Endocrinology Flashcards
What does the endocrine system regulate?
Metabolic activity - slow-acting and prolonged
What is endocrinology?
The study of the biosynthesis, storage, chemistry and physiological function of hormones and the cells that secrete them
What is a hormone?
A chemical substance, irrespective of whether it was produced by a special gland or not, that is exported or acts domestically to regulate certain cells/organs
What does the endocrine system consist of?
Several glands/tissues that secrete hormones into the blood circulation or extracellular space
What functions do hormones regulate?
Metabolism, growth/development, tissue function, mood and sexual reproduction
What are the four mechanisms of hormone release?
1) Endocrine: Classical hormones (released into the blood)
2) Paracrine: Communication between local cells
3) Autocrine: Acts on the same cell from which it was released
4) Neuroendocrine: Released by neurosecretory cells
What are the chemical classes of hormones?
1) Monoamines
2) Peptides/proteins
3) Lipids and phospholipids (steroids)
What do peptide/protein hormones consist of?
3 or more amino acid residues
Hormones secreted by the pituitary gland are what chemical class?
Peptide/protein hormones
Are peptide/protein hormones water or lipid soluble?
Water soluble, i.e. diffuse freely in the bloodstream
Describe an example of a protein/peptide hormone
Thyroid stimulating hormone (TSH)
- Released from the anterior pituitary
- Stimulates the synthesis and release of thyroid hormones (T3 & T4)
What are steroid hormones typically synthesised from?
Cholesterol
How many major groups of steroid hormones exist?
Five
Are steroid hormones generally stored?
No, they are rapidly synthesised on demand
Are steroid hormones water or lipid soluble?
Lipid soluble, i.e. diffuse freely across the cell membrane but require a carrier protein to travel in the bloodstream
Describe one example of a steroid hormone
Estrogens
- Secreted from the ovaries
- Promotes female reproductive system development
What are monoamines derived from?
Tyrosine
What are the two major groups of monoamine hormones?
Thyroid and catecholamines
Describe thyroid hormones
- Synthesised/stored in the thyroid gland
- Incorporated into thyroglobulin
- Released into the bloodstream following cleavage of thyroglobulin
- Combine with plasma transport proteins in the blood
Describe catecholamine hormones
- Synthesised in the nervous system and adrenal medulla
- Stored in vesicles and released through exocytosis
Describe an example of an amine hormone
Epinephrine
- Released from adrenal medulla
- Sympathetic stimulation
How are peptides and catecholamines transported?
Water soluble
- Cross the lipid membrane with carrier protein
- Diffuse freely in the bloodstream
How are steroids and thyroid hormones transported?
Lipid soluble
- May require a carrier protein to cross the lipid membrane
- Bind to carrier protein to travel in the bloodstream
- Biologically inactive until dissociated from the carrier protein
Where are hormone receptors located?
- Cell surface (peptide and catecholamines)
- Cell cytoplasm (steroids)
- Nucleus (thyroid hormones)
What are the two messenger (enzyme) systems activated by cell surface receptors?
1) Indirect (second messenger pathways): G-protein coupled receptors (cAMP)
2) Direct (primary kinase enzyme): Tyrosine kinase
What are protein kinases?
Specialised enzymes that chemically add a phosphate group to specific amino acid residues in a protein
What are the characteristics of G-protein coupled receptors?
- 7 transmembrane loops
- 3 coupled subunits
- Activation by hormone binding causes exchange of GDP for GTP, which breaks of a subunit through conformational change
- a subunit interacts with other cytoplasmic proteins altering the activity of ion channels/enzymes
Can hormones bind to an excitatory or inhibitory G-protein, or either?
Either
Describe the G-protein - cAMP pathway using epinephrine as an example
1) Epinephrine binds to its specific receptor
2) Causes replacement of the GDP bound to Gs with GTP, activating Gs
3) a subunit moves to adenylyl cyclase and activates it
4) Adenylyl cyclase catalyses the formation of cAMP
5) cAMP activates PKA
6) Phosphorylation of cellular proteins by PKA causes cellular response to epinephrine
7) cAMP is degraded
What are the 3 domains of receptor kinases?
Extracellular ligand-binding domain, transmembrane domain and intracellular enzyme (tyrosine-specific protein kinase)
How are tyrosine residues phosphorylated?
Ligand binds, causing the kinase to become active and phosphorylate tyrosine residues in target proteins, changing their activity
What is an example of a tyrosine kinase?
Insulin
What is insulin?
A hormone synthesised/released from the beta cells of the pancreas in response to high blood glucose levels
What effects does insulin cause?
- Uptake of glucose by liver, muscle and adipose cells
- Stimulation of glycogen synthesis
- Modulation of genes involved in cell growth and division
- Inhibition of glucagon synthesis/release
What is up-taken glucose used for?
- Energy
- Energy storage as glycogen
- Energy storage as fats
What happens when insulin binds to its receptor?
- Activation of kinase activity through auto-phosphorylation
- Activated kinase phosphorylates insulin receptor substrate-1 (IRS-1)
Describe the MAPK pathway for insulin
1) IRS-1 activates a specific protein complex
2) Induces phosphorylation cascade
3) Output: alterations in the expressions of genes
What happens when IRS-1 activates PI3K?
- PI3K converts the membrane lipid PIP2 to PIP3
- PIP3 activates protein kinase B (PKB)
Describe the two PKB pathways (insulin pathways 2 & 3)
Pathway 2:
- PKB induces phosphorylation cascade
- Inhibits the activity of glycogen synthase kinase 3
- Output: increased glycogen synthesis
Pathway 3:
- PKB stimulates movement of glucose transports (GLUT4) to the plasma membrane
- Output: Increased glucose uptake
Where can lipid soluble hormones (e.g. thyroid hormones) bind with receptors?
In the cytoplasm or nucleus
What structure connects the pituitary gland to the hypothalamus?
Hypophysial stalk
What are the two divisions of the pituitary gland, what type of tissue do they consist of and how are they regulated?
Anterior: Glandular tissue, regulated by hormones
Posterior: Neuronal tissues, regulated by nerve signals
Describe an example of an anterior pituitary hormone
Thyroid stimulating hormone (TSH)
- Cell: thyrotropes
- Stimulates thyroid hormone release from the thyroid (affecting general metabolism)
Describe the blood vessels connecting the hypothalamus/pituitary gland
Small vessels penetrate the hypothalamus (median eminence) and become the hypothalamic-hypophysial portal blood vessels
Specialised nerve ending from the hypothalamus secrete hormones into where?
The vessels within the median eminence
Describe an example of a major hypothalamic releasing/inhibiting hormone
Thyrotropin releasing hormone (TRH): Stimulates TSH secretion
Describe an example of a posterior pituitary hormone
Antidiuretic hormone (ADH)
- Formed in supraoptic nuclei of the hypothalamus
- Controls water excretion (kidneys - water channels and urea)
- Controls concentration of water, glucose ad salts in the blood
What are the two nuclei of the hypothalamus where hormones are produced?
Supraoptic and paraventricular
What is the posterior pituitary composed of?
Glial-like cells that do not secrete hormones, but support the neural end-feet
What receptors regulate the release of ADH, where are the located and what do they monitor?
- Osmoreceptors
- Located within or near the hypothalamus
- Monitor electrolyte levels circulating in the blood
What stimulates ADH release?
Increased blood electrolyte levels and decreased blood volume
What are the major thyroid hormones and what is their function?
T3 & T4 - Increase metabolic rates
What is the difference between T3 & T4?
1) Rate and intensity of secretion - T3 is four times more potent, but is present in the blood at lower quantities and for shorter periods of time
2) T4 is more stable for transport, but is mostly converted to T3 within the target tissues
Describe the structure of the thyroid gland
- Closed follicles filled with colloid (secretory substance)
- Cuboidal secretory cells
- Large glycoproteins (thyroglobulin) within the colloid which binds the hormones
What is required for the formation of thyroid hormones?
Iodine
Describe thyroid hormone synthesis
1) Iodine is transported into cells from blood
2) Iodine is transported into the follicle
3) Thyroglobulin is secreted into the follicle
4) Oxidation of iodine ions
5) Oxidised iodine binds with tyrosine molecule on thyroglobulin
6) Formation of T3 & T4 within the thyroglobulin
7) T3 & T4 stored within follicles attached to thyroglobulin
Describe thyroid hormone release
1) Formation of TSH droplets around colloid fluid
2) Protease enzymes digest the droplet thyroglobulin molecules, releasing T3 & T4
3) T3 & T4 diffuse through the cell membrane into surrounding capillaries and are transported by plasma proteins to all tissues
What do thyroid hormones increase?
- Development
- Number/activity of mitochondria
- Energy production
- Cardiovascular activity
- Respiration
- GI motility
How is thyroid hormone secretion regulated?
- Hypothalamus releases TRH
- AP gland releases TSH
- Thyroid gland releases T3 & T4
- Release of hormones stimulates AP gland and hypothalamus through negative feedback and indirect modulation
What is hyperthyroidism?
Excessive metabolism due to toxic goitre, adenoma or graves disease
What is hypothyroidism?
Reduced metabolism due to thyroiditis, colloid goitre or surgical removal of the thyroid gland
