block 7- the endocrine system Flashcards
(104 cards)
1
Q
what is a gland
A
= collection of cells which make chemical messengers
2
Q
what are endocrine glands and their function
A
= Secrete hormones into the bloodstream
- hormones travel in blood to target organ where they have an effect
-specificity depends on receptor expression in target organs.
- consist of clumps of secretory epithelial cells surrounded by a vascular network.
Can be:
- part of epithelial surface such as lining of digestive tract
- separate organs such as thyroid or pituitary glands
3
Q
Exocrine vs. Endocrine Glands:
A
Exocrine: Ducts carry secretion to surface (e.g., sweat, saliva).
- has open contact with exterior
Endocrine: No ducts, internal secretion of hormones into blood.
- no contact with exterior
Some glands (e.g., pancreas) have both functions.
4
Q
what are the primary endocrine organs
secretes hormones
A
Hypothalamus & Pituitary (control centers).
Pineal gland (sleep cycle).
Thyroid gland (metabolism regulation).
parathyroid glands - controls calcium levels
-thymus
Adrenal glands (stress response, located on top of kidneys).
- pancreas - regulates blood sugar
- ovaries in females and testis in males
5
Q
secondary endocrine organs
A
Kidneys – Secretes erythropoietin (stimulates RBC production).
Liver – Produces angiotensinogen (blood pressure regulation).
Heart – Secretes ANP (Atrial Natriuretic Peptide, regulates blood pressure).
- role is to secrete hormones
6
Q
the pituitary gland
endocrine gland in the brain
A
Pituitary Gland (Hypophysis): Located in sphenoid bone; two parts:
-Anterior Pituitary (Adenohypophysis): Produces hormones under hypothalamic control.
-Posterior Pituitary (Neurohypophysis): Stores & releases hypothalamic hormones.
- 1cm diameter
7
Q
the hypothalamus
endocrine gland in brain
A
=control system that oversees internal body conditions, secretes hormones to regulate the pituitary.
-Located in lower diencephalon, above the pituitary.
Functions:
-Maintains homeostasis by monitoring blood conditions.
-Secretes releasing/inhibiting hormones to regulate the pituitary.
Communicates with the pituitary via two pathways:
1. Hypothalamo-hypophyseal tract (neural connection, for posterior pituitary).
2. Hypophyseal portal system (blood connection, for anterior pituitary).
8
Q
what is the infundibulum
A
=the hollow stalk which connects the hypothalamus and the posterior pituitary gland.
9
Q
the Hypothalamo-hypophysial tract
A
= connects the hypothalamus and the posterior pituitary
- communicate via neurons that extend through the infundibulum
-Hypothalamus makes neurohormones
- pass along neurons in the tract
- Stored in posterior pituitary until needed
- Released from post pituitary when hypothalamus detects need
10
Q
the Hypothalamhypophysial portal
A
= connects the anterior pituitary to the hypothalamus directly via portal blood vessels
- eventually the portal blood merges again with the general circulation
- Ant pit secretes tropic hormones - stimulate secretion of other hormones within other glands
11
Q
Hormone Regulation Example
A
GHRH (Growth Hormone-Releasing Hormone) → Stimulates GH production.
GHIH (Growth Hormone-Inhibiting Hormone) → Stops GH production.
- GHIH released through portal, through the blood reaching the anterior pituitary
12
Q
Endocrine Regulation (Axis Concept)
A
axis = when glands signal to each other in sequence
example: hypothalamus pituatary thyroid axis
- Hypothalamus → Produces TRH (Thyrotropin-releasing hormone) to stimulate pituitary
- Anterior Pituitary → Produces TSH (Thyroid-stimulating hormone)
- Thyroid Gland (target) → Produces T3 (Triiodothyronine) & T4 (Thyroxine).- the hormone
- Negative Feedback: High levels of T3/T4 inhibit TRH & TSH production. (feedback to hypothalamus)
13
Q
describe the thyroid gland
A
Location: Neck, lateral to trachea, connected by isthmus.
- large (~20g)
- made up of 2 lobes
-Highly vascularized (dark red appearance).
Controlled by:
TRH (from hypothalamus).
TSH (from anterior pituitary).
Hormones Produced:
-T3 (Triiodothyronine) & T4 (Thyroxine) → Increase metabolism.
-Calcitonin (from parafollicular/C cells) → Lowers blood calcium/ involved in calcium homeostasis
14
Q
Describe the thyroid gland histology
A
-Follicles: Spheres lined by simple cuboidal epithelial cells.
-Iodine-dependent (needed for T3 & T4 hormone production).
- iodine obtained from diet through seafood, dairy
- follicles store, produce and release T3 and T4 in response to TSH stimuli from pituitary
15
Q
describe the parathyroid glands
A
Four small glands of thyroid glands located on the posterior thyroid.
Hormone produced: Parathyroid Hormone (PTH) → Increases blood calcium.
Cell Types it’s made up of:
Chief cells → Small, dark-stained, produce PTH.
Oxyphil cells → Larger, lighter-stained function unknown.
16
Q
the adrenal glands
A
located = on top of kidneys
Structure:
- capsule (outermost layer)
- cortex (3 layers that produce steroid hormones)
- Zona Glomerulosa → Aldosterone (salt balance).
Zona Fasciculata → Cortisol (stress response).
Zona Reticularis → Androgens (sex hormones). - medulla ( produce Epinephrine (Adrenaline) + Norepinephrine (Noradrenaline).
17
Q
what is cushing’s syndrome
A
Cause: Excess cortisol produced from adrenal glands.
Symptoms:
Weight gain.
Thin skin.
Excessive sweating.
Causes:
Pituitary tumor (excess ACTH stimulates adrenal overactivity).
Long-term steroid use (e.g., for immune suppression).
18
Q
describe the pancreas
A
Dual-function gland (both endocrine & exocrine).
Location: Behind stomach, near duodenum.
- 15cm long, 85-100g
Endocrine function:
-Pancreatic Islets of Langerhans secrete hormones into circulation
- regulate nutrient concentration in circulation
exocrine function:
- acini produce pancreatic juice which are carried in duct to small intestine
19
Q
Pancreatic Islet Cells & Hormones
A
beta(B):
- hormone = insulin
- target tissue = liver, skeletal muscle, adipose tissue
- response = increased uptake and use of glucose and amino acids
alpha (a):
- hormone = glucagon
- target tissue = liver
- response = increased breakdown of glycogen; release of glucose into the circulatory system
delta:
- hormone = somatostatin
- target tissue = alpha and beta cells
- response = inhibition of insulin and glucagon secretion
- 1 million islets of langerhans in pancreas
- distributed along exocrine ducts
- each islet has each type of the above cell
20
Q
Central Regulation of Endocrine Glands
A
- Hypothalamus monitors homeostasis.
- Hypothalamus signals pituitary (via hormones).
- Pituitary releases hormones → Stimulates specific endocrine glands.
- Glands release hormones into the bloodstream.
- Hormones reach target organs → Physiological effects occur.
- Negative feedback: High hormone levels inhibit further hormone release.
21
Q
the basics of cell signalling
A
Cells communicate via:
1. Direct membrane-to-membrane contact
2.Release of “messengers” (chemicals, peptides, neurotransmitters, hormones)
Hormones are the messengers of the endocrine system, carrying signals from endocrine glands to various body cells.
22
Q
the three main structural classes of hormone
A
- Peptide/Protein Hormones:
-Hydrophilic
- lipid derived
- bind to cell surface receptors
- inactivated by gastric acid and peptidases - Steroid Hormones:
-Hydrophobic
-derived from cholesterol
-transported by carrier proteins
- typically lipid soluble - Amine Hormones:
-Derived from amino acids tyrosine and tryptophan
- bind to intracellular receptors
-(e.g., thyroid hormone, adrenaline)
23
Q
proccesses involved in cell signalling
A
- synthesis of signalling molecule in the signalling cell
- release of signalling molecule by the signalling cell
- transport of signalling molecule to the target cell
- detection of signalling molecule by a specific receptor protein on/in the target cell
- change in target cell function triggered by a receptor-signal complex
- inactivation/ removal of signalling molecule
24
Q
what are the different types of cell signalling
A
- Endocrine Signaling: Long-range (e.g., insulin)
- Paracrine Signaling: Short-range (affects nearby cells)
- Autocrine Signaling: Very short range (same cell)
- Membrane Protein Contact: No messenger, direct protein interaction between cells
25
insulin as an example of endocrine signalling
- release of insulin by B-cells in the pancreas, travels in the bloodstream and acts on liver, muscle and fat cells
- long range
- signalling molecule released by endocrine cell directly into bloodstream and carried in blood to distant target cells
26
somatostatin as an example of paracrine signalling
- somatostatin release by pancreatic delta cells act locally.
- signalling molecules released into extracellular fluid and affect target cells in close proximity to secreting cells.
27
neurotransmitters as an example of autocrine signalling
- most neurotransmitters and many growth factors bind to receptors on the cells that release them
- signalling molecules released into extracellular fluid and affect cells from which they were released
28
example of membrane protein contact
- siganlling by T cells in the immune system
- proteins expressed on the surface of the siganlling cell interact with receptor proteins expressed on the surface of the target cell
- direct contact
29
overview of signal transduction
Most signaling molecules do not enter cells. Instead, they bind to membrane-bound receptors, triggering intracellular signaling pathways.
Second messengers inside the cell are crucial for converting receptor activation into a functional change.
30
Receptors Involved in Signal Transduction: ligand gated ion channels
| also known as ionotropic receptors
-Found in electrically excitable cells that can transmit an electrical impulse (e.g., nerve, muscle cells).
-Ligand binding causes a conformational change in the receptor, opening an ion pore.
-Resulting ion flux leads to a change in membrane potential (depolarization or hyperpolarization).
Example: Acetylcholine receptor (nicotinic acetylcholine receptor) involves ion flux regulated by an alpha, beta, gamma, delta structure.
- takes milliseconds to happen
31
receptors involved in signal transduction: G protein-coupled receptors
| metabotrophic receptors
-Large family of receptors linked to G proteins (trimeric: composed of α, β, γ subunits).
- binding either GTP or GDP
-Ligand binding activates the G protein, which then activates/inhibits enzymes to generate intracellular second messengers.
-Important for amplifying signals and regulating a wide variety of cellular processes.
GPCR Pathways Overview:
Ligand binding → G protein activation → Secondary messenger cascade (e.g., cAMP, IP3) → Cellular response.
- takes seconds
- all G-protein-coupled receptors have 7 transmembrane spanning regiosn with (NH3+) on the extracellular side and (COO-) on cytoplasmic side of plasma membrane
32
what determines if a response is inhibitory or stimulatory
- is largely determined by which G-protein it interacts with
GPCRs coupled to Gi inhibit their targets (reducing enzyme activity)
GPCRs coupled to Gs stimulate their targets (increase enzyme activity).
33
receptors involved in signal transduction: kinase-linked receptors
Large group of receptors primarily responding to protein mediators (e.g., growth factors, cytokines).
Composed of:
-Extracellular ligand-binding domain
-Single transmembrane helix
-Intracellular domain (often enzymatic)
These receptors often activate intracellular signaling cascades (e.g., MAP kinase cascade, JAK-STAT pathway).
Feedback mechanisms help amplify signals.
- takes hours
receptor enzyme complex -> protein phosphorylation -> gene transcription -> protein synthesis -> cellular effects
34
receptors involved in signal transduction: Nuclear receptors
| NRs
-Regulate gene transcription.
-Ligand binding leads to receptor migration into the nucleus, where it can interact with DNA to regulate gene expression.
- can induce expression of enzymes that metabolize foreign substances
Two main classes off nuclear receptors:
-Class I: Ligand binds in the cytosol before moving to the nucleus. (ligands mainly endocrine in nature)
-Class II: Ligand binding typically occurs in the nucleus itself. (ligands are usually lipids)
Example: Cortisol, a steroid hormone, binds to cytosolic receptors before translocating to the nucleus to activate gene expression.(type 1)
35
the 5 steps of the type 1 nuclear receptors
1. ligand binding and detachment of HSP
2. dimerization of receptor hormone complex
3. translocation to nucleus
4. binding of NR dimer to DNA
5. gene expression and cellular response
- all occuring in the cytosol
36
the 5 steps of type 2 nuclear receptors
1. ligand binding to receptor causes dissociation of corepressor
2. recruitment of coactivator protein
3. recruitment of proteins for transcription
4. gene expression and cellular response
- receptor is inside the nucleus bound to corepressor
37
which type of receptor for which signal type?
1. agonist (glucagon, adrenaline, parathyroid hormone, somatostatin) -> g-protein activation -> generation of second messenger -> activation of cell signalling
2. agonist (insulin, cytokines, growth factors) -> phosphorylation of tyrosines on key signalling molecules -> activation of cell signalling
3. agonist (thyroxine, oestrogen, cortisol, testosterone) -> transport to the nuclues bypassing the membrane -> activation of transcription and translation
38
Signal Amplification
- a single ligand binding to a receptor can trigger a cascade of intracellular events, leading to a massive response from just a small initial signal.
- allows cells to respond strongly to low concentrations of signalling molecule
- rapidly spreads the signal across the cell
- enables fine tuned responses to environmental changes
- essential for processes like hormone signalling, immune responses and neurotransmisson
39
Quick Recap of the Concepts of the mechanisms of signal transduction
1. Ligand-Gated Ion Channels: Signal molecule opens a channel to let ions in/out, changing the electrical charge of the cell.
2. GPCRs: Signal molecule activates a G protein, which then activates second messengers inside the cell to amplify the signal.
3. Kinase-Linked Receptors: Signal molecule activates an enzyme (kinase) inside the receptor, triggering a chain reaction that leads to changes inside the cell.
4. Nuclear Receptors: Signal molecule enters the cell, binds to a receptor, and directly influences gene expression in the nucleus.
40
proteins and polypeptides
| Hormone Categories (Based on Chemical Structure)
example hormones:
- insulin, GH, TSH
- most common type
example sites of synthesis:
- anterior/posterior pituitary, pancreas, parathyroid
chemical nature:
- hydrophillic, cannot cross cell membranes
- so act on membrane bound receptors
synthesis:
- synthesized in advance- often as prohormones that require further processing to be active
storage:
- commonly stored in vesicles within the cell until the teigger to release
release:
- exocytosis
transport in blood:
- primarily dissolved in plasma
41
Steroids
| Hormone Categories (Based on Chemical Structure)
example hormone:
- cortisol, oestrogen
example site of synthesis:
- adrenal cortex, ovaries, testes, placenta
chemical nature:
- hydrophobic
- Lipid-soluble, freely cross membranes
synthesis:
- synthesized on demand in a series of reaction pathways from cholestrol
storage:
- not stored prior to secretion; released upon their synthesis
release:
- simple diffusion
transport in blood:
- primarily bound to plasma proteins
42
amino acid derivatives; thyroid hormones
| Hormone Categories (Based on Chemical Structure)
example hormone:
- thyroxine
example site of synthesis:
thyroid
chemical nature:
- hydrophobic
synthesis:
- synthesized from tyrosine (iodination)
storage:
- made in advance, stored as colloid in thyroid follicles
release:
- transport protein
transport in blood;
- bound to plasma proteins
(similar properties to proteins)
43
amino acid derivative - catecholamines
| Hormone Categories (Based on Chemical Structure)
example:
- adrenaline
site of synthesis:
adrenal medulla
chemical nature:
hydrophillic
synthesis;
synthesized from tyrosine (hydroxyl group and amine group only)
storage:
- in secretory vesicles
release;
exocytosis
transport in blood;
freely dissolved
(similar properties to proteins
44
Peptide Hormone Synthesis
1. Ribosomes synthesize pre-prohormone → Directed into rough ER
2. Signal peptide removed → Becomes prohormone
3. Prohormone packaged in Golgi apparatus → Stored in vesicles
4. Released via exocytosis when triggered
Example: Insulin (C-peptide removed before activation)
45
Steroid Hormone Synthesis
1. Cholesterol transported to mitochondria (rate-limiting step)
2. Enzyme action in smooth ER & mitochondria → Final steroid hormone
3. Not stored (made on demand) → Diffuses freely out of the cell
4. Transported in blood bound to plasma proteins (inactive until free)
Produced in:
Adrenal cortex → Cortisol, Aldosterone
Gonads → Testosterone, Estrogen
Placenta → Progesterone
46
mechanism of peptide hormone action
| (Fast-acting, Membrane Receptors)
-Bind to G-protein coupled receptors (GPCRs)
-Activate second messenger cascades (e.g., cAMP) → Signal amplification
-Leads to rapid cellular response
- modifying existing proteins
47
mechanism of steroid hormone action
| (Slow-acting, Intracellular Receptors)
-Cross membrane & bind intracellular receptors (cytoplasm or nuclues)
-Hormone-receptor complex moves to nucleus, binds promoter region → Gene transcription
-Leads to long-term changes in protein synthesis and cellular function
- promotes or suppresses gene transcription
- synthesises new proteins
48
mechanism of action of thyroid hormones and catecholamines
thyroid hormones:
- target tissue receptor is intracellular
- promotes or suppresses gene transcripton
- synthesises new proteins
catecholamines:
- target tissue receptor is on the cell surface
- activates second messenger system
- modifies exisiting proteins
49
negative feedback loops
| control of hormone secretion
1. Response driven
- based on the direct effect's of a hormones actions
- Hormone secretion adjusts based on a physiological variable
- hormone -> target organ -> physiological effect -> circulating component -> negative feedback -> endocrine gland
- Example: Blood glucose increases → Insulin released → Glucose uptake → Blood glucose drops → Insulin stops
2. Axis-driven
- regulation of multiple hormones within an endocrine axis, often through a series of glands in a sequential pathway.(involving hypothalamus and pituitary)
- Example: Hypothalamus → Releases CRH (releasing hormone) → Stimulates Pituitary → Releases ACTH → Stimulates Adrenal Cortex (target organ) → Releases Cortisol (hormone) → Cortisol negatively feeds back
50
concept of a general negative feedback loop
a system where the output of a process reduces or reverses the initial input, aiming to maintain stability or homeostasis
51
Positive Feedback
| (Rare, Leads to an Event)
= The feedback signal or output from the controlled system increases the action of the controlled system.
Example: Childbirth (Oxytocin)
Uterine contractions → Cervix stretch → Nerve signals to brain → Oxytocin release → More contractions → Baby delivered
52
Feed-Forward Control
| (Anticipatory Response)
= a direct effect of the stimulus on the control system before the action of the feedback signal occurs.
Example: Cortisol secretion in circadian rhythm
Light detected → Retina signals hypothalamus → Cortisol increases before waking → Prepares body for daily stress
53
Endocrine Control of Fluid & Sodium Balance:
key organs and hormones
1. Hypothalamus → Detects blood osmolality changes via osmoreceptors, regulates ADH release
2. Posterior Pituitary → Releases ADH in response to signals from hypothalamus → Kidney water reabsorption
3. Kidneys → Respond to:
ADH → Increases water reabsorption
Aldosterone → Increases sodium reabsorption & potassium excretion
4. Adrenal Glands → Releases/secretes Aldosterone in response to signals from RAAS system
heart- releases ANP
skin- sweat glands
liver- produces angiotensinogen
54
the regulation of fluid and electrolytes
- the body lacks dedicated receptors for specifically monitoring fluid or electrolyte balance
- response is due to changes in plasma volume or osmotic concentrations
- Fluid or electrolyte content in the body changes based on dietary intake and environmental losses (variable so we need tight control of it)
55
Antidiuretic Hormone (ADH)
| Water Retention
## Footnote
also called vasopressin
Released when: Blood osmolality increases (dehydration) -> enhances water reabsorption in the kidneys
action:
Binds to V2 receptors in kidney → Increases aquaporin-2 insertion in collecting ducts → More water reabsorbed
Also acts on V1 receptors in arterioles → Vasoconstriction (increases BP)
Effect:
Less urine output → More water retained → Blood osmolality normalizes
water deficit -> increased extracellular osmolarity -> increased ADH secretion from posterior pituitary -> increased plasma ADH -> increased H20 permeability in distal tubules, collectimg ducts -> increased H20 reabsorption -> less water excreted -> negative feedback
56
Aldosterone – Sodium Retention
Released when: Low blood sodium or low blood volume
- Secreted by the adrenal glands in response to signals from the Renin-Angiotensin-Aldosterone System (RAAS).
Action:
Stimulates ENaC channels in distal convoluted tubule → Sodium reabsorbed → Water follows → Blood volume increases
K+ excretion increases
Effect:
Maintains sodium balance, blood pressure & volume
57
aldosterone and water regulation in distal tubule
- water does not automatically follow sodium in DCT
- aldesterone promotes increased absorption of sodium in DCT -> increasing blood osmolarity -> stimulates production of ADH
- ADH enables water reabsorption in the collecting duct aswell as thirst.
- the combined effects result in an increase in extracellular fluid volume
- the net effect of increased sodium reabsorption, ADH action and thirst stimulation leads to an overall increase in blood pressure
58
Natriuretic Peptides (e.g., ANP)
- released by the heart in response to increased atrial stretch
- induces sodium secretion and water excretion by the kidneys
59
mechanism of action of ADH
1. ADH binds to the V2 receptor
2. catalyses the formation of cAMP
3. activates protein kinase A which initiates phosphorylation of intracellular structures
intracellular response:
- vesicles containing aquaporin 2 are translocated and inserted into apical membrane
outcome:
- Enables increased water permeability of the collecting duct.
-Water is absorbed by osmosis into the blood.
60
action of thirst to regulate water intake
Hypothalamus detects osmolality increase → Triggers thirst → Increased water intake
stimulating factors:
- increase in plasma osmolarity
- decrease in plasma volume
response:
- stimulation of hypothalamic thirst centre
- results in a conscious sensation of thirst
- ingestion and absorption of fluid decreases plasma osmolarity
61
the net effects of ADH
If someone has no ADH produced by hypothalamus -> very dilute urine as water cannot get from urine back into bloodstream
- ADH decreases blood osmolarity (reduction of concentration of solutes in the blood)
- increases blood volume (enhancing water retention in kidneys)
- decreased ADH -> more degradation of aquaporin
62
ADH secretion patterns and clinical consideration
-It is thought that in females, the kidneys may be more sensitive to the effects of ADH, potentially influencing urinary patterns.
-The absence of the diurnal rhythm with aging may contribute to the increased prevalence of nocturia (nighttime urination) in older adults.
* In adults, there is an increase in ADH secretion during the night.
* This nocturnal rise contributes to reduced urine production overnight.
* A delay or disruption in this diurnal pattern may be a contributing factor in children with nocturnal enuresis (bedwetting).
* Desmopressin, a synthetic form of ADH, can be utilized as a treatment to regulate nocturnal urine production.
63
stimulating the production of aldesterone
- decreased blood pressure or volume -> activates renin-angiotensin system
- renin converts angiotensinogen to angiotensin I
- angiotensin I to II by converting enzyme (ACE)
- angiotensin II stimulates production of aldesterone
- promotes reabsorption of sodium and water in distal convoluted tubule and collecting duct
64
aldesterone mechanism of action
intracellular receptor = MR which is found in cytoplasm of renal tubular cells
action:
- aldesterone binds to MR forming complex
- complex translocates to the nucleus and initiates transcription and protein synthesis for channels
target channels:
- epithelial sodium channels (ENaC) which facilitates sodium reabsorption
- potassium channels present for excretion
sodium transfer:
Na+/K+ ATPase - transfers sodium to blood
65
ADH and aldesterone as part of a complex integrated system
ADH:
- released in response to increased osmolarity
- increases aquaporins in renal tubular membrane, decreasing osmolarity
- concentrates urine
aldesterone:
- released in response to loss of blood volume
- increases sodium reabsorption and indirectly increases volume
atrial natriuretic peptide:
promotes the loss of water and sodium counteracting the above twos effect
angiotensin II
- stimulates thirst
- causes vasocontriction, regualting blood pressure
66
histology of the adrenal cortex
3 zones:
1. Zona glomerulosa
- cluster of small cells
- fewer lipids than other layers
- aldosterone, regulated by angiotensin II
2. Zona fasciculata
- large cells arranged in cords
- cortisol, regulated by ACTH
3. Zona reticularis.
- Smaller cells, haphazard arrangement
- adrenal adrogens regulated by ACTH and other factors
Each zone synthesizes different types of steroid hormones.
67
histology of thyroid gland
- composed of numerous spherical follicles
- follicles are lined with single layer of cuboidal epithelial cells (follicular cells)
- follilces are filled with colloid- composed of thyroglobulin, which stores the thyroid hormones
- vascular network surrounds each follicle
- Contains scattered C cells which produce calcitonin, involved in calcium metabolism.
- Recognisable due to colloid
- Epithelial can change in size depending on activity
68
Adrenal Cortex Steroid Hormones synthesis
| synthetic pathways
All pathways start with cholesterol → pregnenolone (rate-limiting step).
The subsequent steps differ depending on the hormone being synthesized (e.g., cortisol, aldosterone).
69
molecular mechanism of cortisol action
- cortisol is transported in plasma bound to corticosteroid-binding globulin (CBG). (its own binding protein)
-Target cell receptor in cytoplasm (glucocorticoid receptor)
* Initiates / represses gene expression (usually initiating)
70
actions of cortisol
| catabolic hormone
-affects most cells in the body and is essential for life
Metabolism: Stimulates gluconeogenesis(liver), lipolysis(adipose tissue), proteolysis(muscle).
Blood glucose: Essential for maintaining blood glucose during fasting; antagonistic to insulin.
Stress Response: Mobilizes energy reserves and prioritizes glucose supply for the brain.
Anti-inflammatory: Inhibits immune responses.
Electrolyte balance: Increases sodium reabsorption and potassium secretion.
Bone: Mobilizes calcium, leading to bone resorption.
71
the regulation of cortisol secretion
factors inputting to the CRH:
- Emotional stress
- physical stress
- circadian rhythm
- metabolic stress
- inflammation and infection
CRH -> ACTH -> cortisol
- Adrenal gland stimulated to produce cortisol, negative feedback to hypothalamus and anterior pituitary to reduce further secretion
- ACTH = hormone
72
therapeutic use of cortisol
- Corticosteroid drugs (e.g. prednisolone) usually have a mixture of glucocorticoid (like cortisol) and mineralocorticoid (like aldosterone) effects
- replacement ( Adrenal insufficiency in Addison’s Disease)
Anti-inflammatory & Immunosuppressant
e.g. Asthma, eczema, arthritis, inflammatory bowel disease, prevention of transplant rejection
-Long-term use of cortisol drugs can suppress natural cortisol production.
-Individuals on long-term corticosteroids should carry an emergency card for higher doses during acute illness.
73
Iodine
Iodine:
Essential for thyroid hormone synthesis (daily requirement: 150µg).
Found in fish, dairy, vegetables, and seaweed.
Iodine deficiency can cause endemic goiter.
Iodized salt is a common preventative measure.
74
the thyroid hormones
- amino acid derivatives synthesised from tyrosine
- T3 = triiodothyronine (tyrosine with 3 iodines added)
- T4 = tetraiodothyronine (thyroxine) (tyrosine with 4 iodines added)
-T3 and T4 are hydrophobic and thus bound to proteins, particularly TBG (thyroxine-binding globulin) for transport
-T4 is a prohormone, and only T3 is biologically active.
75
Thyroglobulin
-synthesized by follicular cells (ER and Golgi).
- is a large glycoprotein
- Each molecule contains about 70 Tyrosines
*Once formed, thyroglobulin is exocytosed into the thyroid follicle lumen
- Thyroglobulin is site of synthesis and storage of T3 & T4
76
Thyroid Hormone Synthesis
-Iodine is added to thyroglobulin in the thyroid follicle.
-Pendrin moves iodide into the follicle by active transport.
-T3 (triiodothyronine) and T4 (thyroxine) are synthesized and stored on thyroglobulin.
-T3 is the active form; T4 is a prohormone that gets converted to T3 by removing one iodine atom.
77
thyroid hormone regulation
-T3 and T4 feedback negatively to suppress TRH and TSH secretion.
-Thyroid hormones regulate growth, bone maturation, and basal metabolic rate.
-thyrotropin releasing hormone (TRH) from hypothalamus stimulates TSH secretion
- thyroid stimulating hormone (TSH) from pituitary increases secretion of T3 and T4
- TSH and TRH production are inhibited by T3and T4.
78
Thyroid Hormone Actions:
Growth and Development: Important for normal bone and brain development.
Metabolism: Regulates basal metabolic rate, influencing energy expenditure.
Thermogenesis: Helps in heat production and thermoregulation.
- increase oxygen consuption, increasing Na+/K+ ATPase activity
- provides substrates for metabolism
79
Congenital Hypothyroidism
| The importance of thyroid hormones:
-Occurs due to underdeveloped or absent thyroid gland in newborns.
-Neonatal screening (blood spot test) looks for elevated TSH (suggests thyroid dysfunction).
-Treatment: Levothyroxine (T4) replacement therapy, typically initiated by 3 weeks of age.
Effects when untreated:
- delayed puberty, infertility, delayed bone age, reduced muscle tone, cognitive impairment, constipation.
80
Cortisol Feedback Mechanism:
Cortisol secretion is regulated by ACTH from the anterior pituitary.
Negative feedback loop: High cortisol levels suppress further ACTH and CRH release.
Therapeutic use: Corticosteroid drugs like prednisolone mimic cortisol’s effects.
81
Thyroid Hormone Feedback Mechanism
T3 and T4 inhibit the release of TRH (thyrotropin-releasing hormone) from the hypothalamus and TSH from the pituitary gland.
This feedback regulates thyroid hormone levels within a narrow range to maintain homeostasis.
82
Cortisol Regulation:
ACTH stimulates cortisol production from the adrenal gland.
Cortisol provides negative feedback to reduce ACTH and CRH (corticotropin-releasing hormone) secretion.
83
the steps of thyroid action
T4 -> T3 -> T3 + nuclear receptor -> transcription of DNA -> Translation of mRNA -> synthesis of new proteins -> growth, nervous system, metabolism...
- T3 and t4 enter cell via an ATP dependent carrier
- T4 converted to T3
- T3 is transported to nuclei and binds to receptor
- thyroid hormone receptors bind DNA causing conformational change
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hyperthyroidism
| condition when the thyroid isn't working
Cause: Excess thyroid hormones (↑ metabolic rate).
Symptoms: Sweating, tremor, weight loss, heat sensitivity, tachycardia.
2 conditions:
1. diffuse toxic goitre
- autoimmune disease where antibodies to the TSH receptor stimulate thyroxine secretion
2. toxic nodular goitre
- caused by benign tumour or malignant adenoms
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hypothyroidism
| when thyroid is not working
Cause: Underactive thyroid (autoimmune).
Symptoms: Lethargy, cold sensitivity, bradycardia, thick skin, cretinism in children, slow speech, low metablic rate, mental impairment
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drugs used to treat hyperthyroidism
1. Radioactive iodine (¹³⁵I):
-Orally taken single dose lasting 2 months
targets thyroid by damaging cells, emitting B-radiation, affecting follicle cells
-leads to hypothyroidism; treated with replacement therapy
2. Thioureylene drugs
-(e.g., carbimazole and propylthiouracil)
-Inhibit thyroid hormone synthesis.
- inhibit thyroperoxidase enzyme reducing the iodination of thyroglobulin
- acts over 3-4 weeks
3. Iodine
- (high dose orally)
- Reduces hormone secretion and vascularity of the gland
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drugs used to treat hypothyroidism
- first line treatment is hormone replacement
1. Levothyroxine: action of synthetic thyroxine (T4), 1st line.
2. Liothyronine: action of synthetic T3, used in myxoedema coma.
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treatments of type 1 diabetes
Cause: Autoimmune destruction of β-cells → no insulin.
Treatment:
Insulin replacement
-by subcutaneous injection
-Types:
rapid acting (3-4 hours)
Short (6-8 hours)
intermediate (13-20 hours)
long-acting >24 hours
-(mimic physiological pattern).
-Monitor glucose; dose matched to food.
-Now uses recombinant human insulin.
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treatment and causes of type 2 diabetes
Cause: Insulin resistance + β-cell dysfunction (linked to obesity).
Onset: >40 yrs, gradual.
Treatment:
Lifestyle changes first (diet/exercise).
Oral antidiabetic drugs.
May need insulin later
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the 4 main types of antidiabetic drugs for type 2 diabetes
1. insulin sensitisers
- increase the sensitivity of insulin in muscle, liver and fat cells
2. Insulin secretagogues
- stimulate the release of insulin from pancreas
3. incretin-mimetics
- enhance or mimic action of incretin hormones that stimulate insulin release from the pancreas
4. glucose reabsorption inhibitors
- encourage renal exretion of glucose
- last 3 require functioning pancreatic B-cells
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metaformin in treating type 2 diabetes
1st line: Improves insulin resistance
↓ hepatic gluconeogenesis
↑ muscle glucose uptake
reduces absorption of carbohydrates from the gut
action;
-Activates AMP-kinase in hepatic cells
- increased nuclear receptor expression
- Reduced expression of genes involved in gluconeogenesis
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Thiazolidinediones in treating type 2 diabetes
Main compounds: rosiglitazone, pioglitazone
- improves insulin resistance by:
- reducing hepatic output
- increasing muscle glucose uptake
- reducing blood gucose and insulin
action:
PPAR-γ agonists alter gene expression:
↑ GLUT4, ↓ hepatic glucose output.
altered genes include:
- lioprotein lipase
- fatty acid transporter
- glut4
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Sulphonylureas & Meglitinides in treating type 2 diabetes
-Stimulate insulin release from vesicular stores in B-cells
- by blocking K⁺ channels → depolarization → ↑ Ca²⁺.
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incretin hormones in type 2 diabetes
- are metabolic hormones produced in GI tract
GLP-1 & GIP: ↑ insulin, ↓ glucagon, ↓ gastric emptying, ↑ satiety.
- stimulate release of insulin from β-cells following a meal but prior to increase in blood glucose
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gliptins in T2D treatment
main compounds: sitagliptin, vildagliptin, saxagliptin
- competitive inhibitors of the enzyme DDP-4 which is responsible for metabolism of GLP-1 and GIP
- Reduce blood glucose by inhibiting metabolism of incretin hormones leading to decrease in glucagon release, increase in insulin release
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when is insulin secretion more pronnounced
following oral vs intravenous administration of glucose; suggests GI involvement
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GLP-1 receptor agonists
Main compounds: exenatide, liraglutide, lixisenatide, by injection
* Increase insulin release from β-cells; reduce glucagon release from a-cells
- mimics action of GLP-1 in pancreas with longer lasting effects
* Slows gastric emptying; promote satiety- feeling more full
- semaglutide (ozempic) - longer acting and more effective than other drugs
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Gliflozins (SGLT2 inhibitors)
-Promote urinary glucose loss.
-Used in T1 and T2 diabetes.
- By blocking the sodium glucose co-transporter (SGLT2)
- causes excretion of blood glucose
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Addison's disease
| disorder of adrenal function
Cause: Adrenal insufficiency → ↓ cortisol, aldosterone.
- adrenal cortex does not make enough steroid hormones
Treatment: Life-long hormone replacement
- oral hydrocortsone to replace cortisol
- oral fludrocortisone to replace aldesterone
- oral dehydroepiandesterone as androgen replacement
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Cushing’s Syndrome
| Disorders of Adrenal Function
Cause: ↑ adrenal activity (↑ cortisol).
Untreated: Can be fatal.
- gland is working too much
- usually caused by tumours in piuitary or adrenal gland
treatment:
- surgery, radiotherapy to remove tumour, drugs to reduce cortisol production or effects
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Hormonal control of the reproductive system
- GnRH produced in hypothalamus regulates pituitary function
- FSH and LH are secreted by anterior pituitary
- acting on the endocrine targets testes and ovaries
- testes produce androgens
- ovary produces estrogen and progesterone with act on reproductive tracts and other tissues
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what does oestrogen cause
* Maturation of reproductive organs.
* Development of secondary sexual characteristics.
* Accelerated linear growth.
* Closure of the epiphyses (the end part) of long bones.
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drugs used for contraception
Combined Pill (COCP)
-Oestrogen + Progestogen
Inhibits: GnRH, FSH, LH → stops ovulation & implantation.
Progestogen-Only Pill (POP)
Thickens cervical mucus, inhibits ovulation.
Examples: norethisterone, levonorgestrel.
both prevent pregnancy by:
- inhibiting GnRH release from hypothalamus
- inhibiting FSH and LH release from pituitary gland
- reduces likelihood of implantation
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pathway of GLP-1, GIP and DPP-4 inhibitors
meal ingested -> secretion of GLP-1 and GIP in the GI tract by incretin actions -> in b cells in the pancreas their action causes increased insulin release and increased cellular glucose uptake
- in a cells they cause suppressed glucagon release -> supressed glucose production -> decreased hepatic output
DPP-4 inhibitor can inactivate them in the GI tract
