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Basic Physiology - Unit 02 Part 01 by Cool Education Nursing Academy

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Basic Physiology

Unit 02 (Part o1)

Hormones:
• (Introduction, classification, mechanism of action, biological functions of thyroid,
parathyroid, pituitary, adrenal, gonadal and pancreatic hormones)

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Introduction to Endocrinology

Coordination of Body Functions by Chemical Messengers

Chemical Messenger Systems in the Body

The body uses different types of chemical messenger systems to coordinate the activities
of cells, tissues, and organs. These systems are crucial for maintaining body functions and
overall balance.

Neurotransmitters

• Released by neuron axon terminals.


• Act locally within synaptic junctions to control nerve cell functions.
• Play a key role in the nervous system's rapid communication.

Endocrine Hormones

• Produced by glands or specialized cells.

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• Released into the bloodstream to affect target cells in other parts of the body.
• Influence a wide range of processes, including metabolism, growth, and energy
use.

Neuroendocrine Hormones

• Secreted by neurons but travel through the blood.


• Target cells far from their origin, similar to endocrine hormones.
• Control key functions, like stress response, through hormones like oxytocin and
ADH.

Paracrines

• Secreted into the extracellular fluid by cells.


• Influence neighboring cells of a different type.
• Function within a localized area for rapid cell-to-cell communication.

Autocrines

• Released by cells into the extracellular fluid.


• Affect the same cells that produced them, leading to self-regulation.
• Important in processes like cell growth and immune response.

Cytokines

• Peptides secreted into the extracellular fluid.


• Function as autocrines, paracrines, or endocrine hormones.
• Include immune-related chemicals like interleukins and adipokines like leptin.

Interplay Between Hormone Systems

• The body’s chemical messenger systems work together to maintain stability


(homeostasis).
• The adrenal medullae and pituitary gland respond to neural stimuli, while the
hypothalamus influences hormone release in the pituitary.
• Hormones travel through the circulatory system to interact with specific receptors,
leading to a variety of effects.

Target Cells and Specific Hormonal Effects

• Some hormones have widespread effects. For example, growth hormone promotes
body growth, while thyroxine from the thyroid boosts chemical reactions in most
cells.
• Others are more specific. ACTH, from the anterior pituitary, targets the adrenal
cortex. Ovarian hormones focus on female reproductive organs and secondary
characteristics.

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Importance of Hormones in Body


Functions

• Hormones regulate metabolism,


growth, development, water balance,
reproduction, and behavior.
• Deficiencies in key hormones can lead
to significant health impacts:
o Lack of growth hormone leads
to stunted growth.
o Thyroid hormone deficiency
slows chemical reactions,
causing fatigue.
o Without insulin, cells can't
effectively use carbohydrates
for energy.
o Absence of sex hormones halts
sexual development and
reproductive functions.

Overview of Endocrine System

• The major endocrine glands are


distributed throughout the body, each
playing a unique role.
• These glands, along with specialized
tissues, regulate essential bodily
processes to maintain overall health.

Anatomical loci of the principal endocrine

glands and tissues of the body

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Classification of Hormones
The body has three main classes of hormones, each serving different roles in regulating
bodily functions:

1. Proteins and Polypeptides

• These include hormones made up of amino acid chains.


• Examples: Insulin and glucagon from the pancreas, growth hormone from the
pituitary, and parathyroid hormone.
• Sources: Secreted by the anterior and posterior pituitary, pancreas, parathyroid
gland, and others.
• They regulate many functions, from metabolism to growth.

2. Steroids

• Derived from cholesterol and are lipid-based hormones.


• Examples: Cortisol and aldosterone from the adrenal cortex; estrogen and
progesterone from the ovaries and placenta; testosterone from the testes.
• Sources: Produced by the adrenal cortex, ovaries, testes, and placenta.
• They mainly affect reproductive functions, stress responses, and electrolyte
balance.

3. Amino Acid Derivatives

• Hormones formed from modifications of amino acids, specifically tyrosine.


• Examples: Thyroxine and triiodothyronine from the thyroid, and epinephrine
and norepinephrine from the adrenal medulla.
• Sources: Secreted by the thyroid and adrenal medullae.
• They play a significant role in regulating metabolism, stress response, and energy
levels.

Note

• There are no known hormones made from polysaccharides or nucleic acids.


Hormones are typically based on proteins, steroids, or modified amino acids for
efficient communication within the body.

Storage and Release of Polypeptide and Protein Hormones

Most hormones in the body fall under the category of polypeptides and proteins. They
vary significantly in size and are stored until needed.

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Types of Polypeptide and Protein Hormones

• Hormones can range from small peptides (like thyrotropin-releasing hormone


with 3 amino acids) to larger proteins (like growth hormone and prolactin, with
nearly 200 amino acids).
• Hormones with 100 or more amino acids are considered proteins, while those
with fewer than 100 amino acids are referred to as peptides.

Synthesis of Hormones

• These hormones are synthesized on the rough endoplasmic reticulum of endocrine


cells.
• Initial synthesis creates larger, inactive proteins called preprohormones.
• Preprohormones are converted to smaller prohormones in the endoplasmic
reticulum.
• Prohormones are then packaged into secretory vesicles in the Golgi apparatus.
• Within the vesicles, enzymes modify prohormones into active hormones and
some inactive fragments.

Storage and Secretion Process

• Secretory vesicles are stored in the cell’s cytoplasm, often near the cell membrane.
• These vesicles remain there until a signal triggers their release.
• When the hormone is needed, vesicles fuse with the cell membrane,
releasing their contents into the blood or surrounding fluids via exocytosis.

Triggers for Hormone Release

• An increase in cytosolic calcium due to plasma membrane depolarization often


triggers exocytosis.
• In other cases, stimulation of cell surface receptors can increase cAMP levels,
activating protein kinases that prompt hormone release.

Characteristics of Peptide Hormones

• Peptide hormones are water-soluble, allowing easy entry into the circulatory
system.
• This water solubility facilitates their transport to target tissues throughout the
body, ensuring efficient communication for bodily functions.

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Synthesis and secretion of peptide hormones. The stimulus for hormone secretion often involves changes
in intracellular calcium or changes in cyclic adenosine monophosphate (cAMP) in the cell.

Steroid and Amine Hormones: Synthesis and Storage


The synthesis, storage, and release of steroid and amine hormones differ significantly due
to their chemical structures and functions.
Steroid Hormones
• Source: Synthesized from cholesterol, sharing a similar chemical structure.
• Structure: Composed of three cyclohexyl rings and one cyclopentyl ring.
• Storage: Minimal hormone storage in cells; instead, large amounts of cholesterol
esters are kept in cytoplasmic vacuoles for quick mobilization when needed.
• Synthesis Process:
o Cholesterol is sourced from the plasma or synthesized within steroid-
producing cells.
o Upon a stimulus, cholesterol is converted into steroid hormones.
o Due to their lipid-soluble nature, they diffuse directly through the cell
membrane into the interstitial fluid and enter the bloodstream.

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Amine Hormones
• Source: Derived from the amino acid tyrosine, with two main groups—thyroid
hormones and adrenal medullary hormones.
• Synthesis in Thyroid:
o Thyroid hormones are created in the thyroid gland and stored within a
protein called thyroglobulin in gland follicles.
o When needed, thyroid hormones are released from thyroglobulin, enter the
bloodstream, and bind to plasma proteins like thyroxine-binding globulin
for transport.
• Synthesis in Adrenal Medulla:
o Epinephrine and norepinephrine (catecholamines) are synthesized in the
adrenal medulla.
o These hormones are stored in vesicles and released by exocytosis upon
stimulation.
o The adrenal medulla secretes more epinephrine than norepinephrine, about
a 4:1 ratio.
Hormone Release and Transport
• Steroid Hormones: Highly lipid-soluble, diffusing freely across cell membranes
and entering circulation immediately after synthesis.
• Amine Hormones:
o Thyroid Hormones: Stored in the gland until split from thyroglobulin,
then released into the bloodstream where they bind to transport proteins
for gradual delivery to target tissues.
o Catecholamines: Stored in preformed vesicles and released by exocytosis
into circulation, where they may remain free or conjugate with other
substances.
Understanding the synthesis and storage methods of these hormones highlights the
body's intricate systems for regulating vital functions, from stress responses to
metabolism and energy balance.

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Endocrine Glands, Hormones, and Their Functions and


Structure
Chemical
Gland/Tissue Hormones Major Functions
Structure
Stimulates secretion of thyroid-
Thyrotropin-releasing
Hypothalamus stimulating hormone (TSH) and Peptide
hormone (TRH)
prolactin

Corticotropin-releasing Causes release of adrenocorticotropic


Peptide
hormone (CRH) hormone (ACTH)

Growth hormone–releasing
Causes release of growth hormone Peptide
hormone (GHRH)

Growth hormone inhibitory


hormone (GHIH) Inhibits release of growth hormone Peptide
(somatostatin)

Causes release of luteinizing hormone


Gonadotropin-releasing
(LH) and follicle-stimulating hormone Peptide
hormone (GnRH)
(FSH)

Dopamine or prolactin-
Inhibits release of prolactin Amine
inhibiting factor (PIF)

Anterior Stimulates protein synthesis and


Growth hormone Peptide
pituitary overall growth of most cells and tissues

Stimulates synthesis and secretion of


TSH thyroid hormones (thyroxine and Peptide
triiodothyronine)

Stimulates synthesis and secretion of


ACTH adrenocortical hormones (cortisol, Peptide
androgens, and aldosterone)

Promotes development of the female


Prolactin Peptide
breasts and secretion of milk

Causes growth of follicles in the ovaries


FSH and sperm maturation in Sertoli cells Peptide
of testes

Stimulates testosterone synthesis in


Leydig cells of testes; stimulates
LH ovulation, formation of corpus luteum, Peptide
and estrogen and progesterone
synthesis in ovaries

Increases water reabsorption by the


Posterior Antidiuretic hormone (ADH)
kidneys and causes vasoconstriction Peptide
pituitary (vasopressin)
and increased blood pressure

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Stimulates milk ejection from breasts


Oxytocin Peptide
and uterine contractions

Increases the rates of chemical


Thyroxine (T4) and
Thyroid reactions in most cells, thus increasing Amine
triiodothyronine (T3)
body metabolic rate

Promotes deposition of calcium in the


Calcitonin bones and decreases extracellular fluid Peptide
calcium ion concentration

Has multiple metabolic functions for


Adrenal controlling metabolism of proteins,
Cortisol Steroid
cortex carbohydrates, and fats; also has anti-
inflammatory effects

Increases renal sodium reabsorption,


Aldosterone potassium secretion, and hydrogen ion Steroid
secretion

Adrenal Norepinephrine, Same effects as sympathetic


Amine
medulla epinephrine stimulation

Promotes glucose entry in many cells,


Pancreas Insulin (β cells) and in this way controls carbohydrate Peptide
metabolism

Increases synthesis and release of


Glucagon (α cells) glucose from the liver into the body Peptide
fluids

Controls serum calcium ion


concentration by increasing calcium
Parathyroid Parathyroid hormone (PTH) Peptide
absorption by the gut and kidneys and
releasing calcium from bones

Promotes development of male


Testes Testosterone reproductive system and male Steroid
secondary sexual characteristics

Promotes growth and development of


female reproductive system, female
Ovaries Estrogens Steroid
breasts, and female secondary sexual
characteristics

Stimulates secretion of "uterine milk"


by the uterine endometrial glands and
Progesterone Steroid
promotes development of secretory
apparatus of breasts

Promotes growth of corpus luteum and


Human chorionic
Placenta secretion of estrogens and Peptide
gonadotropin (HCG)
progesterone by corpus luteum

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Probably helps promote development


Human
of some fetal tissues as well as the Peptide
somatomammotropin
mother’s breasts

Estrogens See actions of estrogens from ovaries Steroid

See actions of progesterone from


Progesterone Steroid
ovaries

Catalyzes conversion of
Kidney Renin angiotensinogen to angiotensin I (acts Peptide
as an enzyme)

1,25- Increases intestinal absorption of


Steroid
Dihydroxycholecalciferol calcium and bone mineralization

Erythropoietin Increases erythrocyte production Peptide

Atrial natriuretic peptide Increases sodium excretion by kidneys,


Heart Peptide
(ANP) reduces blood pressure

Stimulates HCl secretion by parietal


Stomach Gastrin Peptide
cells

Small Stimulates pancreatic acinar cells to


Secretin Peptide
intestine release bicarbonate and water

Stimulates gallbladder contraction and


Cholecystokinin (CCK) Peptide
release of pancreatic enzymes

Inhibits appetite, stimulates


Adipocytes Leptin Peptide
thermogenesis

Hormone Secretion, Transport, and Clearance from the Blood


Hormone Secretion, Transport, and Clearance
Hormones play a crucial role in controlling body functions, and understanding their
secretion, transport, and clearance is essential to grasp how they regulate various systems.
Onset of Hormone Secretion and Duration of Action
• Hormones like norepinephrine and epinephrine act quickly, developing full
effects within seconds to minutes after release.
• In contrast, hormones like thyroxine and growth hormone can take months
for their full impact.
• Each hormone’s timing is tailored to its specific function, providing precise control
over different physiological processes.

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Hormone Concentrations and Secretion Rates


• Hormones are effective even in tiny concentrations, ranging from picograms to
micrograms per milliliter of blood.
• The secretion rates of hormones are equally small, often in micrograms or
milligrams per day.
• Despite their minute amounts, hormones have powerful effects due to specialized
mechanisms in target tissues.
Feedback Control of Hormone Secretion
• Negative Feedback is the primary mechanism that prevents overactivity. It
limits hormone production once desired levels are reached.
o Example: Hormone action leads to conditions that reduce further secretion,
maintaining balance.
• Positive Feedback occurs less frequently but can amplify hormone release.
o Example: Before ovulation, estrogen stimulates the release of luteinizing
hormone (LH), which in turn increases estrogen, creating a cycle that halts
once LH reaches the required level.
• Hormone secretion can also show cyclical variations, influenced by factors like
seasons, age, daily rhythms, and sleep cycles.
Transport of Hormones in the Blood
• Water-soluble hormones (like peptides and catecholamines) dissolve in
plasma, travel through blood, and diffuse to target cells.
• Lipid-soluble hormones (like steroid and thyroid hormones) mostly bind to
plasma proteins, acting as a reservoir.
o Bound hormones are biologically inactive until they dissociate from plasma
proteins, allowing slow and sustained effects.
Hormone Clearance from the Blood
• Hormone levels depend on secretion rates and the metabolic clearance rate,
which measures how quickly hormones are removed from the blood.
o This is calculated by dividing the disappearance rate by the hormone's
plasma concentration.
• Methods of Hormone Clearance:
o Metabolic destruction by tissues.
o Binding to tissues.

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o Excretion by the liver into bile.


o Excretion by the kidneys into urine.
• Hormones have different half-lives:
o Peptide hormones and catecholamines are short-lived, lasting minutes
due to quick enzymatic breakdown and kidney/liver excretion.
o Protein-bound hormones have longer lifespans, from several minutes
to days, due to slower clearance.

Mechanisms of Action of Hormones


Hormone Receptors and Their Activation
The effectiveness of hormones relies heavily on their interaction with specific receptors
located in target cells. These interactions initiate a series of cellular responses.
Binding to Specific Receptors
• Hormones must bind to specific receptors on target cells to initiate a response.
• Cells without receptors for a hormone will not respond, ensuring that hormone
effects are limited to appropriate tissues.
• Receptors can be found in three locations:
1. Cell Membrane: For protein, peptide, and catecholamine hormones.
2. Cytoplasm: Mainly for steroid hormones.
3. Nucleus: For thyroid hormones, often associated with chromosomes.
Receptor Specificity and Target Tissues
• Each hormone receptor is highly specific, allowing only particular hormones to
interact with it.
• A cell usually contains between 2,000 to 100,000 receptors, influencing how
responsive it is to hormone signals.
• Specificity determines which tissues are affected by a hormone, as only cells with
matching receptors will respond.
Regulation of Receptor Numbers and Sensitivity
• The number of receptors on a cell is not static; it can change rapidly depending on
hormone levels and cell conditions.
• Down-Regulation occurs when receptor numbers decrease, reducing sensitivity
to a hormone. This can result from:

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1. Inactivation of receptors or signaling molecules.


2. Receptors moving away from the cell surface.
3. Destruction of receptors after they are internalized.
4. Reduced production of new receptors.
• Up-Regulation leads to an increase in receptor numbers or intracellular
signaling molecules, making the target cell more sensitive to hormones.
1. This enhancement can make the tissue respond more strongly to lower
hormone concentrations.
Amplification of Hormone Effects
• Once a hormone binds to its receptor, it triggers a cascade of reactions inside
the cell.
• Each stage in this cascade amplifies the initial signal, allowing even small hormone
amounts to produce significant cellular effects.

Intracellular Signaling After Hormone Receptor Activation


Hormone-Receptor Complex and Activation
Hormones exert their influence by forming a hormone-receptor complex, which modifies
the receptor's function to trigger specific cellular responses. Different types of
interactions between hormones and receptors drive these responses.
Ion Channel–Linked Receptors
• Many neurotransmitters like acetylcholine and norepinephrine use ion
channel-linked receptors.
• Binding to the receptor causes a change in the receptor's structure, leading to the
opening or closing of ion channels.
o Examples include channels for sodium, potassium, or calcium ions.
• This altered ion movement affects the postsynaptic cells, leading to various
cellular responses.
• While some hormones directly use ion channel-linked receptors, most utilize them
indirectly through more complex pathways.
G Protein–Linked Hormone Receptors
• A major pathway involves G protein–linked receptors, which indirectly affect
target proteins.
• These receptors have seven transmembrane segments that interact with G
proteins in the cell's membrane.

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o G proteins consist of three subunits: α, β, and γ.


• When a hormone (ligand) binds to the receptor, it causes a conformational
change, activating the G protein.
Activation and Signal Transmission
• In the inactive state, the G protein binds guanosine diphosphate (GDP) on the α
subunit.
• Upon receptor activation:
o The G protein exchanges GDP for guanosine triphosphate (GTP),
causing the α subunit to separate from the β and γ subunits.
o The α subunit interacts with intracellular signaling proteins, altering ion
channels or enzyme activity (like adenylyl cyclase or phospholipase C).
Signal Termination and Regulation
• The signal ends when the hormone is removed, and the α subunit converts GTP
back to GDP, recombining with the β and γ subunits to return to its inactive state.
• Some hormones use inhibitory G proteins (Gi), while others use stimulatory
G proteins (Gs), allowing for diverse responses.
o Inhibitory G proteins decrease the activity of intracellular enzymes,
while stimulatory G proteins increase it.
This complex G protein system enables cells to respond precisely and variably to different
hormones, depending on the target tissue's needs, creating a highly adaptable signaling
network within the body.

Mechanism of activation of a G protein–coupled receptor. When the hormone activates the receptor, the inactive α,
β, and γ G protein complex associates with the receptor and is activated, with an exchange of guanosine triphosphate
(GTP) for guanosine diphosphate (GDP). This causes the α subunit (to which the GTP is bound) to dissociate from the
β and γ subunits of the G protein and to interact with membrane-bound target proteins (enzymes) that initiate
intracellular signals.

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Enzyme-Linked Hormone Receptors


Enzyme-linked hormone receptors play a significant role in cellular signaling by directly
or indirectly activating enzymes. These receptors are distinct from G protein-coupled
receptors and have unique mechanisms for transmitting hormone signals.
Structure and Function
• Enzyme-linked receptors cross the membrane only once, unlike the seven-
segment G protein-coupled receptors.
• They have two main components:
o The hormone-binding site is located outside the cell membrane.
o The catalytic or enzyme-binding site is inside the membrane.
• When a hormone binds to the receptor’s external part, an enzyme inside the
membrane is activated, triggering intracellular effects.
Example: Leptin Receptor
• The leptin receptor is part of the cytokine receptor family and does not have its
own enzymatic activity.
• It signals through associated enzymes like tyrosine kinase, specifically the JAK
family (e.g., JAK2).
o Leptin binding changes the receptor's shape, allowing JAK2
phosphorylation.
o Phosphorylated JAK2 activates intracellular signaling, leading to gene
transcription and protein synthesis.
o Signals include the activation of pathways like MAPK and PI3K.
Rapid and Slow Actions of Leptin
• Some effects, like enzyme activation, occur quickly.
• Others require protein synthesis, which happens gradually as the target genes
are transcribed.
cAMP as a Second Messenger
• Some hormones use special transmembrane receptors that activate adenylyl
cyclase inside the cell.
o Adenylyl cyclase catalyzes the creation of cyclic adenosine
monophosphate (cAMP).
o cAMP acts as a second messenger, conveying intracellular signals to
regulate cell functions.

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• cAMP is not the hormone itself but carries out hormone instructions inside the
cell, affecting various pathways.
cGMP as a Second Messenger
• For specific hormones like atrial natriuretic peptide (ANP), cyclic
guanosine monophosphate (cGMP) acts similarly to cAMP.
o It also functions as a second messenger, influencing intracellular processes.
Enzyme-linked receptors provide diverse ways for hormones to regulate cellular
activities, enabling precise and varied responses depending on the target cell’s needs.

An enzyme-linked receptor—the leptin receptor. The receptor exists as a homodimer (two identical parts), and leptin
binds to the extracellular part of the receptor, causing phosphorylation and activation of the intracellular associated
Janus kinase 2 (JAK2). This causes phosphorylation of signal transducer and activator of transcription (STAT)
proteins, which then activates the transcription of target genes and the synthesis of proteins. JAK2 phosphorylation
also activates several other enzyme systems that mediate some of the more rapid effects of leptin.

Intracellular Hormone Receptors and Gene Activation

Certain hormones operate inside the cell, utilizing intracellular receptors to influence
gene activity. These hormones are typically lipid-soluble, allowing them to cross the cell
membrane easily.

Hormones Using Intracellular Receptors

• Examples: Adrenal and gonadal steroids, thyroid hormones, retinoid hormones,


and vitamin D.

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• These hormones bypass membrane-bound receptors, interacting directly with


receptors located in the cytoplasm or nucleus.

Activation of Gene Transcription

• Once inside the cell, the hormone binds to a specific intracellular receptor,
forming a hormone-receptor complex.
• This complex binds to a regulatory DNA sequence known as the hormone
response element.
o This binding either activates or represses gene transcription, leading
to the production of messenger RNA (mRNA).
o The mRNA directs the synthesis of new proteins that control altered cellular
functions.
• The process can take minutes to days, depending on the hormone and cellular
environment.

Tissue-Specific Responses

• Many tissues have identical intracellular receptors, but their responses vary.
o The same receptor may regulate different genes in different tissues.
• This variation is due to the presence of tissue-specific gene regulatory
proteins.
o A gene response will only be activated if the correct combination of
regulatory proteins is present, which is unique to each tissue.

Impact on Cellular Functions

• New proteins created through this process lead to new or modified cellular
activities, demonstrating how hormones can precisely influence cell behavior
over time.
• The specificity of hormonal effects is determined by both the receptor's presence
and the genes that it regulates in different tissues.

Intracellular hormone receptors provide a pathway for hormones to exert long-lasting


changes by directly influencing gene expression, tailoring the body's responses to specific
conditions and environments.

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echanisms of interaction of lipophilic hormones, such as steroids, with intracellular receptors in target cells. After the
hormone binds to the receptor in the cytoplasm or in the nucleus, the hormone-receptor complex binds to the hormone
response element (promoter) on the DNA. This either activates or inhibits gene transcription, formation of messenger
RNA (mRNA), and protein synthesis.

Other Mechanism’s
Second Messenger Mechanisms for Intracellular Hormonal Functions
Hormones often rely on second messengers to transmit their effects within cells. These
second messengers amplify and mediate the hormone's influence after it binds to its
receptor.
Role of Second Messengers
• A hormone's primary action is to activate a specific membrane receptor.
• This receptor activation leads to the formation of a second messenger, which
carries out the hormone's effects inside the cell.
• Second messengers enable a small hormone signal to cause a significant impact
through amplification.
Key Second Messengers
1. Cyclic Adenosine Monophosphate (cAMP)
o cAMP is one of the most common second messengers.
o After hormone-receptor binding, cAMP is formed inside the cell membrane.
o It triggers various intracellular actions, depending on the target tissue.
2. Calcium Ions and Calmodulin
o Calcium ions act as another second messenger.

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o When calcium levels increase within the cell, calcium binds to a protein
called calmodulin.
o The calcium-calmodulin complex activates various enzymes, leading to the
desired hormonal effect.
3. Products of Membrane Phospholipid Breakdown
o Hormone binding can lead to the breakdown of cell membrane
phospholipids.
o This process generates second messengers like diacylglycerol (DAG) and
inositol triphosphate (IP3).
o These molecules regulate processes like calcium release and protein
activation, further amplifying the hormone's effect.
Amplification of Hormonal Signals
• Each second messenger activates a cascade of intracellular reactions,
allowing even a small amount of hormone to produce significant changes.
• This system enables hormones to have specific and targeted effects while
using minimal direct interaction with the cell.

Hormones That Use the Adenylyl Cyclase–cAMP Second Messenger System


Hormone Receptor/Cell Type
Adrenocorticotropic hormone (ACTH) ACTH receptor
Angiotensin II Epithelial cells
Calcitonin Calcitonin receptor
Catecholamines β receptors
Corticotropin-releasing hormone (CRH) CRH receptor
Follicle-stimulating hormone (FSH) FSH receptor
Glucagon Glucagon receptor
Human chorionic gonadotropin (HCG) LH/CG receptor
Luteinizing hormone (LH) LH receptor
Parathyroid hormone (PTH) PTH receptor
Secretin Secretin receptor
Somatostatin Somatostatin receptor
Thyroid-stimulating hormone (TSH) TSH receptor
Vasopressin V2 receptor, epithelial cells

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Adenylyl Cyclase–cAMP Second Messenger System

The adenylyl cyclase-cAMP mechanism is a crucial pathway that many hormones use to
influence target cells, leading to diverse cellular responses through the activation or
inhibition of specific enzymes.

How the cAMP System Works

• Hormones bind to specific receptors on the cell membrane, which then couple
with G proteins.
o If the G protein is a Gs protein (stimulatory), it activates the adenylyl
cyclase-cAMP pathway.
o If the G protein is a Gi protein (inhibitory), it suppresses this pathway.

Activation of cAMP Pathway

1. Hormone binding to the receptor allows it to interact with the Gs protein.


2. The Gs protein stimulates adenylyl cyclase, a membrane-bound enzyme.
3. Adenylyl cyclase converts ATP (adenosine triphosphate) into cAMP (cyclic
adenosine monophosphate) inside the cell.
4. cAMP activates cAMP-dependent protein kinase, leading to the
phosphorylation of specific proteins.
5. This phosphorylation triggers a series of biochemical reactions, resulting in the
cell’s specific response.

Cascade Amplification Effect

• The cAMP pathway triggers a cascade of enzyme activation, amplifying the


original hormonal signal.
o A few activated molecules of adenylyl cyclase can activate numerous
downstream enzymes, creating a powerful cascading effect.
• This amplification allows even a small hormonal stimulus to produce significant
changes in cell function.

Inhibitory cAMP Pathway

• When hormones interact with a Gi protein, adenylyl cyclase activity is inhibited.


o This reduces cAMP formation and leads to inhibitory actions within the
cell, depending on the cell type.

Cell-Specific Responses to cAMP

• The effects of cAMP differ based on the target cell's intracellular machinery,
leading to various outcomes:
o Thyroid cells produce metabolic hormones like thyroxine.
o Adrenocortical cells secrete steroid hormones.
o Renal tubular epithelial cells increase their permeability to water.

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cAMP’s role as a versatile second messenger enables hormones to exert precise control
over a wide range of cellular processes, adapting to the unique needs of different tissues.

Cyclic adenosine monophosphate (cAMP) mechanism by which many hormones exert their control of
cell function. ADP, adenosine diphosphate; ATP, adenosine triphosphate.

Cell Membrane Phospholipid Second Messenger System

The phospholipid second messenger system is another critical pathway that hormones
use to influence cellular processes. It relies on the breakdown of cell membrane
phospholipids to create multiple second messengers, leading to diverse cellular effects.

Hormones That Use the Phospholipase C Second Messenger System

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Activation of the Phospholipid Pathway

• Hormones bind to transmembrane receptors, which activate the enzyme


phospholipase C inside the cell membrane.
• Phospholipase C breaks down a specific phospholipid, phosphatidylinositol
bisphosphate (PIP2), into two second messengers:
1. Inositol Triphosphate (IP3)
2. Diacylglycerol (DAG)

Role of Inositol Triphosphate (IP3)

• IP3 mobilizes calcium ions from the mitochondria and the endoplasmic
reticulum.
• Released calcium ions act as a second messenger, leading to effects like:
o Smooth muscle contraction
o Altered cell secretion

Role of Diacylglycerol (DAG)

• DAG activates protein kinase C (PKC), which phosphorylates various proteins.


o This phosphorylation leads to specific cellular responses based on the target
tissue.
• The lipid portion of DAG is arachidonic acid, a precursor for local hormones like
prostaglandins, which have widespread effects on tissues.

Summary of the Phospholipid Second Messenger System

• Hormones initiate this pathway by binding to specific cell surface receptors.


• The breakdown of PIP2 produces IP3 and DAG, each playing distinct roles in
influencing cellular activity.
o IP3 increases intracellular calcium levels, while DAG activates PKC and
contributes to the production of local hormones.

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The cell membrane phospholipid second messenger system by which some hormones exert their control
of cell function. DAG, diacylglycerol; IP3, inositol triphosphate; PIP2 , phosphatidylinositol biphosphate.

This system provides a versatile and multi-faceted approach to regulating cellular


functions, allowing hormones to have precise and targeted effects.

Calcium-Calmodulin Second Messenger System


The calcium-calmodulin system is a secondary pathway that uses calcium ions as
messengers to activate intracellular processes, allowing hormones to influence cell
functions.
How Calcium-Calmodulin System Works
1. Calcium Entry:
o Triggered by changes in membrane potential, which open calcium channels.
o Or initiated by hormones that bind to membrane receptors, leading to
calcium channel opening.
2. Binding to Calmodulin:
o Once inside the cell, calcium ions bind to the protein calmodulin, which
has four calcium-binding sites.

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o When three or four sites are occupied, calmodulin undergoes a shape


change, activating multiple intracellular effects.
3. Activation of Protein Kinases:
o Activated calmodulin triggers calmodulin-dependent protein
kinases, which modify proteins by phosphorylation.
o This phosphorylation can either activate or inhibit specific cellular
responses.
o Example: Calmodulin activates myosin light chain kinase, leading to
smooth muscle contraction.
Calcium Levels for Activation
• Normal intracellular calcium levels are 10⁻⁸ to 10⁻⁷ mol/L, not sufficient to
trigger calmodulin activity.
• A rise to 10⁻⁶ to 10⁻⁵ mol/L activates the calmodulin system, similar to calcium's
role in skeletal muscle contraction involving troponin C, which shares functional
and structural similarities with calmodulin.
Hormones That Act on Genetic Machinery
Some hormones, especially steroids and thyroid hormones, operate by influencing gene
expression, leading to long-term cellular changes.
Steroid Hormones and Protein Synthesis
• Steroid hormones from the adrenal cortex, ovaries, and testes stimulate the
production of new proteins in target cells.
• These proteins function as enzymes, transport proteins, or structural components,
affecting various cellular functions.
Sequence of Steroid Hormone Action
1. Diffusion: Steroid hormone crosses the cell membrane.
2. Binding: It binds to a specific receptor in the cytoplasm.
3. Nucleus Entry: The hormone-receptor complex moves to the nucleus and binds
to specific DNA regions.
4. Gene Activation: This activates gene transcription, forming mRNA.
5. Protein Synthesis: mRNA promotes new protein formation in the cytoplasm,
leading to altered cell function.
o Example: Aldosterone in renal cells enhances sodium reabsorption and
potassium secretion, taking 45 minutes to several days for full effects.

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Thyroid Hormones and Gene Transcription


• Thyroid hormones (thyroxine and triiodothyronine) bind directly to receptor
proteins in the cell nucleus.
• These hormones activate specific genes, leading to increased transcription and
protein production.
Key Features of Thyroid Hormone Function
1. Activation of genetic mechanisms produces numerous intracellular proteins, many
of which are enzymes that enhance metabolic activity.
2. Once bound, thyroid hormones can maintain their influence for days or even
weeks, allowing sustained cellular changes.

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