endocrine system - Feb 8th & 15th Flashcards
Who was Claude Bernard?
- “father of modern physiology”
- stated that our internal environment remains remarkably constant despite changes in the external milieu
Who was Walter Canon?
coined the term “homeostasis” to describe the relative stability of the internal environment
What does homeostatic control rely on?
- sensor: constant monitoring
- integrating centre: coordinates
- response system: changes
Most systems operate in a ______ feedback manner
negative
Homeostasis is maintained largely in part by the ______ system
endocrine
What is the consequence of a hyper-function endocrine dysfunction?
Too much hormone
What is the consequence of a hypo-function endocrine dysfunction?
Too little hormone
What is the consequence of a resistance endocrine dysfunction?
hormone has too little effect
What is an endocrine gland?
- a tissue that secretes a substance into the blood stream
- substance then travels by the blood to influence a target cell
The Classic Minkowski experiment discovered _______
insulin
How did the Classic Minkowski experiment make its discovery?
- surgical removal of the pancreas in a dog resulted in dog developing diabetes
- implantation of pieces of pancreas under the skin of the dog resulted in prevention of symptoms of diabetes
What did Banting and Best discover?
- insulin
- identified antidiabetic substance in pancreatic extracts
- injection of these extracts prevents symptoms of diabetes (prevents elevated blood glucose)
Describe the four properties of insulin:
- peptide hormone produced by beta cells of pancreas
- promotes absorption of glucose from blood to skeletal muscle and fat tissue
- stored as hexamer, zinc ion and histadine residues in its inactive form
- in its active form it is a monomer
What are the four types of hormones?
- protein and polypeptide hormones (<100 amino acids)
- steroid hormones (cholesterol derivatives)
- glycoprotein hormones
- amine hormones (catecholamines or thyroid)
What is autocrine signaling
A signaling molecule targets sites on the same cell that it is secreted from
What is paracrine signaling?
A Secretory cell secretes signaling molecules that affects another target cell in close proximity
What is endocrine signaling?
signaling molecule secreted into blood by endocrine gland
signaling molecule travels via blood to target molecule
Which type(s) of hormone(s) is/are synthesized in advance?
- peptide
- amine (cat & thyroid)
which type(s) of hormone(s) is/are synthesized on demand?
steroid
Peptide and amine hormones are stored in _______
secretory vesicles
Which type(s) of hormone(s) is/are released from cell via exocytosis?
- peptide
- amine (cat)
Which type(s) of hormone(s) is/are released from cell via diffusion?
- steroid
- amine (thyroid)
Which type(s) of hormone(s) is/are transported in the blood by being dissolved in the plasma?
- peptide
- amine (cat)
Which type(s) of hormone(s) is/are transported in the blood by being bound to carrier proteins?
- steroid
- amine (thyroid)
Which type(s) of hormone(s) has/have a short half-life?
- peptide
- amine (cat)
Which type(s) of hormone(s) has/have a long half-life?
- steroid
- amine (thyroid)
insulin is an example of a(n) _______ type of hormone
peptide
Estrogen / androgen are examples of _______ type of hormone
steroid
Epinephrine / norepinephrine are examples of ________ type of hormone
amine (cat)
Thyroxine (T4) is an example of a(n) _______ type of hormone
amine (thyroid)
hormones bind to ______ in target cells
receptors
Receptors have very high ______ for a particular hormone
specificity
What happens when “hormone overspill” occurs?
non-specific protein-receptor binding
Receptors for most hormones are found in the _______ of target cells
plasma membrane
Receptors for ____ and _____ hormones are inside the target cells
- steroid
- thyroid
How do transmembrane receptors work?
- hormone binds to extracellular domain of receptor and activates one or more cytoplasmic signaling pathways
- many of these pathways involve phosphorylation and enzyme activation
- some pathways lead to DNA/mRNA/protein pathway response; other have local effect in target cell
What are the steps of the Adenylate Cyclase pathway?
- hormone binds G protein coupled receptor, G-proteins dissociate
- alpha subunit of G-protein activates adenylate cyclase (AC)
- AC catalyzes product of cAMP
- cAMP removes regulatory unit from PKA
- active PKA activates other molecules (hormonal response)
What are the steps of the epinephrine - adenylate cyclase pathway
- epinephrine binds to beta-adrenergic receptor on liver cell
- G-proteins activated - subunit carrying GDP dissociates - GDP -> GTP
- Subunit activated adenylyl cyclase which catalyzes ATP -> cAMP
- cAMP activates PKA, which activates phosphorylase
- Phosphorylase converts glycogen to glucose-6-phosphate
- glucose-6-phosphate -> glucose (released from liver)
What did Robert Lefkowitz and Brian Kobilka do?
- 2012 Nobel prize in Chem
- how cells in our body sense their environments
- focus on G protein coupled receptors
- understanding how these proteins work crucial to unravelling complex network of signaling between cells
What are the steps of the phospholipase C-Ca2+ pathway?
- Hormone binds GPCR, G-proteins dissociate
- Phospholipase C (PLC) is activated
- Active PLC causes breakdown of membrane phospholipid to IP3
- IP3 binds to endoplasmic reticulum
- Ca2+ released from ER into cytoplasm
- Ca2+ activates other molecules (hormonal response)
Alpha-adrenergic receptors activate ______
phospholipase C
Beta-adrenergic receptors activate ______
adenylate cyclase
Describe the mechanism by which steroid hormones carry out their functions
- they are lipophilic so they move across the plasma membrane bound to a carrier protein
- steroid hormone binds cell cytoplasm receptor
- translocates to the nucleus, binds to DNA and acts as a transcription factor
- stimulates gene transcription
- protein products
- response
What is the general mechanism of action of the hypothalamic-anterior pituitary-peripheral target axes?
Hypothalamic neuroendocrine cells (hormone 1 - blood vessel) -> Anterior Pituitary cells (hormone 2 - general circulation) -> Target tissue (endocrine or non-endocrine) (hormone 3 - general circulation) -> Tissue response
The pituitary gland is physically connected to the hypothalamus through a(n) ___________
infundibulum (stalk)
The ____ pituitary is the endocrine gland
anterior / adenohypophysis
The ____ pituitary is an extension of neural tissue
Posterior / neurhypophysis
What are the 7 hypothalamic hormones / factors?
- Dopamine (PIH)
- Prolactin releasing hormone (PRH)
- Thyrotropin-releasing hormone (TRH)
- Corticotropin-releasing hromone (CRH)
- Somatostatin (GHIH)
- Growth hormone releasing hormone (GHRH)
- Gonadotropin-releasing hormone (GnRH)
What is the function of dopamine (PIH)?
Inhibits prolactin secretion
what is the function of prolactin releasing hormone (PRH)?
stimulates release of prolactin
What is the function thyrotropin-releasing hormone (TRH)?
Regulates secretion of thyroid stimulating hormone (TSH)
What is the function of corticotropin-releasing hormone (CRH)?
regulates secretion of adrenocorticotropic hormone (ACTH)
What is the function of somatostatin (GHIH)?
inhibits secretion of growth hormone (GH)
What is the function of growth hormone releasing hormone (GHRH)?
stimulates secretion of growth hormone
What is the function of Gonadotropin-releasing hormone (GnRH)?
regulates secretion of gonadotropin-releasing hormones, lutenizing hormone (LH) and follicle stimulating hormone (FSH)
CRH is produced by ________ within the ________
parvocellular neuroendocrine cells ; hypothalamus
blood vessels carry the CRH peptides to the ____ where they stimulate ____ to secrete ______
anterior pituitary ; corticotropes ; adrenocorticotropic hormone (ACTH)
ACTH is in the ____ family
Proopiomelanocortin (POMC)
What are convertases?
- enzymes that cleave POMC
- Different convertases give rise to different products
What are the two tissues that make up the adrenal glands?
- adrenal cortex
- adrenal medulla
What is the function of the adrenal cortex?
Secretion of steroids (corticosteroids):
* Glucocorticoids (eg:cortisol)
* Mineralcorticoids (eg: aldosterone)
* Sex steroids (eg: testosterone)
What is the function of the adrenal medulla?
- secretes catecholamines (eg: epinephrine)
- (modified sympathetic ganglia)
Glucocortinoids are controlled by ______
ACTH
Mineralcorticoids are controlled by ________
Reninangiotensin system
Sex steroids are controlled by _____
ACTH
What are the three layers of the adrenal glands from innermost to outermost?
- Zona reticularis
- Zona fasciculata
- Zona glomerulosa
mineralocorticoids are found in the ____ layer of the adrenal glands
Zona Glomerulosa
Glucocorticoids are found in the ____ layer of the adrenal glands
zona fasciculata
Androgens are found in the ____ layer of the adrenal glands
Zona reticularis
Epinephrine is found in the ____ layer of the adrenal glands
medulla
Why is cortisol essential for life?
- protects against hypoglycemia (low blood sugar)
- promotes gluconeogenesis (increases blood sugar)
- plays a role in immune system (suppression of immune system, regulation of inflammatory response)
- causes breakdown of skeletal muscle for gluconeogenesis
- causes bone catabolism
- affects brain function (mood, memory, learning)
What is Cushing’s Syndrome **
- Primary hypercortisolism
- high blood corticosteroids (prolonged exposure to high cortisol levels)
- caused by glucocorticoid drugs or diseases that result in excess cortisol, ACTH or CRH
- changes in carb and protein metabolism, hyperglycemia, hypertension, muscular weakness
- puffy appearance, CNS disorders
What is Cushing’s Disease ?
- Secondary hypercortisolism
- high blood corticosteroids (prolonged exposure to high cortisol levels)
- pituitary-dependent (ie: tumour in pituitary gland produces large amounts of ACTH resulting in adrenals production of excess cortisol)
- ACTH levels are LOWER in Cushing’s SYNDROME
What is Addison’s Disease?
- Primary hypercortisolism
- low blood cortisol
- adrenal insufficiency
- cause by genetics, autoimmune dysfunction etc.
- can be acquired if high-dose steroids are taken for longer than one week (because of CRH and ACTH suppressions which suppresses adrenal glands
Describe the rhythm of adrenal cortisol secretion
Continuous, pulsatile, circadian release
What is pituitary pars intermedia dysfunction? (PPID)?
- in horses
- impaired pituitary (hyperplasia and hypertrophy of pars intermedia
- increases secretion of cortisol by adrenal glands
- high blood glucose and suppression of immune system
the ____ is the largest purely endocrine gland
thyroid
The thryoid gland is ____ lobes connected by _____
2 ; isthmus
thyroid ____ take up ____ from the blood
follicles ; iodide
in the ____ of the thyroid, ____ enzyme helps attach ____ to ____ in thyroglobulin
colloid ; thyroid peroxidase enzyme (TPO) ; iodide ; tyrosine residue
Thyroglobulin is made by _____
follicular cells
iodide is brought into follicular cells by _____
sodium-iodide transporter
After iodide is brought into the follicular cells it is brought into colloid by _____
pendrin transporter
____ removes an electron from iodide in the colloid to produce iodine
thyroid peroxidase enzyme (TPO)
What are the two possible outcomes of iodine binding tyrosine residues in thyroglobulin?
- one iodine on a tyrosine ring produces monoiodotyrosine (MIT)
- two iodines on a tyrosine ring produces diiodotyrosine (DIT)
Enzymes in the colloid modify the structures of MIT and DIT, joining them together to produce ____ or ______
- Triiodothyronine T3 (MIT + DIT)
- Tetraiodothyronine T4 (DIT + DIT)
Describe the steps of thyroid hormone synthesis after the formation of T3 and T4
- T3 and T4 still attached to thyroglobuline backbone
- thyroglobulin taken back up by follicular cells and cut, separating T3 and T4 upon stimulation by TSH
- T3 and T4 secreted out to bloodstream bound to carrier protein
Most thyroid hormones in blood circulation are bound to plasma carrier protein called _______
Thyroxin-binding globuline (TBG)
True or false: Thyroid hormones that are still bound to their carrier protein are active
False: hormones have to lose the carrier protein to be active
Is T4 or T3 more biologically active?
T3
What are the physiological actions of thyroid hormones
- elevate basal metabolic rate
- needed for normal gonadal development and function
- needed for normal embryonic/fetal development (CNS developments)
Is production of thyroid hormone typically higher in younger or older people
Younger
What are the consequences of Hypothyroidism?
- abnormally low BMR
- weight gain
- lethargy
- intolerance to cold
What are the consequences of hyperthyroidism?
- Increased BMR
- weight loss
- muscular weakness
- nervousness
- protruding eyes
What is Cretinism?
- congenital thyroid hormone deficiency (arising from maternal hypothyroidism or iodine deficiency)
- reduced physical growth and developmental delays
- Treatment with T4 soon after birth can restore mental development by age 5
What are goiters?
- abnormal thyroid growth due to hypothyroidism
- low iodide intake results in low thyroid hormone production
- low plasma thyroid hormones result in high TRH
- high TRH results in high plasma TSH
- High plasma TSH stimulates excess growth of thyroid
What is Graves Disease?
- due to hyperthyroidism
- autoimmune antibodies activate thyroid gland leading to high T3 and T4
- high thyroid hormone concentration leads to low TRH and low plasma TSH
- causes exophthalmia (protruding eyes)
Synthetic thyroid hormone medications contain only ____, this can be an issue because:
- T4
- T4 must be converted to T3 for it to work; conversion is done by de-iodinase and in some people this enzyme is deficient or not working; some providers might add Cytomel (T3) in addition to Synthroid (T4)
- Synthetic T3 and T4 still lacks T2 and T1 and calcitonin
