Hormomes 🩸 Flashcards
Explain the principle of hormonal release and feedback from the major endocrine organs. Include examples to help explain these concepts.
3 ways it’s triggered / controlled
Two types of feedback
Examples
Hormones: biologically active substances secreted by endocrine glands, go into the bloodstream to reach target organs to produce their effects.
Humoral trigger: changes in extra cellular fluid levels or ion levels eg decrease in calcium ion levels by the parathyroid glands cause a release of parathyroid hormone into the blood to increase calcium levels by stimulating release from stores.
Neaural transmitter release: neaural stimulation eg the sympathetic system releasing noradrenaline to stimulate hormone release from adrenal glands.
Hormonal : hormones released by other endocrine glands. Hypothalamus releasing tropic hormones from the adrenal gland, which regulate release of hormones from other glands eg thyroid gland, adrenal cortex, gonad)
Types of feedback
Negative feedback: endocrine gland senses too mic( of hormone, decreases production eg cortisol from adrenal. It feeds back on the anterior pituitary and the hypothalamus to stop releasing ACTH and CRH respectively. Helps keep blood conc of cortisol within narrow ranges.
Positive feedback: The release of the hormone increases the production of the hormone? Eg oxytocin causes muscle contractions and the action causes more hormone to be released, prolactin, oestrogen
Outline the basic mechanisms (receptors and signalling) by which different hormones exert their effects on target cells.
Amino acid hormones: receptor =
Lipid soluble hormones - steroids -
Peptide hormones- bind to tyrosine kinase receptors and that initiates the glucose translocation into the cell. Eg insulin. Receptor- GLUT4 (insulin sensitive glucose transporter)
G-protein coupled receptors activate G proteins which then initiate intracellular signalling cascades. Eg adrenaline binding beta receptors activating adenylate cyclase then ATP to cAMP. Secondary messenger amplifies the signals and activate protein kinase which leads to rapid changes in cellular activities.
Cytoplasmic? Nuclear?
Type 1 nuclear receptor = steroid receptor (intracellular receptors in cytoplasm)
Type 2 nuclear receptor = ligand activated transcription factors (directly alter gene transcription, in nucleus)
3 main chemical groups of hormones and summarise their key structural and physicochemical characteristics (e.g. molecular weight, lipophilicity, ionisation).
Amino acids: molecular weights below 500 Deltas. Low molecular weights. Derived from singular amino acids like tyrosine eg thyroid (c3/c4)or tryptophan. Can be hydrophilic or lipophilic. Can be ionised. They can cross the membrane. Positive charge or mixed.Eg melatonin, adrenaline
Peptide hormones: Bind to G protein receptors. High molecular weight. 500-5000+. Cannot pass through cell membrane (very big) . Positive/ negative/ neutral. eg insulin, glucagon, oxytocin
Lipid / steroid hormones: Below 500 molecular weight. Highly lipophilic, can pass through cell membrane. No charge.Eg cortisol, testosterone
relate endocrine gland/organ to its hormone, its chemical class and any potential application for the drugs. Consider what the aim of any related the treatment is – eg what does the drug have to do to normalise the pathophysiology of the disease state.
Structure
Large proteins- limited oral bioavailability -prone to enzymatic degradation - too large to pass through membrane- parental - injections
Small molecules - eg thyroid hormone — more stable - easily pass through membrane
Solubility
Lipophilic - absorbed in GI - can be oral as pass through easily
Stabilisation
Hormones prone to oxidation and hydrolysis and formulation protects. Prone to enzymatic degradation. To make more stable give as injection if gastric enzymes. Enteric coating.Sublingual.
Short half life eg insulin - to prolong action inject into fat layer (fat controls release)
How would you formulate a hydrophilic drug to cross the skin?
Add lipophilic coating eg liposomes
Transdermal patch sometimes
Add ethanol
Name the two types of feedback mechanisms in the endocrine system (1 mark). Explain how these mechanisms work using a particular hormone as an example (2 marks for each example).
Positive and negative feedback (1 mark)
Negative feedback: Cortisol levels are controlled by a negative feedback mechanism that increases or decrease release of CRH and ACTH to maintain homeostasis (2 marks, full explanation)
Positive feedback: Oxytocin release is stimulated by childbirth or breastfeeding which both causes additional release of the hormone which only stope when birth or breastfeeding is complete. (2 marks, complete explanation)
Indicative answer:
Negative and positive feedback mechanisms have to be named to get 1 mark.
As long as negative feedback is linked to a hormone (0.5marks), the system by which increases and decreases in the named hormone (1 mark) is controlled plus this is to maintain homeostasis (0.5marks) full marks can be achieved in multiple ways.
Oxytocin is really the only example that can be used as an example of positive feedback (0.5 marks). The physiological process that cause / inhibit release need to be given (childbirth and breastfeeding (1 mark) and cessation of these stops hormone release (0.5marks)
How do hormones act?
Altering rates of enzyme mediated reactions
Induces secretory activity
Stimulate mitosis
Control the movement of molecules across the plasma membrane
• May change membrane permeability or potential or both by opening or closing ion channels
Regulating the rate of gene expression
• Proteins, enzymes, regulatory molecules
Peptide / protein hormones
Cellular action mechanism
Lipophobic - must bind to receptors on membrane’s extracellular facing surface
Most work via G Protein coupled receptor signalling
• CAMP - adrenaline, ACTH, FSH, LH, glucagon, PTH, TSH, calcitonin
• IP3 - vasopressin (ADH), TSH, and angiotensin
Some via receptor-enzyme complexes
• Tyrosine kinase receptors - insulin
Steroid hormones
Lipophilic
No storage
• Production is on an “as needed” basis
• Can have the precursors in cytoplasm ready to go
Require protein transports in blood
Prolongs duration of hormone
It must disengage from carrier in order to enter cell
Steroid Hormones
Cellular mechanism of action
How they’re regulated
• Diffuses into cytosol and or into nucleus
• Acts as a transcription factors in nucleus to alter gene activity by
• Repressing or activating rates of transcription
• Lag period due to the processes that have to occur
Regulation
• Negative feedback loop - increased transcription factors cause a decrease in production
• Phosphorylation - may stop transcription
• Ligand binding to transcription factors or cofactors that regulate the transcription factors.
Target Cell Activation depends on 3 factors
- Blood levels of the hormone
- Relative number of receptors on or in the target cell
- Affinity of binding between receptor and hormone
Endocrine system
System of ductless glands that release hormones that control homeostasis and coordinate body functions.
Describe the metabolic effects of glucocorticoids (4 marks)
Glucocortocoids tell catecholamines to exert the lipolytic effect (1 mark) and also tell glucagon to exert calorigenic effects (1 mark). These steroid hormones also causes increased gluconeogenesis (1mark) and cause increased storage of glycogen in liver and in muscle (1mark). Glycogen is a polysaccharide whereas glucose is a monosaccharide.
Where is the glucocorticoid receptor found?
Cytoplasm
Hormone regulated cancers: Leukaemia: glucocorticoids
Prednisolone
Dexamethasone
Glucocorticoid receptor activation in white blood cells induce apoptosis
Synthetic antagonists
Stronger effects than natural ligands
Causes activation of proapoptotic (Bim)
Reduces activity of Mcl-1 (antiapoptotic)
Breast cancer
Some types can have oestrogen receptors, some are non-target cells with no oestrogen receptors
Oestrogen are sex steroid hormones. Secreted by ovaries (also placenta, adipose tissue, adrenal glands). I’m post menopausal, released not from ovaries but the rest.
Overweight causes more oestrogen (adipose tissue) = higher risk
Oestrogen receptor MOA: ER (ER alpha and beta) receptor, ligand binds (oestrogen) causes dimerisation, conformational change caused, can now bind to oestrogen response elements and activators and repressors (coregulators)
Drug: mimicked binding of estrogen. Cell proliferation controlled by oestrogen so a drug like tamoxifen can bind instead and avoid the transcriptional activity bc the conformational changes are different in the dimers so even if this receptor binds to the DNA, no transcriptional regulation HAS TO BE ESTROGEN RECEPTOR (ER) POSITIVE FOR THE EFFECTS OF TAMOXIFEN OR EVEN OESTROGEN TO BE THERE TISSUE HAS TO EXPRESS RECEPTOR. Selective estrogen receptor modulators (the drugs SERMS eg tamoxifen & raloxifene) won’t work for ER negative tumours
SERMs are ER ligands that in some tissue i.e. bone, liver and cardiovascular system) act like estrogens, block estrogen function in others (brain and breast tissue) and mixed agonist/antagonist in the uterus. This agonist activity can increase risk of endometrial cancer in the uterus (as given systemically). (Uterine cancer). Upon ligand binding, can stimulate cell proliferation & increase risk of cancer.
Breast cancer treatment options:
tamoxifen / raloxifen (SERMS)
1 tablet/day for 5yrs
Less will develop cancer while taking tablets with tamoxifen
Tamoxifen has longer benefits when stopped (11vs 2)
Raloxifen does NOT increase endometrial cancer risk unlike tamoxifen
Tamoxifen slightly increased risk of blood clots
Aromatise inhibitors
Post menopausal women (high plasma estrogen levels)
Stops production of estrogen on the other tissues eg fat tissue
Aromatise is the enzyme that coverts androgens to estrogens
This activity in peripheral tissues and local malignant and normal breast tissue supplies breast cancer cells with the estrogen that stimulates cancer growth
Aromatise inhibitors blocks production of this estrogen
Aromatase is a microsomal cytochrome P450 in which the ham protein binds the androgenic substrate and catalvzes a series of reactions hatlead to the formation of the onenolic A-ring.
Drug : Faslodex (fulvestrant)
No known agonist activity > used in post menopausal women after first line failed / advances disease . Alternative to tamoxifen
Post-menopausal, source of estrogen. High circulating estrogens associated with breast cancer in post-menopausal women
FASLODEX binds, blocks and degrades the ostrogen receptor, completely inhibiting estrogen receptor signalling (known as a SERD- selective estrogen receptor down regulator)
No oestrogen binding to tissue = tissue stops producing extra oestrogen receptors (good)
Postage cancer
Targeting Androgen receptors
Deplete androgen By eliminating production of testosterone(would have to remove testes)
Can inhibit enzyme involved in testosterone conversion to DHT in prostrate tissue
Inhibit binding of DHT to receptors
Inhibit production of adrenal androgens eg abiraterone
Goal: Stopping activation of androgen receptors to treat prostate cancer
PSA: prostate specific antigen (first line screening) to see any changes in prostate function. More than 4 units is at risk and needs to be followed up.
Q: Which gland has both endocrine and exocrine functions?
The pancreas (endocrine: insulin/glucagon; exocrine: digestive enzymes).
Q: What are the primary endocrine glands?
Hypothalamus???, pituitary, pineal, thyroid, parathyroid, thymus, adrenal, pancreas, ovaries/testes.
Q: Which endocrine gland controls circadian rhythm?
Pineal gland (secretes melatonin).
Q: What is the role of the adrenal glands?
Produce cortisol, adrenaline, aldosterone, and androgens; involved in stress response and homeostasis.
Q: How does the hypothalamus interact with the pituitary?
Releases hormones that stimulate the anterior pituitary to secrete other hormones.
Q: What are the three main classes of hormones?
Amines: Derived from tyrosine/tryptophan (e.g., adrenaline, melatonin).
Peptides/Proteins: Chains of amino acids (e.g., insulin, glucagon). Eg oxytocin
Steroids: Lipid-based, derived from cholesterol (e.g., cortisol, testosterone).
Q: What is the difference between peptide and protein hormones?
Peptides: Shorter chains of amino acids (e.g., oxytocin).
Proteins: Larger molecules with multiple chains (e.g., insulin).
Q: What are steroid hormones?
Lipid-soluble hormones derived from cholesterol; act on nuclear receptors to regulate gene expression.
Q: How do peptide/protein hormones act on cells?
Bind to extracellular receptors; activate second messengers like cAMP or IP3.
Use G-protein coupled receptors for signaling.
Eg insulin binding to kinase receptors
Q: How do steroid hormones act on cells?
Lipophilic; cross cell membranes to bind cytoplasmic or nuclear receptors.
Regulate gene transcription and protein synthesis.
Q: How does hormone level affect response?
Depends on hormone concentration, receptor number, and receptor affinity.
Q: What are the three types of hormone triggers?
Humoral: Blood levels of substances (e.g., low calcium triggers PTH release).
Neural: Nerve stimulation (e.g., sympathetic nerves trigger adrenaline release).
Hormonal: Hormones stimulating other glands (e.g., hypothalamus triggers anterior pituitary).
Q: What is the feedback mechanism for hormone control?
Negative Feedback: Maintains homeostasis by inhibiting overproduction (e.g., cortisol).
Positive Feedback: Enhances response (e.g., oxytocin during childbirth).
Q: How does the hypothalamic-pituitary-adrenal (HPA) axis work?
Hypothalamus releases CRH → Stimulates anterior pituitary to release ACTH → Stimulates adrenal cortex to release cortisol.
Cortisol provides negative feedback to inhibit CRH and ACTH release.
Q: What causes endocrine disorders?
Too much or too little hormone secretion.
Receptor issues (non-responsive or hyper-responsive).
Structural/functional gland changes (e.g., injury, genetic disorders).
Immune response or synthetic hormone imbalances.
Q: What are the roles of glucocorticoids and mineralocorticoids?
Glucocorticoids (e.g., cortisol): Regulate metabolism, reduce inflammation, suppress immunity.
Mineralocorticoids (e.g., aldosterone): Control electrolyte and water balance, regulate blood pressure.
Q: What is the function of oxytocin?
Stimulates uterine contractions during childbirth.
Promotes milk ejection during breastfeeding.
Associated with bonding (love hormone).
Q: What is the role of anti-diuretic hormone (ADH)?
Regulates water reabsorption in the kidneys to maintain fluid balance.
Q: What are examples of secondary endocrine organs and their hormones?
Heart: Atrial natriuretic peptide (regulates blood pressure).
Kidneys: Erythropoietin (stimulates RBC production), renin (regulates blood pressure).
Skin: Produces inactive vitamin D3 precursor.
GI Tract: Releases over 30 hormones (e.g., gastrin, incretins).
Q: How to remember anterior pituitary hormones?
Use the acronym FLAT PEG:
FSH, LH, ACTH, TSH, Prolactin, Endorphins, Growth Hormone.
Q: What factors influence hormone effects?
Hormone concentration in the blood.
Number of receptors on the target cell.
Hormone-receptor binding affinity.
Negative feedback regulation
Summary at bottom
Negative feedback is a regulatory mechanism where the increase in the level of a hormone suppresses its own production by inhibiting the glands or pathways responsible for its release.
This helps maintain homeostasis and prevents excessive hormone levels.
How it occurs:
Hypothalamic-Pituitary Axis (HPA):
The hypothalamus releases a releasing hormone (e.g., corticotropin-releasing hormone, CRH) that stimulates the anterior pituitary.
The anterior pituitary secretes a stimulating hormone (e.g., adrenocorticotropic hormone, ACTH) which acts on a target endocrine gland (e.g., adrenal cortex).
The target gland produces the final hormone (e.g., cortisol), which exerts its physiological effects.
Inhibition:
When cortisol levels rise to sufficient levels in the bloodstream:
Inhibits the hypothalamus: Reduces secretion of CRH.
Inhibits the anterior pituitary: Reduces secretion of ACTH.
This limits further cortisol release, maintaining balance.
Examples:
Thyroid Hormones (T3 and T4):
High levels of T3/T4 inhibit the hypothalamus (reducing thyrotropin-releasing hormone, TRH) and the anterior pituitary (reducing thyroid-stimulating hormone, TSH).
Cortisol (Stress Hormone):
High cortisol inhibits CRH release from the hypothalamus and ACTH release from the anterior pituitary.
Importance:
Prevents overproduction of hormones, avoiding toxicity or harmful effects.
Maintains stable levels of hormones required for physiological functions.
—————————-
Hypothalamic-Pituitary Axis (HPA):
Step 1: The hypothalamus releases a releasing hormone (e.g., CRH).
Step 2: The anterior pituitary secretes a stimulating hormone (e.g., ACTH).
Step 3: The target endocrine gland (e.g., adrenal cortex) produces the final hormone (e.g., cortisol).
Inhibition:
When hormone levels rise sufficiently:
Inhibits the hypothalamus → Reduces secretion of the releasing hormone (e.g., CRH).
Inhibits the anterior pituitary → Reduces secretion of the stimulating hormone (e.g., ACTH).
Outcome: Limits further hormone release to maintain balance.
Examples of Negative Feedback
Thyroid Hormones (T3/T4):
High T3/T4 levels inhibit:
Hypothalamus → Reduces thyrotropin-releasing hormone (TRH).
Anterior pituitary → Reduces thyroid-stimulating hormone (TSH).
Cortisol (Stress Hormone):
High cortisol levels inhibit:
Hypothalamus → Reduces corticotropin-releasing hormone (CRH).
Anterior pituitary → Reduces adrenocorticotropic hormone (ACTH).
Importance of Negative Feedback
Prevents overproduction of hormones, avoiding toxicity or harmful effects.
Maintains stable hormone levels required for physiological functions and homeostasis.
Q: What are the main characteristics of Type I steroid receptors?
Located in the cytoplasm, bound to heat shock proteins (HSPs).
Activated by steroid hormones like cortisol, aldosterone, or sex hormones.
Upon hormone binding, receptors dissociate from HSPs, dimerize, and translocate to the nucleus.
Bind to hormone response elements (HREs) in DNA to regulate gene transcription.
Q: What are the main characteristics of Type II steroid receptors?
Located in the nucleus, often bound to DNA.
Activated by steroid hormones like thyroid hormone, vitamin D, and retinoic acid.
Hormone binding causes conformational changes, allowing coactivator recruitment and gene transcription regulation.
Q: What are the consequences of steroid hormone activation of nuclear receptors?
Altered gene expression.
Modulation of protein synthesis for long-term cellular responses.
Effects on metabolism, growth, immune function, and development.
Q: What are the genomic actions of steroid hormones?
Steroid hormones bind to nuclear receptors (Type I or II).
Receptor-hormone complexes bind to specific HREs in DNA.
Regulate transcription of target genes, leading to protein synthesis.
These effects are slower and longer-lasting.
Q: What are the non-genomic actions of steroid hormones?
Steroid hormones bind to GPCRs (G-protein coupled receptors) on the cell membrane.
Activate secondary messenger pathways (e.g., cAMP, calcium signaling).
Rapid cellular responses such as ion channel modulation or enzyme activation.
Q: How does insulin bind to and activate tyrosine kinase receptors
Binding: Insulin binds to the extracellular domain of its tyrosine kinase receptor.
Dimerization: The receptor dimerizes and undergoes autophosphorylation of tyrosine residues.
Activation: Phosphorylated receptor recruits and activates intracellular signaling proteins (e.g., IRS).
Signaling: Activates pathways like PI3K-Akt and MAPK for glucose uptake, metabolism, and growth.
Q: How do amino acid-based hormones activate GPCRs?
Binding: Hormone (e.g., adrenaline, glucagon) binds to a GPCR on the cell membrane.
G-protein activation: GPCR activates an associated G-protein by exchanging GDP for GTP.
Effector activation: G-protein activates effector proteins like adenylyl cyclase or phospholipase C.
Second messengers: Secondary messengers (e.g., cAMP, IP3, DAG) are generated, leading to signal amplification.
Cellular response: Changes in cellular functions like enzyme activation or ion channel modulation.
Q: What are the key differences between genomic and non-genomic actions of steroid hormones?
Genomic:
Involves nuclear receptors.
Regulates gene expression.
Slow onset, long-lasting effects.
Non-genomic:
Involves GPCRs or other membrane-associated receptors.
Activates secondary messenger systems.
Rapid onset, short-term effects.
Q: What is the importance of tyrosine kinase receptor activation?
Mediates hormone actions like insulin for glucose metabolism.
Promotes growth, proliferation, and differentiation via pathways like PI3K-Akt and MAPK.
Q: How does GPCR signaling enhance hormone responses?
Amplifies signals through secondary messengers (e.g., cAMP).
Allows rapid and reversible responses.
Increases efficiency by coupling to diverse downstream pathways.
