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)
8 primary endocrine glands
Secondary endocrine glands
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.
