Endocrine System Flashcards

Preservation of Homeostasis

• Homeostasis is the condition of equilibrium or balance in the body’s internal environment due to the interplay of the body’s many regulatory processes.

• Homeostasis is the result of optimal structure and function interaction.

  • The function is whole because the structures are whole, and the structures are whole because the function is whole.

• A disorder or disease results when there is an abnormality of structure or function.

• The interplay of the body’s processes depends upon communication.

• Each cell must “know” what the other cells are doing, in order to respond and act so to maintain homeostasis. This is done through negative feedback.

• Negative feedback is when an increase in one physiological parameter leads to a physiological process that results in a decrease in the parameter, and conversely, a decrease in the parameter leads to a process that results in an increase in the parameter.

Types of Intercellular Communication

• There are four types of ways that the cells in the body communicate with each other:

  1. Direct communication

  2. Paracrine communication

  3. Endocrine communication

  4. Synaptic communication

Direct Communication

• This occurs between two cells of the same type where the cells are in extensive physical contact, therefore the communication is limited to these two cells only.

• The transmission of information occurs through gap junctions.

• Gap junctions are regions between two cells that permit the movement of ions, small solutes or lipid soluble materials from one cell to the other and vice versa.

• This occurs with epithelial cells and cardiac cells.

Paracrine Communication

• This type of communication is not as limited as direct.

• Here, information, in the form of cellular chemicals called paracrine factors, are released from one cell into the surrounding extracellular fluid.

• The paracrine factors then diffuse to the many neighboring cells in the same tissue.

• The concentration of these factors are usually so low that distant cells and tissues are not affected.

• Prostaglandins are examples of this type of factor.

Endocrine Communication

• This is the least limited type of communication.

• Here, cells release chemicals called hormones directly into the bloodstream. The hormones then travel throughout the body.

• However, the hormones are specific to what cells they will affect. These cells are called target cells. The target cells have receptors that the hormones attach to, in order for the target cell to “read” the hormonal information or commands and react in a certain way.

Hormones

• Hormones may affect a target cell by:

  1. Stimulating the synthesis of an enzyme or structural protein not already present in the cytoplasm via transcription and translation.

  2. Increase or decrease the rate of synthesis of an enzyme or protein.

  3. Turn an existing enzyme or membrane channel “on” or “off” by changing its shape or structure.

• Because of the powerful influence hormones have on target cells, a single hormone can alter the metabolism of multiple tissues or entire organs simultaneously.

• The effects of a single hormone may last for days.

• The observable effects of hormones are at their greatest during embryological and fetal development, growth and puberty.

Synaptic Communication

• The nervous system also relies on chemical communication. This is accomplished through the release of neurotransmitters into the synaptic cleft.

• This type of communication is again very limited to adjacent neurons or muscle cells that have specific receptor for the neurotransmitter.

• This is done in order to propagate the action potential.

The Endocrine System

• This includes all the cells and tissues in the body that produce hormones or paracrine factors.

• It is the fact of the release of these chemicals directly into the bloodstream that defines these cells or tissues as endocrine. This characteristic distinguishes them from exocrine glands that secrete their products into ducts.

Classes of Hormones

• There are three groups of hormones based on their chemical structure:

  1. Amino acid derivatives

  2. Peptide hormones

  3. Lipid derivatives

Amino Acid Derivatives

• These are small molecules that are structurally related to amino acids, the building blocks of proteins.

• Specifically they are synthesized from the amino acids tyrosine and tryptophan.

• Tyrosine derivatives include thyroid hormones and the catecholamines: epinephrine, norepinephrine and dopamine.

• Tryptophan derivatives include melatonin produced by the pineal gland.

Peptide Hormones

• These are chains of amino acids, and therefore larger than the previous class of hormones.

• The two groups are:

  1. Glycoproteins: e.g.: thyroid stimulating hormone (TSH), lutinizing hormone (LH), follicle-stimulating hormone (FSH).

  2. Other than Glycoproteins: e.g.: antidiuretic hormone (ADH), oxytocin, growth hormone (GH), prolactin (PRL).

Lipid Derivatives

• The two classes are:

  1. Eicosanoids: small molecules with a five-carbon ring at one end and derived from arachidonic acid (a 20-carbon fatty acid).

  2. Steroid hormones: lipids derived from cholesterol.

Eicosanoids

• These are mostly the paracrine factors of the body:

  1. Leukotrienes: released by white blood cells (aka leukocytes). Important in coordinating tissue responses to injury or disease.

  2. Prostaglandins: produced in most tissues of the body and may be converted to thromboxanes and prostacyclins. Prostaglandins may be secreted by injured cells or tissues causing the increase of blood flow to the injured area causing it to become red and warm. They are the “pain” producing chemicals.

Steroid Hormones

• These include the sex hormones:

  1. Androgens: secreted by the testes, e.g: testosterone.

  2. Estrogens and progestins: secreted by the ovaries. E.g.: estrogen, progesterone.

• They also include corticosteroids (produced by the cortex of the adrenal glands) and calcitriol (produced by the kidneys).

Secretion of Hormones

• Once hormones are released into the blood stream, they may either circulate freely or bind to a special carrier protein.

• A freely circulating hormone remains functional for less than one hour and becomes inactivated in the bloodstream by either binding to the receptors of the target cells, absorbed and broken down by cells in the liver or kidneys, or broken down by enzymes in the blood plasma or interstitial fluid.

• Hormones that bind to the special carrier proteins remain in circulation much longer, up to several months.

• Thyroid and steroid hormones are examples of these hormones.

Hormone Receptors

• Receptors of target cells may be on the plasma membrane or within the cytoplasm.

• Water-soluble hormones, such as the catecholamines or peptide hormones, cannot penetrate the plasma membrane, therefore their receptors are located on the outer surface of the plasma membrane (extracellular receptors).

• Eicosanoids are lipid derivatives and therefore lipid-soluble. They are able to penetrate the plasma membrane to reach receptors on the inner surface of the membrane (intracellular receptors).

First and Second Messengers

• If a hormone binds to receptors in the plasma membrane, they cannot directly affect the activities inside the cell (such as transcription and translation).

• Therefore, the hormone, called the first messenger, needs an intracellular intermediary, called the second messenger, to exert its effects.

Second Messengers

• There are three important second messengers:

  1. Cyclic-AMP (cAMP): a derivative if ATP

  2. Cyclic-GMP (cGMP): a derivative of GTP, another high energy compound.

  3. Calcium ions

• The link between the first and second messenger involves a G protein, which is an enzyme complex coupled to a membrane receptor. This protein when activated will bind to GTP.

G Proteins and cAMP

• When a hormone binds to a receptor on the plasma membrane, the G protein becomes activated.

• The activated G protein then activates the enzyme adenylate cyclase which converts ATP to cyclic-AMP.

• Cyclic-AMP activates the enzyme kinase which accelerates the metabolic activity of the target cell ultimately resulting in the opening of ion channels or the activation of enzymes.

• Calcitonin, PTH, ADH, ACTH, epinephrine, FSH, LH, TSH and glucagon all produce their effects by this mechanism.

• In order to prevent the cell from “burning out”, another enzyme called phosphodiesterase (PDE) found in the cytoplasm inactivates the c-AMP once the desired effect is accomplished (negative feedback).

G Proteins and Calcium Ions

• An activated G protein can trigger either the opening of calcium ion channels in the plasma membrane or the release of calcium ions from intracellular stores.

• The activated G protein will activate the enzyme phospholipase C (PLC) which causes the production of diacylglycerol (DAG) and inositol triphosphate (IP3) in the plasma membrane.

• IP3 diffuses into the cytoplasm and causes the release of calcium ions from intracellular reserves (smooth endoplasmic reticulum).

• The calcium ions and DAG activates the membrane protein protein kinase C (PKC) which will open up the calcium ion channels allowing extracellular calcium ions to enter the cell (positive feedback).

• These ions bind with an intracellular protein called calmodulin which accelerates the metabolic activity in the cell.

• Epinephrine, norepinephrine, oxytocin and several eicosanoids produce their effects by this positive feedback mechanism.

Hormones and Intracellular Receptors

• Steroids are lipid soluble and can penetrate the plasma membrane easily. Their receptors are found in the cytoplasm or nucleus. Therefore they can quickly alter the rate of transcription, translation and protein synthesis causing a possible change in the metabolism and structure of the target cell.

• For example, testosterone stimulates the production of enzymes and structural proteins in skeletal muscle fibers, causing and increase of muscle size and strength.

Hormones and Intracellular Receptors

• Thyroid hormones are lipid soluble because they are very small in size.

• Therefore they are able to cross the plasma membrane by a transport mechanism very easily. Their receptors are in the mitochondria (for increase of ATP production) or the nucleus (for transcription rate change).

Endocrine Reflexes

• Simple endocrine reflexes are when endocrine cells secrete one hormone in response to changes in the composition of the extracellular fluid, causing the target cells to adjust their activity and restore homeostasis. They control hormone secretion by the heart, pancreas, parathyroid glands and digestive tract.

• Complex endocrine reflexes involve one or more intermediary steps and two or more hormones. These reflexes include activity of the hypothalamus in the diencephalon.

Hypothalamus

• There are three mechanisms of hypothalamic control over endocrine function:

  1. The hypothalamus secretes regulatory hormones, special hormones that control endocrine cells in the adenohypophysis (anterior lobe) of the pituitary gland. The adenohypophysis, in turn, secretes hormones that control the endocrine cells of the thyroid, adrenal cortex and reproductive organs.

  2. The hypothalamus itself is a endocrine organ. It synthesizes hormones, transports then along axons within the infundibulum (the “stem” of the pituitary gland) to the neurohypophysis (posterior lobe of the pituitary gland) where it would be released into the bloodstream.

  • The two hormones produces this way are ADH and oxytocin.

  1. The hypothalamus contains autonomic centers that exert direct neural control over the endocrine cells of the adrenal medullae.

• When the sympathetic division is activated (“fight or flight”) the hypothalamus commands the adrenal medullae to secrete epinephrine and norepinephrine into the bloodstream.

  • This process is specifically called a neuroendocrine reflex.

The Pituitary Gland

• Also called the hypophysis, it is a small, oval gland protected in the sella turcica of the sphenoid bone and secured in place by a dural sheet called the diaphragma sellae.

• It hangs inferior to the hypothalamus and is connected by a funnel-shaped structure called the infundibulum.

• The anterior lobe of the pituitary is called the adenohypophysis which secretes seven peptide hormones.

• The posterior lobe of the pituitary gland is called the neurohypophysis and secretes two peptide hormones.

Adenohypophysis

• Subdivided into three regions:

  1. Pars distalis: largest and most anterior part

  2. Pars tuberalis: wraps around the inferior part of the infundibulum.

  3. Pars intermedia: a narrow band bordering the neurohypophysis.

Hypophyseal Portal System

• An extensive capillary network radiates through the adenohypophysis giving every endocrine cell immediate access to the circulatory system.

• These capillaries are called fenestrated capillaries because they are lined with endothelial cells that are unusually permeable so larger hormones can enter the bloodstream easily.

• The median eminence which is a swollen area at the base of the infundibulum, is supplied by the superior hypophyseal artery which brings blood from the heart.

• The superior hypophyseal artery brings oxygenated blood to a capillary network in the median eminence which is then carried by portal vessels that deliver the blood to another capillary network in the adenohypohysis.

• From there, blood and hormones leave via hypophyseal veins in order to reach the target cells.

Hormones of the Adenohypophysis

1. Thyroid-Stimulating Hormone (TSH):

   • targets the thyroid gland and triggers the release of thyroid hormones (thyroxine, triiodothyronine).

   • It is secreted in response to the production of thyrotropin-releasing hormone, which is secreted by the hypothalamus.

2. Adrenocorticotropic Hormone (ACTH):

   • stimulates the release of glucocorticoids (steroids that affect glucose metobolism) by the adrenal cortex.

   • ACTH is released in response to the production of corticotropin-releasing hormone (CRH), by the hypothalamus.

• Gonadotropins are hormones that regulate the activities of the gonads (testes and ovaries). They are released by the adenohypophysis in response to the production of gonadotropin-releasing hormone (GnRH) from the hypothalamus

• Lack of these hormones lead to hypogonadism where people cannot undergo sexual maturation and are sterile or infertile.

• The two gonadotropins are follicle-stimulating hormone and luteinizing hormone.

1. Follicle-Stimulating Hormone (FSH):

   • promotes follicle development in females and, in combination with LH, stimulates the secretion of estrogens by ovarian cells.

   • In males, FSH stimulates nurse cells, that promote physical maturation of sperm cells.

2. Luteinizing Hormone (LH):

   • induces ovulation (production of ova in females), promotes the secretion of estrogens and progestins by the ovary that prepare the body for possible pregnancy.

   • In males, LH stimulates the production of sex hormones called androgens (e.g. testosterone) by the interstitial cells of the testes.

3. Prolactin (PRL):

   • helps stimulate mammary gland development and milk production during and after pregnancy.

4. Growth Hormone (GH):

   • stimulates cell growth and replication by accelerating the rate of protein synthesis.

   • The production of GH is regulated by growth hormone-releasing factor (GH-RH) and growth hormone-inhibiting hormone (GH-IH).

5. Melanocyte Stimulating Hormone (MSH):

   • stimulates the melanocytes of the skin increasing the production of the yellow-brown pigment called melanin.

   • It is secreted during exposure to the sun and may be administered synthetically to obtain a “sunless tan”.

Hormones of the Neurohypophysis

1. Antidiuretic Hormone (ADH):

   • released in response to a decrease in blood volume or pressure or increase of solute concentration of the blood picked up by osmoreceptors.

   • The function is to decrease the amount of water lost in the kidneys and vasoconstriction of peripheral blood vessels in order to increase the blood pressure.

   • ADH release is inhibited by alcohol, which explains the “breaking the seal” phenomena.

   • Diabetes insipidus is the condition where not enough ADH is produced therefore causing excess loss of water in the urine (polyuria) resulting in constant thirst, dehydration, electrolyte imbalances and possible death.

   • Desmopressin is a synthetic form of ADH and is used to treat diabetes insipidus.

2. Oxytocin (OXT):

   • stimulates the smooth muscle contractions of the uterus promoting labor and delivery.

   • It also promotes the ejaculation of milk from the nipples after pregnancy as the milk let-down reflex.

   • In men, OXT stimulates smooth muscle contraction in the sperm duct and prostate gland to allow emission (ejection of sperm and gland secretions into the urethra before ejaculation).

Thyroid Gland

• Located across the anterior trachea, this gland has two lobes united by a narrow connection called the isthmus.

• Also has an extensive blood supply in order to easily deposit its hormones into the bloodstream.

• Contains thyroid follicles cells which are hollow spheres lined with simple cuboidal epithelium. Within these cells are follicle cavities that contain the colloid (fluid and dissolved proteins).

• The follicle cells synthesize a protein called thyroglobulin which is deposited into the colloid. This protein contains the amino acid tyrosine, which is the building block of thyroid hormones.

• Iodide ions absorbed in the bloodstream from ingested foods in the GI tract are delivered into the colloid of the follicle cells and bind to the tyrosine of the thyroglobulin protein.

• If the molecule contains 4 iodide ions, it forms the hormone thyroxine (T4). If the molecule contain 3 iodide ions the hormone is triiodothyronine (T3).

• Thyroid stimulating hormone (TSH) stimulates the transport of iodide ions into the follicle cells causing the production of the thyroid hormones. It also stimulates the release of these hormones into the bloodstream.

Function of Thyroid Hormones

• Thyroid hormones binding to receptor in the target cell’s mitochondria increase ATP production, increasing energy and metabolic rate of the cell.

• They also help control growth and development of skeletal, muscular and nervous systems in growing children.

Hypothyroidism v. Hyperthyroidism

• Hypothyroidism (aka myxedema) results from the deficiency of T3 and T4 directly (underactive thyroid) or a deficiency of TSH (underactive pituitary gland).

  • Symptoms in children include reduction of growth velocity and arrest of pubertal development.

  • In adults the symptoms may be non-pitting edema, dryness of skin and swelling of the face, hair loss on the scalp and lateral 1/3 of the eyebrows, carpal tunnel syndrome, cold sensitivity, pericardial and pleural effusions or bradycardia.

  • A goiter may be present if the thyroid is being destroyed and replaced by scar tissue as in the case of Hashimoto’s autoimmune thyroiditis.

• Hyperthyroidism (thyrotoxicosis) is due to the excess secretion of T3 and T4.

  • Grave’s Disease is a common cause of hyperthyroidism. It is characterized by a diffuse goiter, pretibial myxedema, tachycardia, tremor, weight loss, exophthalmos and sensitivity to hot weather. Treatment are anti-thyroid drugs or thyroidectomy.

Thyroid Gland

• C (clear) cells (aka parafollicular cells) are found between the follicular cells.

• They secrete the hormone calcitonin (CT) which decreases calcium ion concentrations in the body fluids.

• In the case that the body has too much calcium in the body fluids, the C cells will secrete calcitonin which inhibits the activity of osteoclasts in bone and stimulates calcium excretion at the kidneys.

Parathyroid Glands

• There are two pairs of these glands located in the posterior surface of the thyroid gland.

• The parathyroid cells produce parathyroid hormone (PTH) which has the opposite function of calcitonin.

  • If calcium ion levels in body fluids fall below normal levels, PTH is secreted inhibiting osteoblastic activity and triggers the production of more osteoclasts.

  • It also enhances the resorption of calcium ions at the kidneys and stimulates the production of calcitriol by the kidneys which increases the absorption of calcium and phosphate by the GI tract.

Adrenal Glands

• Also known as the suprarenal glands, they are pyramid-shaped glands located on the superior surfaces of the kidneys.

• Like every other endocrine gland, they are very vascular.

• Each are subdivided into two parts: the adrenal cortex and adrenal medulla.

Adrenal Cortex

• There are three zones in the cortex:

  1. Zona Glomerulosa: outermost region that produces the mineralocorticoids.

  • These are hormones that affect the electrolyte composition of the body fluids.

  • Aldosterone is the main mineralocorticoid and stimulates the conservation of sodium ions as well as the elimination of potassium ions at the kidneys, sweat glands, salivary glands, and pancreas.

  1. Zona Fasciculata: produces steroid hormones called glucocorticoids which regulate glucose metabolism.

  • The main glucocortioid is cortisol and is secreted in response to ACTH.

  • It accelerates the rates of glucose synthesis and glycogen production.

  • It also breaks down adipose tissue and other tissues in order to release fatty acids and proteins into the blood for immediate energy for cells.

  • Glucocorticoids have an anti-inflammatory effect by inhibiting the activity of WBCs and components of the immune system, as well as inhibiting the release of histamines.

  • However, overuse of synthetic glucocorticoids, such as cortisone, prevents the process of healing and may lead to tissue degeneration.

Cortisol

• Cortisol is released in response to sympathetic responses, including stress.

  • Chronic stress can lead to over-secretion of cortisol and may lead to excessive breakdown of tissue in the body that could result in exhaustion, chronic pain and Type II diabetes.

• Cushing’s syndrome is due to the release of glucocorticoids in response to excess ACTH secreted by the pituitary gland or excess use of synthetic glucocorticoids.

  • Symptoms include thinning of the skin, striae, muscle weakness, hair loss, weight gain, increased thoracic kyphosis (“buffalo hump”), “moon face” and hirsutism.

  1. Zona reticularis: deepest of the zones. Under stimulation of ACTH, this zone produces small quantities of androgens.

  • Once released into the blood, the androgens are converted to estrogens.

  • These androgens stimulate the development of pubic hair in prepubescent boys and girls.

  • While not important in adult men, in adult women these androgens promote muscle mass, blood cell formation and libido support.

Adrenal Medulla

• This is the core of the adrenal glands which contain large, round cells innervated by preganglionic sympathetic fibers.

• Secretion is controlled by the sympathetic division of the ANS.

• It secretes epinephrine and norepinephrine.

• Epinephrine make up 75-80% of the secretions by the medulla. The remainder is norepinephrine.

• Most cells of the body are the target cells. Their function is increase in cardiac activity, blood pressure, glycogen breakdown, blood glucose levels and the release of lipids by adipose tissue.

Pineal Gland

• Part of the epithalamus, it is located in the posterior roof of the third ventricle.

• Contains secretory cells called pinealocytes that secrete the hormone melatonin. These cells are influenced by visual pathways and therefore produce more melatonin at night than in the day.

• Functions of this hormone is inhibiting reproductive functions by slowing the maturation of the sperm, oocytes and organs, protects against free radicals (therefore is an anti-oxidant), setting circadian rhythms. Increased melatonin secretion in times of extended darkness has been suggested as the cause for seasonal affective disorder.

Pancreas

• Located in the abdominal cavity between the inferior stomach and superior small intestine, this organ is both an endocrine and exocrine gland.

• The vast majority of the pancreas produces digestive enzymes that is sent to the small intestine through ducts. This is the exocrine pancreas.

• The endocrine pancreas consists of cells called pancreatic islets or islets of Langerhans. Each islet contains alpha cells, which produce the hormone glucagon, and beta cell which produces the hormone insulin.

• Insulin is a peptide hormone released into the bloodstream when blood-glucose levels exceed normal levels (70-110 mg/dl), when high blood-amino acid levels are too high, or by parasympathetic activation.

• Insulin facilitates the uptake of glucose by target cells (insulin-dependent cells). Some cells are insulin-independent, such as cells in the brain, kidney, lining of the GI tract and RBCs, because they can absorb and utilize glucose without insulin stimulation.

• Glucagon is secreted when glucose levels fall below normal.

• This hormone stimulates the breakdown of glycogen stored in skeletal muscle and liver cells, the breakdown of triglycerides in adipose tissue and stimulates the production of glucose in the liver (gluconeogenesis).

Diabetes Mellitus

• Type I or insulin-dependent diabetics are born without or have their beta cells destroyed (virus, autoimmune). They are unable to produce insulin and require multiple injections daily in order to live.

• Type II or non-insulin-dependent diabetes results when the insulin receptors on the cell membrane become desensitized.

  • This is due to a phenomenon called down-regulation, where a presence of a hormone triggers a decrease in the number of hormone receptors. Therefore, when levels of insulin are high, such as in the case of a poor diet and constant stress, cells become less sensitive to it.

• Diabetes mellitus may lead to diabetic retinopathy, nephropathy, peripheral neuropathies, myocardial infarctions and trophic changes in the skin (ulceration, loss of hair, nail deformations).

Kidneys

• Calcitriol: a steroid that is secreted in response to the presence of PTH.

  • A type of vitamin D, calcitriol stimulates the absorption of calcium and phosphate ions in the GI tract, the formation and activity of osteoclasts, resorption of calcium ions in the kidneys, and suppresses PTH production.

• Erythropoietin: a peptide hormone released in response to low oxygen levels in the kidney tissue.

  • This hormone stimulates the production of RBCs in bone marrow, which will in turn deliver more oxygen to the kidneys.

• Renin: secreted in response to sympathetic stimulation or a decline in renal blood flow.

  • Once secreted in the blood, a cascade occurs called the renin-angiotensin system.

  • Renin converts angiotensinogen (protein produced by the liver) into angiotensin I.

  • When angiotensin I travels to the lungs, it is converted to angiotensin II, which stimulates the secretion of aldosterone from the adrenal cortex and ADH at the neurohypophysis.

  • Together both hormones restricts salt and water loss at the kidneys, increasing thirst, blood pressure and blood volume.

Heart

• The endocrine cells of the heart are those cardiac muscle cells that are found in the walls of the atria and ventricles.

• If blood volume is too great, these cells stretch excessively and secrete natriuretic peptides which function as the opposite of angiotensin II.

• They promote the loss of water and sodium ions at the kidneys and inhibit the secretion of aldosterone and ADH, causing a decrease in blood pressure and volume.

Thymus

• Located in the mediastinum, it secretes a hormone called thymosin, which promotes the development and maturation of lymphocytes (WBCs responsible for immunity).

Gonads

• In males, interstitial cells in the testes produce androgens.

  • Testosterone is an androgen that supports the maturation of sperm, protein synthesis in skeletal muscles, male secondary sex characteristics (facial hair, deep voice), and associated behaviors.

• Nurse cells in the testes secrete inhibin that will target the adenohypophysis in order to inhibit the production of FSH.

• In females, the steroid hormones produced by follicular cells are called estrogens.

  • Estradiol is the main estrogen and functions to support follicle maturation, female secondary sex characteristics, and associated behavior.

  • Inhibin is also secreted by the follicular cells and acts the same way as that in the male.

• Progestins are hormones secreted by the corpus luteum (follicular cell after it releases the oocyte).

  • Progesterone is the principle progestin and prepares the uterus for implantation, the mammary glands for secretory activity.

Adipose Tissue

• Leptin is a peptide hormone released from adipose tissue when we eat.

• As the adipose absorbs glucose and lipids and synthesizes triglycerides for storage, it releases leptin which binds to neurons in the hypothalamus resulting in a sense of satiation and the suppression of appetite.