones, bounden of the hormone-receptor complex with Deoxyribonucleic acid triggers transcription of a target gene to mRNA, which moves to the cytosol and directs protein synthesis by ribosomes.

Binding of Lipid-Soluble Hormones

A steroid hormone direct initiates the production of proteins within a target cell. Steroid hormones hands lengthened through the cell membrane. The hormone binds to its receptor in the cytosol, forming a receptor–hormone complex. The receptor–hormone complex then enters the nucleus and binds to the target gene on the DNA. Transcription of the gene creates a messenger RNA that is translated into the desired poly peptide inside the cytoplasm.

Pathways Involving Cell Membrane Hormone Receptors

Hydrophilic, or water-soluble, hormones are unable to diffuse through the lipid bilayer of the cell membrane and must therefore pass on their message to a receptor located at the surface of the cell. Except for thyroid hormones, which are lipid-soluble, all amino acid–derived hormones bind to prison cell membrane receptors that are located, at least in role, on the extracellular surface of the cell membrane. Therefore, they do not directly affect the transcription of target genes, but instead initiate a signaling pour that is carried out by a molecule chosen a 2nd messenger. In this case, the hormone is called a offset messenger.

The second messenger used by most hormones is cyclic adenosine monophosphate (cAMP). In the cAMP second messenger system, a h2o-soluble hormone binds to its receptor in the cell membrane (Pace one in (Figure)). This receptor is associated with an intracellular component called a K protein, and binding of the hormone activates the G-protein component (Step ii). The activated G protein in turn activates an enzyme chosen adenylyl cyclase, also known as adenylate cyclase (Footstep 3), which converts adenosine triphosphate (ATP) to camp (Step 4). Equally the 2nd messenger, cAMP activates a type of enzyme called a poly peptide kinase that is present in the cytosol (Footstep v). Activated protein kinases initiate a phosphorylation cascade, in which multiple protein kinases phosphorylate (add a phosphate grouping to) numerous and diverse cellular proteins, including other enzymes (Step 6).

Binding of Water-Soluble Hormones

Water-soluble hormones cannot diffuse through the cell membrane. These hormones must bind to a surface cell-membrane receptor. The receptor then initiates a cell-signaling pathway within the cell involving G proteins, adenylyl cyclase, the secondary messenger circadian AMP (army camp), and protein kinases. In the final step, these poly peptide kinases phosphorylate proteins in the cytoplasm. This activates proteins in the cell that carry out the changes specified by the hormone.

The phosphorylation of cellular proteins tin can trigger a wide diversity of effects, from nutrient metabolism to the synthesis of dissimilar hormones and other products. The furnishings vary according to the type of target cell, the Thousand proteins and kinases involved, and the phosphorylation of proteins. Examples of hormones that utilize cAMP every bit a second messenger include calcitonin, which is important for bone structure and regulating claret calcium levels; glucagon, which plays a office in blood glucose levels; and thyroid-stimulating hormone, which causes the release of T₃ and T_four from the thyroid gland.

Overall, the phosphorylation cascade significantly increases the efficiency, speed, and specificity of the hormonal response, equally thousands of signaling events can be initiated simultaneously in response to a very depression concentration of hormone in the bloodstream. However, the elapsing of the hormone signal is short, as cAMP is rapidly deactivated by the enzyme phosphodiesterase (PDE), which is located in the cytosol. The activity of PDE helps to ensure that a target cell'southward response ceases quickly unless new hormones arrive at the cell membrane.

Importantly, in that location are besides M proteins that decrease the levels of military camp in the cell in response to hormone binding. For example, when growth hormone–inhibiting hormone (GHIH), also known equally somatostatin, binds to its receptors in the pituitary gland, the level of cAMP decreases, thereby inhibiting the secretion of homo growth hormone.

Non all water-soluble hormones initiate the cAMP second messenger system. One common alternative system uses calcium ions as a second messenger. In this system, G proteins activate the enzyme phospholipase C (PLC), which functions similarly to adenylyl cyclase. Once activated, PLC cleaves a membrane-spring phospholipid into two molecules: diacylglycerol (DAG) and inositol triphosphate (IP₃). Like camp, DAG activates protein kinases that initiate a phosphorylation pour. At the same time, IP₃ causes calcium ions to be released from storage sites within the cytosol, such every bit from inside the shine endoplasmic reticulum. The calcium ions then deed as second messengers in 2 ways: they can influence enzymatic and other cellular activities straight, or they tin can demark to calcium-binding proteins, the most mutual of which is calmodulin. Upon bounden calcium, calmodulin is able to modulate protein kinase inside the cell. Examples of hormones that utilize calcium ions equally a second messenger organisation include angiotensin II, which helps regulate blood pressure level through vasoconstriction, and growth hormone–releasing hormone (GHRH), which causes the pituitary gland to release growth hormones.

Factors Affecting Target Cell Response

Yous will recall that target cells must take receptors specific to a given hormone if that hormone is to trigger a response. But several other factors influence the target jail cell response. For instance, the presence of a significant level of a hormone circulating in the bloodstream can cause its target cells to decrease their number of receptors for that hormone. This process is chosen downregulation, and it allows cells to become less reactive to the excessive hormone levels. When the level of a hormone is chronically reduced, target cells appoint in upregulation to increment their number of receptors. This process allows cells to be more sensitive to the hormone that is nowadays. Cells tin besides change the sensitivity of the receptors themselves to various hormones.

Two or more than hormones tin can interact to affect the response of cells in a multifariousness of ways. The iii most common types of interaction are every bit follows:

The permissive effect, in which the presence of i hormone enables another hormone to act. For example, thyroid hormones accept complex permissive relationships with certain reproductive hormones. A dietary deficiency of iodine, a component of thyroid hormones, tin can therefore affect reproductive arrangement evolution and functioning.
The synergistic effect, in which 2 hormones with like furnishings produce an amplified response. In some cases, two hormones are required for an adequate response. For case, two different reproductive hormones—FSH from the pituitary gland and estrogens from the ovaries—are required for the maturation of female ova (egg cells).
The combative effect, in which two hormones have opposing effects. A familiar example is the effect of two pancreatic hormones, insulin and glucagon. Insulin increases the liver's storage of glucose as glycogen, decreasing blood glucose, whereas glucagon stimulates the breakdown of glycogen stores, increasing blood glucose.

Regulation of Hormone Secretion

To prevent abnormal hormone levels and a potential disease state, hormone levels must be tightly controlled. The body maintains this control by balancing hormone production and degradation. Feedback loops govern the initiation and maintenance of most hormone secretion in response to various stimuli.

Function of Feedback Loops

The contribution of feedback loops to homeostasis will but exist briefly reviewed here. Positive feedback loops are characterized past the release of boosted hormone in response to an original hormone release. The release of oxytocin during childbirth is a positive feedback loop. The initial release of oxytocin begins to signal the uterine muscles to contract, which pushes the fetus toward the cervix, causing information technology to stretch. This, in turn, signals the pituitary gland to release more oxytocin, causing labor contractions to intensify. The release of oxytocin decreases after the nascence of the child.

The more than common method of hormone regulation is the negative feedback loop. Negative feedback is characterized by the inhibition of further secretion of a hormone in response to adequate levels of that hormone. This allows blood levels of the hormone to be regulated within a narrow range. An example of a negative feedback loop is the release of glucocorticoid hormones from the adrenal glands, as directed by the hypothalamus and pituitary gland. As glucocorticoid concentrations in the blood rise, the hypothalamus and pituitary gland reduce their signaling to the adrenal glands to foreclose additional glucocorticoid secretion ((Figure)).

Negative Feedback Loop

The release of adrenal glucocorticoids is stimulated by the release of hormones from the hypothalamus and pituitary gland. This signaling is inhibited when glucocorticoid levels become elevated past causing negative signals to the pituitary gland and hypothalamus.

Role of Endocrine Gland Stimuli

Reflexes triggered by both chemical and neural stimuli control endocrine activeness. These reflexes may exist simple, involving only ane hormone response, or they may be more than complex and involve many hormones, as is the case with the hypothalamic control of diverse anterior pituitary–controlled hormones.

Humoral stimuli are changes in blood levels of not-hormone chemicals, such every bit nutrients or ions, which cause the release or inhibition of a hormone to, in plow, maintain homeostasis. For case, osmoreceptors in the hypothalamus detect changes in blood osmolarity (the concentration of solutes in the blood plasma). If blood osmolarity is too loftier, meaning that the blood is non dilute enough, osmoreceptors indicate the hypothalamus to release ADH. The hormone causes the kidneys to reabsorb more water and reduce the volume of urine produced. This reabsorption causes a reduction of the osmolarity of the blood, diluting the blood to the appropriate level. The regulation of blood glucose is some other instance. Loftier blood glucose levels cause the release of insulin from the pancreas, which increases glucose uptake by cells and liver storage of glucose every bit glycogen.

An endocrine gland may also secrete a hormone in response to the presence of another hormone produced by a different endocrine gland. Such hormonal stimuli frequently involve the hypothalamus, which produces releasing and inhibiting hormones that control the secretion of a variety of pituitary hormones.

In addition to these chemical signals, hormones can also be released in response to neural stimuli. A common case of neural stimuli is the activation of the fight-or-flight response by the sympathetic nervous system. When an individual perceives danger, sympathetic neurons signal the adrenal glands to secrete norepinephrine and epinephrine. The two hormones dilate claret vessels, increase the center and respiratory rate, and suppress the digestive and immune systems. These responses boost the body's transport of oxygen to the brain and muscles, thereby improving the body's power to fight or abscond.

Everyday Connections

Bisphenol A and Endocrine Disruption You may accept heard news reports about the furnishings of a chemic called bisphenol A (BPA) in various types of food packaging. BPA is used in the manufacturing of hard plastics and epoxy resins. Common food-related items that may incorporate BPA include the lining of aluminum cans, plastic nutrient-storage containers, drinking cups, likewise as baby bottles and "sippy" cups. Other uses of BPA include medical equipment, dental fillings, and the lining of water pipes.

Enquiry suggests that BPA is an endocrine disruptor, meaning that it negatively interferes with the endocrine organisation, especially during the prenatal and postnatal evolution period. In particular, BPA mimics the hormonal effects of estrogens and has the contrary issue—that of androgens. The U.S. Food and Drug Administration (FDA) notes in their statement about BPA safety that although traditional toxicology studies accept supported the safety of low levels of exposure to BPA, recent studies using novel approaches to test for subtle effects have led to some concern about the potential effects of BPA on the brain, behavior, and prostate gland in fetuses, infants, and young children. The FDA is currently facilitating decreased apply of BPA in nutrient-related materials. Many US companies accept voluntarily removed BPA from baby bottles, "sippy" cups, and the linings of infant formula cans, and most plastic reusable water bottles sold today boast that they are "BPA free." In contrast, both Canada and the European Spousal relationship take completely banned the use of BPA in infant products.

The potential harmful effects of BPA have been studied in both animate being models and humans and include a large variety of wellness effects, such as developmental filibuster and disease. For example, prenatal exposure to BPA during the beginning trimester of man pregnancy may be associated with wheezing and aggressive beliefs during childhood. Adults exposed to high levels of BPA may experience contradistinct thyroid signaling and male person sexual dysfunction. BPA exposure during the prenatal or postnatal period of development in animal models has been observed to cause neurological delays, changes in brain construction and function, sexual dysfunction, asthma, and increased take a chance for multiple cancers. In vitro studies have also shown that BPA exposure causes molecular changes that initiate the development of cancers of the breast, prostate, and encephalon. Although these studies have implicated BPA in numerous ill wellness effects, some experts circumspection that some of these studies may be flawed and that more enquiry needs to be done. In the meantime, the FDA recommends that consumers have precautions to limit their exposure to BPA. In add-on to purchasing foods in packaging free of BPA, consumers should avert carrying or storing foods or liquids in bottles with the recycling code iii or 7. Foods and liquids should not be microwave-heated in any course of plastic: use paper, glass, or ceramics instead.

Affiliate Review

Hormones are derived from amino acids or lipids. Amine hormones originate from the amino acids tryptophan or tyrosine. Larger amino acid hormones include peptides and protein hormones. Steroid hormones are derived from cholesterol.

Steroid hormones and thyroid hormone are lipid soluble. All other amino acrid–derived hormones are h2o soluble. Hydrophobic hormones are able to diffuse through the membrane and collaborate with an intracellular receptor. In contrast, hydrophilic hormones must interact with jail cell membrane receptors. These are typically associated with a G protein, which becomes activated when the hormone binds the receptor. This initiates a signaling cascade that involves a 2nd messenger, such every bit circadian adenosine monophosphate (cAMP). Second messenger systems greatly amplify the hormone bespeak, creating a broader, more than efficient, and faster response.

Hormones are released upon stimulation that is of either chemical or neural origin. Regulation of hormone release is primarily achieved through negative feedback. Various stimuli may cause the release of hormones, but there are iii major types. Humoral stimuli are changes in ion or food levels in the blood. Hormonal stimuli are changes in hormone levels that initiate or inhibit the secretion of another hormone. Finally, a neural stimulus occurs when a nerve impulse prompts the secretion or inhibition of a hormone.

Review Questions

A newly adult pesticide has been observed to bind to an intracellular hormone receptor. If ingested, remainder from this pesticide could disrupt levels of ________.

melatonin
thyroid hormone
growth hormone
insulin

A pocket-size molecule binds to a M protein, preventing its activation. What direct effect will this have on signaling that involves camp?

The hormone will not exist able to bind to the hormone receptor.
Adenylyl cyclase will not be activated.
Excessive quantities of campsite will exist produced.
The phosphorylation cascade will exist initiated.

A student is in a car accident, and although not injure, immediately experiences educatee dilation, increased center rate, and rapid breathing. What blazon of endocrine organisation stimulus did the student receive?

humoral
hormonal
neural
positive feedback

Critical Thinking Questions

Compare and contrast the signaling events involved with the second messengers camp and IP_three.

In both cAMP and IP₃–calcium signaling, a hormone binds to a cell membrane hormone receptor that is coupled to a G protein. The 1000 protein becomes activated when the hormone binds. In the case of cAMP signaling, the activated G poly peptide activates adenylyl cyclase, which causes ATP to be converted to cAMP. This 2d messenger can then initiate other signaling events, such equally a phosphorylation cascade. In the case of IP₃–calcium signaling, the activated G poly peptide activates phospholipase C, which cleaves a membrane phospholipid chemical compound into DAG and IP₃. IP₃ causes the release of calcium, another second messenger, from intracellular stores. This causes further signaling events.

Describe the machinery of hormone response resulting from the binding of a hormone with an intracellular receptor.

An intracellular hormone receptor is located inside the cell. A hydrophobic hormone diffuses through the jail cell membrane and binds to the intracellular hormone receptor, which may be in the cytosol or in the cell nucleus. This hormone–receptor complex binds to a segment of DNA. This initiates the transcription of a target gene, the end result of which is protein assembly and the hormonal response.

Glossary

adenylyl cyclase: membrane-bound enzyme that converts ATP to cyclic AMP, creating military camp, as a result of G-poly peptide activation

circadian adenosine monophosphate (cAMP): 2nd messenger that, in response to adenylyl cyclase activation, triggers a phosphorylation cascade

diacylglycerol (DAG): molecule that, like cAMP, activates poly peptide kinases, thereby initiating a phosphorylation pour

downregulation: decrease in the number of hormone receptors, typically in response to chronically excessive levels of a hormone

first messenger: hormone that binds to a jail cell membrane hormone receptor and triggers activation of a second messenger system

G protein: poly peptide associated with a cell membrane hormone receptor that initiates the next stride in a second messenger system upon activation by hormone–receptor binding

hormone receptor: protein within a prison cell or on the cell membrane that binds a hormone, initiating the target cell response

inositol triphosphate (IP_three): molecule that initiates the release of calcium ions from intracellular stores

phosphodiesterase (PDE): cytosolic enzyme that deactivates and degrades cAMP

phosphorylation cascade: signaling event in which multiple protein kinases phosphorylate the next poly peptide substrate by transferring a phosphate grouping from ATP to the protein

poly peptide kinase: enzyme that initiates a phosphorylation cascade upon activation

2nd messenger: molecule that initiates a signaling pour in response to hormone binding on a cell membrane receptor and activation of a M protein

upregulation: increment in the number of hormone receptors, typically in response to chronically reduced levels of a hormone

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Source: https://opentextbc.ca/anatomyandphysiologyopenstax/chapter/hormones/