Endocrine System Flashcards
Name the endocrine glands.
Thyroid Parathyroid Pineal Pituitary Adrenal Pancreas Ovaries Testes
Name and describe the 4 main hormones that regulate metabolism.
- Insulin – produced from the pancreas and secreted in the fed state
- Glucagon – produced by the pancreas and signals the starved state
- Adrenaline – produced by the adrenal glands and is secreted in starvation and stress
- Glucocorticoids – produced by adrenal glands and are secreted in starvation and stress
What is hormone signalling?
Hormones are released by cells in these endocrine glands and enter the bloodstream, where they travel to and affect target cells.
Many cells that do not sit within endocrine glands also produce molecules which as hormones.
What are the 4 types of hormones?
- Amines – small molecules derived from amino acids, such as thyroid hormone, the catecholamines, adrenaline and noradrenaline.
- Peptides/polypeptides – larger molecules, products of genes, such as insulin, glucagon and growth hormone.
- Steroids – derived from cholesterol, such as vitamin D, glucocorticoids and the sex hormones.
- Fatty acid derivatives – prostaglandins, leukotrienes and thromboxanes.
Define signal transduction.
The process by which cells can respond to changes in their environment.
What are some general features of hormone signalling?
- Extracellular signalling molecules bind to specific protein receptors and initiate a cascade of signalling events inside the cell.
- An important factor in cell signalling is amplification. This is so that a small amount of hormone can bring about larger changes in the body, such as changes in metabolism, gene expression or changes in cell shape or movement.
- Cells must be able to ‘switch off’ the intracellular signalling events once the signal concentration falls.
How do hydrophilic and hydrophobic hormones bind to receptors to initiate signal transduction?
Hydrophilic/polar hormones cannot cross the plasma membrane s must bind to cell surface receptors that are embedded in the cell membrane. They have a specific binding region to which the hormone binds.
Hydrophobic molecules such as steroid hormones are not water soluble and tend to move around in the circulation, bound to a carrier protein. At their target tissues, they can diffuse across the cell membrane and interact with intracellular receptors.
What are short and long term cellular responses?
Short term – normally brought about by changes to existing cellular proteins that alter their function.
Long term – take minutes or hour to become apparent. Generally, changes in gene expression are involved here. These types of cell signalling responses change the amount of particular proteins inside the cell.
Describe the action of insulin on glucose homeostasis.
- Secreted in response to high blood glucose by the beta cells of the pancreas
- Signals the fed state
- Promotes glucose uptake into tissues and fuel storage
Describe the action of glucagon on glucose homeostasis.
- Secreted in response to low blood glucose by alpha cells of the pancreas
- Signals the fasting state
- Promotes fuel metabolism and glucose release by the liver
Describe the action of adrenaline on glucose homeostasis.
- Secreted in response to low blood glucose and fear via the adrenal medulla
- Stimulates fuel mobilisation, especially in muscle and adipose tissue
Describe the action of glucocorticoids on glucose homeostasis.
- Secreted largely in response to stress but also starvation
- Long term effects on the expression of enzymes involved in fat and carbohydrate metabolism
What range must glucose be regulated within?
3.5 to 6.5 mM
Describe the consequences of hypoglycaemia.
Many tissues are obligate or preferential glucose oxidisers. So anything leading to a precipitous fall in glucose is likely to be life-threatening. This is probably why animals have a number of hormones that work together (glucagon, adrenaline, glucocorticoids) to prevent hypoglycaemia.
Changes to brain function caused, including:
- Palpitations
- Nausea
- Shivering
- Drowsiness
- Unsteadiness
- Confusion
- Coma and death
Describe the consequences of hyperglycaemia.
More damaging in the long term.
- Osmotic diuresis/loss of fluid and electrolytes: dehydration, excessive thirst and diarrhoea.
- Glucose is a chemically active molecule that can covalently modify proteins causing glycosylation. So can manifest itself as microangiopathy/damage to the small blood vessels, such as in the nephron, macroangiopathy/damage to large blood vessels, leading to hypertension.
- Can also cause cataracts, from glucose metabolising to sorbitol that accumulates in the lens, and neuropathy.
How are hormone levels measured?
- Hormones are typically only present in normal animals in the blood at low concentrations.
- Hormone assays have to be very sensitive and specific and they commonly use antibodies made against the hormone of interest.
- ELISAs are frequently used and can also be used to detect pathogens or quantities of drugs.
Describe the brief histology of thyroid tissue.
Follicles containing colloid - a protein-rich viscous liquid. Follicles are surrounded by follicular/cuboidal epithelium.
Where are thyroid hormones derived?
From the amino acid, tyrosine.
Each follicle contains lots of thyroglobulin, a precursor polymer containing tyrosine. Cleaving the backbone of this molecule, and with the addition of iodines, produces the thyroid hormones.
Describe the process of thyroid hormone synthesis.
- Follicular cell synthesises enzymes and thyroglobulin for colloid.
- Iodide ions are co-transported into the cell with sodium ions and transported into the colloid.
- Enzymes add iodine to thyroglobulin to make T3 with 3 iodines and T4 with 4 iodines.
- Thyroglobulin is taken back into the cell.
- Intracellular enzymes separate T3 and T4 from the protein.
- Free T3 and T4 enter the circulation.
Describe the properties of T3.
- 10% proportion of total hormones released from the thyroid glands
- 5 times more active than T4
- Circulates loosely bound to a protein
- Half life = 1 day
Describe the properties of T4.
- 90% proportion of total hormones released from the thyroid gland
- 5 times less active than T3
- Circulates the blood tightly bound to a protein
- Half life = 6 days
What happens to T4 at tissues?
Most of the physiological effects of thyroid hormones are due to T3.
So, in target tissues, most T4 is deiodinated to T3.
T4 might be ‘pool or reserve’ for T3, so regulation of conversion of T4 to T3 is important.
Describe the action of thyroid hormones at target cells.
- Move around the body until they reach target cells.
- T3/4 enters the target cell.
- Most of T4 is converted to T3 by now.
- T3 enters the nucleus and binds to the thyroid hormone receptor, THR.
- Binding of THR to promotor elements activates gene transcription, which may have many effects of TH in different target cells.
Describe the hypothalamus-pituitary axis.
- Hypothalamus produces thyrotropin releasing hormone, TRH.
- TRH is transported along the hypophyseal portal circulation to the anterior pituitary.
- TRH binds to thyrotroph, cells that release thyroid-stimulating hormone.
- Thyrotrophs release TSH.
- TSH is transported in the bloodstream to the thyroid gland.
- Binds to the follicle cells in the thyroid gland.
- This increases T3 and T4 synthesis, by increasing the activity of the iodine pump, and so also increases the iodination of tyrosine. Increases the size, number and activity of the thyroid cells. This means there is an increase in re-uptake of the colloidal thyroglobulin.
Is TSH tropic or trophic?
Tropic hormones – hormones whose target is another endocrine cell.
Trophic hormone cause an increase in growth or size.
So, TSH is tropic and trophic.
What controls the release of TRH from the hypothalamus?
Sympathetic activation or the cold increase the amount of TRH released. Cortisol and growth hormone decrease TRH release.
In negative feedback, if T3 or T4 are high, TRH and TSH are supressed.
What is the cardiovascular effect of thyroid hormones?
- Thyroid hormone increases the manufacture and incorporation of beta-1 adrenergic receptors.
- This increases responsiveness and sets sensitivity of the heart to adrenaline and noradrenaline.
- Long term sensitivity of cardiac cells is regulated by plasma levels of thyroid hormone.
What is the effect of thyroid hormones on growth and development?
- Essential for normal growth in childhood. Action unclear but possible supporting action on growth hormone.
- Critical to development of the CNS. Lack of T3 and T4 in late foetal early neonatal period, there is irreversible failure of the CNS development in terms of number of neurones and myelination.
What is the effect of thyroid hormones on basal metabolic rate?
Basal metabolic rate – the rate at which the body uses energy to maintain vital functions whilst at rest.
- Oxidative metabolism increased in most cells.
- Stimulates catabolic and anabolic reactions, stimulates the synthesis of enzymes and structural proteins, more glucose made available to meet elevated metabolic demand, and increased lipid metabolism.
- Measured by increased heat production and increased oxygen consumption.
What are the possible causes of hyperthyroidism?
Tumours on follicular cells and Grave’s disease, which is an autoimmune disease.
One of the most common endocrine diseases in older cats, due to benign tumours or follicular disease. Rare in dogs, are dogs are more likely to be able to excrete any excess thyroid hormone.
What is the effect of hyperthyroidism?
Thyroid gland is increased in size (goiter). Cells undergo hyperplasia and hypertrophy (increase in size and number), which increases the rate of thyroid hormone secretion.
- Increased metabolic rate
- Effect on CVS: increased force of contraction and increased rate of contraction
- Effect on CNS: nervousness, irritability and sleeplessness
- Weight loss, fatigue, heat intolerance, sweating, moist skin
Describe what Grave’s disease is and its consequences.
An immunoglobulin/antibody is produced and released by lymphocytes in the body when it shouldn’t be. The immunoglobulin is thyroid stimulating antibody, a long acting thyroid stimulator.
- It can bind to the TSH receptor and cause T3 and T4 release.
- Increased basal metabolic rate, lots of enzyme activity leading to weight loss.
- This feeds backs and reduces the release of TRH and TSH, there is still gland enlargement/goiter and all the other symptoms.
What are some possible causes of hypothyroidism?
Iodine deficiency so T3 and T4 cannot be synthesised, or autoimmune destruction of thyroid cells in Hashimoto’s thyroiditis.
Well recognised in dogs, especially Doberman, Beagles and Golden Retrievers, and only sporadically in other species.
What are the effects of hypothyroidism?
- Decreased basal metabolic rate
- Increased body weight and decreased appetite
- Effect on CVS: decreased cardiac output, decreased force of contraction, decreased rate of contraction
- Effect on CNS: fatigue and mental sluggishness
- Myxoedema, cold intolerance and goiter
No T3 and T4 formation > no negative feedback on TSH and TRH > constantly stimulating thyroglobulin production > gland enlargement.
How can growth be measured?
- Quantitatively – body weight, height, length, amount of muscle mass
- Qualitatively – body proportions and functions. Muscle mass vs intramuscular fat mass
What is growth hormone, how does it travel in the blood and how does it take effect?
Peptide hormone that promotes hypertrophy, hyperplasia and differentiation of some cell types. Causes growth in almost all tissues of the body that can grow.
Binds to growth hormone receptors on target tissues. Released from anterior lobe of the pituitary gland (after stimulation from a hormone from the hypothalamus that travels to the anterior via the hypophyseal portal system in hypothalamus-pituitary-axis).
How does growth hormone travel and why?
Circulates weakly bound to growth hormone binding protein for rapid release into tissues.
Peptide hormones are hydrophobic so do not need to travel with a binding protein, unlike steroid hormones, but can travel with them to maintain their half-life so the body does not break them down as quickly.
What cells release growth hormone?
Somatotrophs release growth hormone into the body to have its effects around the body on different cell types and causing cell growth. Includes liver, bone and muscle growth.
When is growth hormone released?
Growth hormone released in pulsatile release and is released in more concentrated bursts when the animal is going to sleep (diurnal). Under control of neurons in the hypothalamus.
How is the release of growth hormone regulated?
- Hypothalamic peptide, growth hormone releasing hormone, is released in response to hypoglycaemia, sleep, stress, exercise and ghrelin (released in response to hunger). Act on somatotrophs and cause growth hormones release.
- Hypothalamic peptide, somatostatin, which acts on somatotrophs and prevents growth hormones release. Released in response to insulin like growth factor 1, obesity and hyperglycaemia.
- Growth hormones also has a negative feedback system on itself, decreasing its release when its concentration gets too high and vice versa. Is also able to bind to the hypothalamus and cause an increase in somatostatins to decrease growth hormone concentration.
What are the acute effects of growth hormone on metabolism and their collective function?
- Protein metabolism – increased amino acid uptake and utilisation, increased protein synthesis and decreased catabolism
- Lipid metabolism – decreased lipogenesis, so less lipids are stored and more is available for use in the bloodstream.
- Carbohydrate metabolism – decreased glucose uptake and oxidation, increased gluconeogenesis and glycogenolysis. Increased blood glucose so more is available in the blood for use. (Has the opposite effect to insulin so can be called diabetogenic and anti-insulin.)
These effects results in protecting proteins and prevents is breakdown.
