The Endocrine System Part A

16

Objectives

 List the major endocrine organs, and describe their body locations.  Distinguish between hormones, paracrines, and autocrines.  Chemical Classification  Mechanisms of hormone action  Interaction of different hormones acting on the same target cell.  Explain how hormone release is regulated.  Major Endocrine Organs  Hypothalamus and the pituitary gland.  Adenohypophyseal hormones.  Neurohypophysis, and its hormones

Objectives

 Thyroid gland  Parathyroid hormone  Adrenal gland, its hormones and their physiological effects.  Pancreatic hormones  Hormones of the testes and ovaries.  Briefly describe the importance of thymic and pineal hormones.  Other Hormone-Producing Structures  Hormone produced by the heart, and localize enteroendocrine cells.  Hormonal functions of the placenta, kidney, skin, and adipose tissue.

Endocrine System: Overview  Gland--?  Endocrine or ductless glands (endo-within; crine Discharge hormones into the bloodstream directly rather than through ducts e.g., pituitary, thyroid, adrenal.  Exocrine glands  Discharge their products (which are not hormones) through ducts e.g., salivary, sweat.  Endocrine system – Group of ductless glands that secrete hormones necessary for normal growth and development, reproduction, and homeostasis. (Endocrinology)  It is the body’s second great controlling system which influences metabolic activities of cells by means of hormones
to secrete)

 Endocrine System: Overview Endocrine glands –  Pituitary  Thyroid  Parathyroid  Adrenal  Pineal and Thymus  The pancreas and gonads produce both hormones and exocrine products  The hypothalamus has both neural functions and releases hormones (Neuro-endocrine Organ)  Other tissues and organs that produce hormones –  Adipose cells release Leptin (regulate fat storage in the body)  Pockets of Hormone producing cells are found in the  walls of the small intestine, Stomach, Kidneys,

Major Endocrine Organs and their Location

Autocrines and Paracrines (local chemical messengers)

 Autocrines – chemicals that exert their effects on the same cells that secrete them  For example, certain prostaglandins released by smooth muscle cells cause those smooth muscle cells to contract.  Paracrines – locally acting chemicals that affect cells other than those that secrete them  e.g., somatostatin released by one population of pancreatic cells inhibits the release of insulin by a different population of pancreatic cells.  These are not considered hormones since hormones are long-distance chemical signals

 Hormones (hormon-to excite) – chemical Hormones substances secreted by cells into the extracellular fluids  Regulate the metabolic function of other cells  Have lag times ranging from seconds to hours  Tend to have prolonged effects  Are classified as amino acid-based hormones, or steroids  The major processes controlled and integrated by these are 1. reproduction; growth and development; 2. mobilization of body defenses; 3. maintenance of electrolyte, water, and nutrient balance of the blood; and 4. regulation of cellular metabolism and energy

 Types of Hormones hormones belong to this class, Amino acid based – most including:  Simple AA derivatives eg Amines, thyroxine from tyrosine  Peptides (short chains of AA) (< 100 AA)  Protein (Long polymers of AA) (100-200 AA)  Steroids – (from cholesterol)  Gonadal and adrenocortical hormones  Eicosanoids – leukotrienes and prostaglandins  These biologically active lipids (made from arachidonic acid) are released by nearly all cell membranes.  Leukotrienes  mediate inflammation and some allergic reactions.  Prostaglandins have multiple targets and effects,  regulating blood pressure and increasing the expulsive uterine contractions of birth  Enhancing blood clotting, pain, and inflammation.  Highly localized effects, affecting only nearby cells, they InterActive Physiology : Endocrine System: Orientation generally act as paracrines and autocrines not fit in PLAY
®

Types of Hormones

1. Tyrosine derivatives include 1. Hydrophilic catecholamines  dopamine, epinephrine and norepinephrine 2. Lipophilic thyroid hormones (T3, T4).  Peptide hormones and glycoprotein hormones are hydrophilic hormones stored in secretory granules and released by exocytosis as required.  Steroid hormones and calcitriol are chemically related lipophilic hormones metabolized from cholesterol They are not stored, but are synthesized as needed.

Hormone Action  Hormones act only on Target cells  Precise Response depends on target cell types  eg Epineprine  Vasoconstriction of smooth muscle of Blood vessels  Bronchodilation  Hormones produce one or more of the following cellular changes in target cells  Alters plasma membrane permeability or membrane potential, or both, by opening or closing ion channels  Stimulates synthesis of proteins or regulatory molecules such as enzymes within the cell  Activates or deactivates enzymes  Induces secretory activity

Mechanism of Hormone Action  The mechanism depends on

 Chemical nature of the hormone  Cellular location of the receptor  Hormones alter target cell activity by one of two mechanisms  Second messengers involving regulatory G proteins  Direct gene activation  Water-soluble hormones (all amino acid–based hormones except thyroid
hormone)

(Guanine Neuclotide - binding proteins)

Act on receptors in the plasma membrane coupled via regulatory molecules (G proteins) to one or more intracellular second messengers which mediate the target cell’s response.  Lipid-soluble hormones (steroid and thyroid hormones)  Act on intracellular receptors, directly activating genes.  The precise response depends on the type of the target 

Hydrophilic hormones : (G-protein Coupled 2nd messengers)

Lipid-soluble hormones: (Intracellular Receptors Mediated)

Amino Acid-Based Hormone Action: cAMP Second Messenger

 Hormone (first messenger) binds to its receptor, which then binds to a G protein  The G protein is then activated as it binds GTP, displacing GDP  Activated G protein activates the effector enzyme adenylate cyclase  Adenylate cyclase generates cAMP (second messenger) from ATP  cAMP activates protein kinases, which then cause cellular effects

Amino Acid-Based Hormone Action: cAMP Second Messenger

Amino Acid-Based Hormone Action: PIP-Calcium
 Hormone binds to the receptor and activates G protein  G protein binds and activates a phospholipase enzyme  Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers)  DAG activates protein kinases; IP3 triggers release of Ca2+ stores  Ca2+ (third messenger) alters cellular responses

Amino Acid-Based Hormone Action: PIP-Calcium

cAMP Second Messenger & Ca++ Pathways

Steroid Hormones

 Steroid hormones and thyroid hormone diffuse easily into their target cells  Once inside, they bind and activate a specific intracellular receptor  The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein  This interaction prompts DNA transcription to produce mRNA  The mRNA is translated into proteins, which bring about a cellular effect

Steroid Hormones

Steroid Hormones: (Aldosteron)

Target Cell Specificity

 Hormones circulate to all tissues but only activate cells referred to as target cells  Target cells must have specific receptors to which the hormone binds  These receptors may be intracellular or located on the plasma membrane  Examples of hormone activity  ACTH receptors are only found on certain cells of the adrenal cortex  Thyroxin receptors are found on nearly all cells of the body

Target Cell Activation  Target cell activation depends on three factors

 Blood levels of the hormone  Relative number of receptors on the target cell  The affinity of those receptors for the hormone  Up-regulation – target cells form more receptors in response to the hormone  Down-regulation – target cells lose receptors in response to the hormone  Hormones influence the number and affinity not only of their own receptors but also of receptors that respond to other hormones.  For example, progesterone induces a loss of estrogen receptors in the uterus, On the other hand, estrogen causes the same cells to produce more progesterone receptors, enhancing their ability to respond to progesterone.
PLAY InterActive Physiology®: Endocrine System: Actions of Hormones on Target Cells

Hormone Concentrations in the Blood

 Hormones circulate in the blood in two forms – free or bound  Steroids and thyroid hormone are attached to plasma proteins  All others are free to move  Concentrations of circulating hormone reflect:  Rate of release  Speed of inactivation and  removal from the body  Hormones are removed from the blood by:  Degrading enzymes  The kidneys  Liver enzyme systems

Interaction of Hormones at Target Cells
 Three types of hormone interaction  Permissiveness – one hormone cannot exert its effects without another hormone being present  For example, the development of the reproductive system by its hormones but thyroid hormone is necessary for normal timely development of reproductive structures  Synergism – more than one hormone produces the same effects on a target cell  For example, both glucagon (produced by the pancreas) and epinephrine cause the liver to release glucose to the blood; when they act together, the amount of glucose released is about 150% of what is released when each hormone acts alone.  Antagonism – one or more hormones opposes the action of another hormone  Insuline vs glucagon

Hormone Action, Release and Control

The duration of hormone action is limited, ranging from 10 seconds to several hours, depending on the hormone.  Hormonal blood levels must be precisely and individually controlled to meet the continuously changing needs of the body.  Blood levels of hormones:  Are controlled by negative feedback systems  Vary only within a narrow desirable range 
PLAY InterActive Physiology®: Endocrine System: Biochemistry, Secretion, and Transport of Hormones

Feed Back Mechanisms

Feed Back Mechanisms

Control of Hormone Release

 Hormones are synthesized and released in response to following stimuli  Humoral  Neural  Hormonal

Humoral Stimuli

 Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients  Example: concentration of calcium ions in the blood  Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)  PTH causes Ca2+ concentrations to rise and the stimulus is removed

Humoral Stimuli

Neural Stimuli

 Neural stimuli – nerve fibers stimulate hormone release  Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines

Hormonal Stimuli

 Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs  The hypothalamic hormones stimulate the anterior pituitary  In turn, pituitary hormones stimulate targets to secrete still more hormones  eg, Thyroid, Adrenal, Gonads etc.

Hormonal Stimuli

Nervous System Modulation

 The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms  The nervous system can override normal endocrine controls  For example, control of blood glucose levels  Normally the endocrine system maintains blood glucose (90-110mg/100ml of blood)  Under stress, the body needs more glucose  The hypothalamus and the sympathetic nervous system are activated to supply ample glucose

Functional classification of hormones
 Hormones are classified into two functional categories: 1. Trophic hormones 2. Nontrophic hormones  Trophic hormone  Acts on another endocrine gland to stimulate secretion of its hormone.  For example, Thyrotropin or TSH stimulates the secretion of thyroid hormones.  ACTH stimulates the adrenal cortex to secrete the hormone cortisol.  Nontrophic hormone  Acts on nonendocrine target tissues.  For example, Parathormone bone tissue to stimulate the release of calcium into the blood.  Aldosterone acts on the kidney to stimulate the reabsorption of sodium into the blood.

Major Endocrine Organs 1. 2. 3. 4. 5. 6. 7. 8. Pituitary (Hypophysis) Thyroid Parathyroid Adrenal or Supra-Renal Pancreas Gonads Pineal Thymus

 Pituitary gland – two-lobed organ that secretes nine major hormones  About the size and shape of a Pea or Almond  Lies in the sella turcica, a bony cavity at the base of the brain  In humans, the pituitary gland has two major lobes  Posterior Pituitary Lobe  Anterior Pituitary Lobe  Posterior lobe – Neurohypophysis (neural tissue) and the infundibulum (funnel shaped connecting stalk)  Receives, stores, and releases hormones from the hypothalamus  Anterior lobe – Adenohypophysis made up of glandular tissue  Synthesizes and secretes a number of hormones

Major Endocrine Organs: Pituitary (Hypophysis)

Major Endocrine Organs: Pituitary (Hypophysis)

   

Pituitary-Hypothalamic Relationships: Posterior Lobe The posterior lobe is a down growth of hypothalamic neural tissue Connected to hypothalamus through nerve bundle callled (hypothalamic-hypophyseal tract) This tract arises from neurons in the supraoptic and paraventricular nuclei of the hypothalamus Nuclei of the hypothalamus synthesize two hormones  ADH (supraoptic)  Oxytocin (paraventricular) These hormones are transported to the posterior pituitary  Stored hormones are released in general circulation when hypothalamic neurons fire.

Pituitary-Hypothalamic Relationships: Anterior Lobe

  The glandular anterior lobe originates from a superior out pocketing of the oral mucosa and is formed from epithelial tissue  There is no direct neural contact with the hypothalamus but there is a vascular connection  This vascular connection, the hypophyseal portal system, consists of:  The primary capillary plexus (in infundibulum)  The hypophyseal portal veins  The secondary capillary plexus (in anterior lobe)
PLAY InterActive Physiology®: Endocrine System: The Hypothalamic-Pituitary Axis

Major Endocrine Organs: Pituitary ( Hypophysis)

Adenophypophyseal Hormones
 The six hormones of the adenohypophysis, all of them proteins,  Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL  Regulate the activity of other endocrine glands  In addition, pro-opiomelanocortin (POMC) has been isolated from the pituitary  POMC is a prohormone, can split enzymatically into one or more active hormones.  POMC is the source of  Adrenocorticotropic hormone,  Two natural opiates Enkephalin and Beta endorphin  Melanocyte-stimulating hormone (MSH).  In Animals MSH melanocytes  melanin pigment synthesis  In humans, MSH is a CNS neurotransmitter that controls appetite.

Adenophypophyseal Hormones
Hypothalamu s Hormones
GHIH GHRH CRH TRH

Secreting Cells
Somatotroph (30-40%) Corticotroph Thyrotroph

Hormone
Growth Hormone (GH) Adrenocorticotropi c Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Follicle stimulating Hormone (FSH) Luteinizing Hormone (LH) Prolactin (PRL)

Chemical Nature
Protein (Single chain 191 AA) Polypeptide (Single chain 39 AA)
( α-89 amino acids) (ß-112 amino acids) ( α-89 amino acids) (ß-112 amino acids) ( α-89 amino acids) (ß-115 amino acids) Protein (Single chain 198 AA)

Glycoprotein

GnRH GnRH

Gonadotroph

Glycoprotein

Gonadotroph

Glycoprotein

PIH

Lactotroph

Activity of the Adenophypophysis

 The hypothalamus sends a chemical stimulus to the anterior pituitary  Releasing hormones stimulate the synthesis and release of hormones  Inhibiting hormones shut off the synthesis and release of hormones

Hypothalamic Releasing and Inhibitory Hormones That Control Secretion of the Anterior Pituitary Gland
Hormone Thyrotropin-releasing hormone (TRH) Gonadotropin-releasing hormone (GnRH) Corticotropin-releasing hormone (CRH) Growth hormone releasing hormone (GHRH) Growth hormone inhibitory hormone (GHIH) Prolactin-inhibiting hormone (PIH) Chemical Nature Peptide of 3 amino acids Single chain of 10 amino acids Single chain of 41 amino acids Single chain of 44 amino acids Single chain of 14 amino acids Dopamine (a catecholamine) Primary Action on Anterior Pituitary Stimulates secretion of TSH by thyrotropes Stimulates secretion of FSH and LH by gonadotropes Stimulates secretion of ACTH by corticotropes Stimulates secretion of growth hormone by somatotropes Inhibits secretion of growth hormone by somatotropes Inhibits secretion of prolactin by lactotropes

Growth Hormone (GH)
 Growth hormone (GH) is produced by cells called somatotrophs of the anterior lobe.  It is a 191-amino acid, single-chain protein hormone  GH stimulates most body cells to increase in size and divide, its major targets are  Bones & Skeletal muscles.  Stimulation of the epiphyseal plate leads to long bone growth  Stimulation of skeletal muscles promotes increased muscle mass.  Essentially an anabolic (tissue-building) hormone that,  Promotes protein synthesis,  Encourages the use of fats for fuel,  Conserves glucose

Growth Hormone (GH) Metabolic Actions  Indirect Actions:  Most effects are mediated indirectly by insulin-like growth factors (IGFs) or somatomedins.  These are a family of growth-promoting proteins produced by  The liver,  Skeletal muscle,  Bone, and other tissues.  IGFs Specifically,  Stimulate uptake of amino acids from the blood for cellular proteins synthesis  Stimulate uptake of sulfur into cartilage matrix  (Needed for the synthesis of chondroitin

Growth Hormone (GH) Metabolic Actions
 Direct Actions  GH mobilizes fats from fat depots for transport to cells, increasing blood levels of fatty acids.  It decreases the rate of glucose uptake and metabolism.  In the liver, it encourages glycogen breakdown and release of glucose to the blood.  Diabetogenic effect of GH due to glucose sparing  Regulation of GH release  Antagonistic hypothalamic hormones regulate GH  Growth hormone–releasing hormone (GHRH) stimulates GH release  Growth hormone–inhibiting hormone (GHIH) inhibits GH release

Metabolic Action of Growth Hormone

Figure 16.6

Gigantism & Acromegaly
 Hypersecretion in children results in gigantism  The person becomes abnormally tall, often reaching a height of 2.4 m (8 feet), but has relatively normal body proportions.  Acromegaly literally translated as “enlarged extremities,”  If excessive amounts of GH are secreted after the epiphyseal plates have closed,  This condition is characterized by overgrowth of bony areas still responsive to GH, namely bones of the hands, feet, and face.  Hypersecretion usually results from an adenohypophyseal tumor that releases excessive amounts of GH  Usual treatment is surgical removal of the tumor  Anatomical changes that have already occurred are not reversible.

Dwarfism
 Hyposecretion of GH in adults usually causes no problems.  GH deficiency in children results in slowed long bone growth, a condition called pituitary dwarfism.  Such individuals attain a maximum height of 1.2 m (4 feet), but usually have fairly normal body proportions.  Lack of GH is often accompanied by deficiencies of other adenohypophyseal hormones, and if thyroidstimulating hormone and gonadotropins are lacking, the individual will be malproportioned and will fail to mature sexually as well.  Treatment  When pituitary dwarfism is diagnosed before puberty, growth hormone replacement therapy can promote nearly normal somatic growth.

Gigantism & Acromegaly

Thyroid Stimulating Hormone (Thyrotropin)

 Tropic hormone that stimulates the normal development and secretory activity of the thyroid gland  Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH)  Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH

Adrenocorticotropic Hormone (Corticotropin)

 Stimulates the adrenal cortex to release corticosteroids  Triggered by hypothalamic corticotropinreleasing hormone (CRH) in a daily rhythm  Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH

Gonadotropins

 Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH)  Regulate the function of the ovaries and testes  FSH stimulates gamete (egg or sperm) production  Absent from the blood in prepubertal boys and girls  Triggered by the hypothalamic gonadotropinreleasing hormone (GnRH) during and after puberty

Functions of Gonadotropins

 In females  LH works with FSH to cause maturation of the ovarian follicle  LH works alone to trigger ovulation (expulsion of the egg from the follicle)  LH promotes synthesis and release of estrogens and progesterone

Functions of Gonadotropins

 In males  LH stimulates interstitial cells of the testes to produce testosterone  LH is also referred to as interstitial cellstimulating hormone (ICSH) in males.

Prolactin (PRL)

 In females, stimulates milk production by the breasts  Triggered by the hypothalamic prolactin-releasing hormone (PRH)  Inhibited by prolactin-inhibiting hormone (PIH)  Blood levels rise toward the end of pregnancy  Suckling stimulates PRH release and encourages continued milk production  In females, prolactin levels rise and fall in rhythm with estrogen blood levels.  Estrogen stimulates prolactin release, both directly and indirectly.

The Posterior Pituitary and Hypothalamic Hormones

 Posterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hormone (ADH) and oxytocin  ADH and oxytocin are synthesized in the hypothalamus  ADH influences water balance  Oxytocin stimulates smooth muscle contraction in breasts and uterus  Both use PIP-calcium second-messenger mechanism

Oxytocin

 Oxytocin is a strong stimulant of uterine contraction  Regulated by a positive feedback mechanism to oxytocin in the blood  This leads to increased intensity of uterine contractions, ending in birth  Oxytocin triggers milk ejection (“letdown” reflex) in women producing milk  Synthetic and natural oxytocic drugs are used to induce or hasten labor  Plays a role in sexual arousal and satisfaction in males and nonlactating females

Antidiuretic Hormone (ADH)

 ADH helps to avoid dehydration or water overload  Prevents urine formation  Osmoreceptors monitor the solute concentration of the blood  With high solutes, ADH is synthesized and released, thus preserving water  With low solutes, ADH is not released, thus causing water loss from the body  Alcohol inhibits ADH release and causes copious urine output

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