ENDOCRINOLOGY - lectures 9-10 Flashcards
what types of stimuli will cause an endocrine gland to release hormones?
- Humoral: in response to changing levels of ions or nutrients in the blood (as regulated by feedback mechanisms that maintain homeostasis)
- Hormonal: stimulation received from other hormones (leading to the rhythmic release of hormones ie hormone levels rising and falling in a predictable pattern, as regulated by feedback mechanism)
- Neural: stimulation by nerves (leading to hormone release in short bursts or spurts as required - as opposed to in a steady rhythm, as regulated by feedback mechanisms)
what does the hypothalamus do in terms of endocrine glands?
- controls anterior pituitary hormone release
- Releasing hormones
- Secreted like neurotransmitters from neuronal axons into capillaries and veins to anterior
pituitary (adenohypophysis)
how does the hypothalamus regulate secretion of pituitary hormones
- The hypothalamus contains neurons that secrete hormones that strictly control secretion of hormones from the anterior pituitary
↳ Releasing hormones
↳ Inhibiting hormones
↳ Hypothalamic releasing and inhibiting hormones are
carried directly to the anterior pituitary cells, modulating the release of hormone they produce
what hormones are produced by the anterior lobe?
- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Growth hormone (GH)
- Follicle stimulating hormone (FSH)
- Luteinising hormone (LH)
- Prolactin (PRL)
- Melanocyte Stimulating hormone (MSH)
what is the thyroid’s functions
- Thyroid hormone increases the overall metabolic rate, regulates growth and development, as well as the onset of sexual maturity
- Calcitonin lowers Ca ++
- Slowing the calcium releasing activity of osteoclasts in bone and decreases calcium reabsorption by the kidney
-Parathyroid hormone (PTH) raises Ca ++
- Parathyroid glands - maintain the body’s calcium and phosphate levels by secreting PTH
- Stimulates osteoclasts to release more Ca ++ from bone and decreases secretion of Ca
++ by kidney
Vitamin D - stimulated by parathyroid
- Uptake of Ca++ (and P) from the intestine
what is hypothyroidism?
- More common in medium dogs to large dog breeds usually middle ages dogs
Clinical signs: - Reduced metabolism
- Hair loss
- Cold intolerant
- Slow heart rate (bradycardia) - Lethargic
- Weight gain
Treatment:
- Thyroxine (T4)
- Some require T3
what is hyperthyroidism?
Results in increased metabolism
- Increased thyroid hormones secretion
- Most common endocrine disorder in cats - middle aged to old cats
- Clinical signs:
- Excessive appetite - Matted hair coat
- Nervousness
- Weight loss
- Elevated body temperature and heart rate - - Elevated T4
Treatment:
- Anti-thyroid medication
- Radioactive iodine therapy - Surgery and diet
What hormones are produced by the adrenal cortex and adrenal medulla>
- Adrenocorticotrophic hormone (ACTH) by anterior pituitary in response to stress/low cortisol and acts on the adrenal glands
- cortex secretes steroid hormones -> cortisol
What are the 3 adrenal cortex layers and what do they each do
- Outer zona glomerulosa: Primarily involved in production of mineralocorticoids (i.e. aldosterone)
- Middle zona fasciculata: Responsible for production of glucocorticoids (i.e. cortisol)
- Inner zona reticularis: Primarily involved in production of sex hormones (i.e. androgens, estrogens).
what is the function of cortisol
- Redirects circulating lymphocytes to lymphoid
and peripheral tissues where pathogens usually are - Enhances the activity of epinephrine
- counteracts insulin in pancreas, increases glucagon
- decreases glucose uptake in muscle
- decreases glycogen synthesis in liver
- reduces bone formatin
why is cortisol so important
- helps the body maintain homeostasis under stress
- In the liver it increases the availability of blood glucose to the brain by increasing
gluconeogenesis and decreasing glycogen synthesis - In the muscles, it decreases glucose uptake and consumption and increases protein degradation
- In adipose tissues, cortisol increases lipolysis (breakdown of fats)resulting in the reals of
glycerol and free fatty acids
What is Addison’s disease in dogs?
- Lack of cortisol (and aldosterone)
- Idiopathic/immune destruction of adrenal gland
- > 90% of the adrenal cortex is destroyed
- Young to middle age female dogs
Non specific clinical signs:
- Drink more water
- Urinate more often - Heart complications - Diarrhea
- Vomiting
how is Addison’s disease diagnosed
Treatment:
- increasing the dog’s fluid volume, correcting electrolyte imbalances, providing daily glucocorticoids (Prednisolone), and/or mineralocorticoids, such as Fludrocortisone, monitoring urine production etc.
What is Cushing’s disease? Diagnosis and treatment
- Overproduction of cortisol
- Usually caused by an ACTH-secreting pituitary tumour
- Long term use of corticosteroid drugs can cause signs of cushing’s disease
- Common in middle aged, small breeds (terriers, poodles and dashunds)
Clinical signs: - Excessive drinking and urination - Bald patches
- Pot belly
Diagnosis:
- Low dose dexamethasone (synthetic cortisol) suppression test (sensitive test)
- No negative feedback loop = cushings disease - cortisol would remain high
Treatment:
- Daily medication to reduce steroid production
What is the function of the growth hormone
- major participant in control of several complex physiologic processes, including growth and metabolism.
- GH-releasing hormone stimulates release of GH
- GH-inhibiting hormone suppresses the release of GH.
- The hypothalamus maintains homeostatic levels of GH.
- GH also causes increase in bone length and thickness by deposition of cartilage at the ends of bones.
- During adolescence, sex hormones cause replacement of cartilage by bone, halting further bone growth even though GH is still present.
what are the two types of effects of the growth hormone
- Direct effects: Results of growth hormone binding its receptor on target cells
- Indirect effects are mediated primarily by a insulin-like growth factor-1 (IGF-1), a hormone that is secreted from the liver and other tissues in response to growth hormone. A majority of the growth promoting effects of growth hormone is actually due to IGF-1 acting on its target cells.
what is Acromegaly in cats and dogs
- Overproduction of GH in adult animals
- Excessive bone growth, soft tissue and cartilage growth
- Increased body size, enlarged head, & organs that are larger than normal.
- long jaw, large paws, & increased space between the teeth
Dogs: excess progesterone exposure
- Anti-insulin effects - diabetes
- administration of progestational compounds for the suppression of - oestrus in intact female dogs.
Cats almost always a benign pituitary tumor
- older male cats
- No treatment
Diagnosis – IGF1 levels
what does anterioor pituitary do in terms of sex hormones
- produces Luteinising hormone (LH) which stimulates follicles
what is the effect of stimulating the gonads?
Gonads are the main source of sex hormones:
- In males, promotes testosterone production and sperm development
- In females, promotes estrogen, stimulates ovulation and promote egg development - Preparation of the body for possible pregnancy
What are the non reporoductive effects of sex hormones
- Assist in minimising the loss of calcium from bones and thus helping to keep bones strong
- Promote blood clotting
what occurs in the posterior pituitary gland?
- The posterior pituitary consists mostly of axons from hypothalamic neurons and support cells.
- Hormones from hypothalamus are forwarded and stored in axons in posterior pituitary.
- The hormones are released in response to neural impulses
- principal hormons are oxytocin and antidiuretic hormone (ADH)
what do oxytocin and ADH do?
- Oxytocin - initiates labour, milk ejection
- Antidiuretic hormone (ADH) - key role is to help maintain fluid homeostasis
- Stimulates distal convoluted tubule cells (DCT) of kidney nephron to reabsorb water
- Inadequate recreation causes diabetes insidious
- Copious amounts of diluted urine produced
- Intense thirst
What causes diabetes Inspidius (DI - in dogs and cats)
- ADH deficiency leads to watery urine, polydipsia, a condition known as diabetes insipidus (DI), a condition in which inadequate amounts of antidiuretic hormone are produced by the posterior lobe of the pituitary gland.
- This is associated with decreased ability of the kidney to concentrate the urine, resulting in excessive urination, thirst, and body fluid and blood sodium level imbalances.
- May be inherited, or it may result from tumors in or injuries to the pituitary or hypothalamus
what is the diagnosis and treatment for diabetes
Diagnosis:
- Excessive urination - 4-16 litres a day or more
- Excessive thirst
- Inability to quench thirst
- - Dry skin and mucous
- Constipation
- Muscle weakness
Dehydration
Treatment
- synthetic ADH
What gland secretes melatonin?
pineal gland
what does melatonin do?
- determines circadian rhythms
- Melatonin has important effects on reproductive function of many animals
- Melatonin synthesis and release of melatonin is stimulated by darkness and
inhibited by light, blood levels of melatonin are essentially undetectable during the daytime, rise sharply at night. - Inhibited by light (highest at night)
- Photoperiod - the length of day versus night
- the most important cue allowing animals to determine which season it is.
- Inhibits LH and FSH (via GnIH)
- Sheep - short day breeders
- reproduction activated by short days and inhibited by long days.
Horses: long day breeders - reproduction activated by long days
- Cattle and pigs are not seasonal
- even though melatonin changes occur, does not impact sperm production or female cyclicity
What are the two broad classes of hormones
- Steroid hormones
- peptide hormones
What are steroid hormones?
- Lipid derived
- Can pass through cell membrane
- Bind to intracellular receptors resulting in DNA
transcription
What are peptide hormones
- Not lipid derived
- Cannot pass through cell membrane, bind to receptors on surface of membrane
- Interact with plasma membrane receptors and are coupled to signal transduction systems
how do steroid hormones act
- exert their action by passing through the plasma membrane and binding to intracellular receptors.
- The steroid hormone-receptor complexes exert their action by binding to specific nucleotide sequences in the DNA of responsive genes.
- These DNA sequences are identified as hormone response elements, HREs, and are short specific sequences of DNA which are located in promoters of hormone-responsive genes.
- The interaction of steroid-receptor complexes with DNA leads to altered rates of transcription of the associated genes.
- Thus, the mechanism of action of steroid hormones is to modulate gene expression in target cells.
- By selectively affecting transcription from a battery of genes, the concentration of those respective proteins are altered, which clearly can change the phenotype of the cell.
What is cAMP/Adenylate cyclase pathway
- Pathway begins when hormone binds to receptor
1. Hormone binds to receptor, binding activates G protein, causing it to exchange its bound GDP for GTP
2. Activated G-proteins binds
adenylate cyclase (activating it)
3. Activated adenylate cyclase
cAMP/Adenylate cyclase pathway produces cAMP
4. cAMP activates protein kinase A - Protein kinase A activated by
cAMP - Phosphorylates other proteins
- Switches them on/off
- Cascade of cellular events
5. Protein kinase A phosphorylates
other proteins
how does epinephrine (adrenaline) use the cAMP/Adenylate cyclase pathway?
- Adrenaline is produced from adrenal medulla, travels in blood to target cell in liver, binds to target cells on surface
- Hormone binding activates receptor
- Activated receptor activates G-protein
- G protein exchanges its bound GDP for GTP (once GTP is bound, it is now an active G protein) - Activated G protein activates adenylate cyclase
- Activated adenylate cycle catalyses the synthesis of cAMP from ATP
- cAMP binds to regulatory subunits of protein kinase A, activating the catalytic subunits. Catalytic subunits phosphorylates one of its multiple targets - the CREB transcription factor
- Stimulates transcription of CRE regulated genes. In liver cells CRE containing genes encode enzymes involved in glucose production
- Eventually G-protein hyrdolyses its bound GTP and GDP. cAMP levels are also regulated.
- cAMP is continuously degraded by a specific phosphodiesterase
What is Cholera and what causes it
- Cholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae
- Produces cholera toxin which is a G protein inhibitor
- Toxin binds to G protein,
Inhibits conversion of GTP to GDP leaving the G protein permentanty switched on - Permanently switched on
causes increased secretion of water in the intestine. which can produce massive diarrhea - Severe dehydration can cause death
- One of the most rapid fatal illnesses known
- Various countries weaponised cholera toxin for ChemBio warfare
How can cancer be caused by a G protein disease?
- RAS Oncogene is a G protein
- Ras controls both proliferation and differentiation pathways
- Endogenous GTPase activity -> Turns itself off by converting GTP to GDP
- Mutations destroy GTPase activity
- Point mutations
- Constantly signalling
- A single amino acid mutation of Ras is found in more than 30% of all cancers
- As many as 90% of certain tumors have mutant Ras
what are tyrosine kinase receptors
- When no hormone is bound receptor exists as a monomer
- Binding of hormone causes receptors to dimerise
- Receptor dimerisation initiates intracellular signalling
- Receptor phosphorylates tyrosine residues onitself - active
- Eventually receptor is switched off by tyrosine phosphatases
What is the growth factor and what is its receptor
- Example of a hormone whose receptor is a tyrosine kinase.
- The receptor normally exists in a monomeric form but when growth factor binds to the extracellular domain, it causes the receptor to dimerise which in turn activates
why is the receptor of insulin significant?
- receptor is a tyrosine kinase.
- Insulin generates its intracellular effects by binding to a plasma membrane receptor, which is the same in all cells.
- The insulin receptor is an integral membrane glycoprotein with an a2ß2 tetrameric structure, which is stabilised by disulphide bonds.
- The alpha subunits of the insulin receptor are located outside the cell membrane and apparently serve as the insulin-binding site.
- When insulin binds to the alpha subunits, the ß subunits become active tyrosine kinases and phosphorylate their own tyrosine residues (auto- phosphorylation).
- The ß units then phosphorylate the tyrosine residues on other protein kinases, which then produce the cellular effects
