(IEMR2)Hormones, Hormone Receptors and Mechanisms of Hormone Action Flashcards
Chemical transport take place through what general operations?(3-6 points)
Diffusion, Osmosis, faciliate transport, active transport, exocytosis, endocytosis and hormone transport in circulation
Most hormones are what type of macromolecule?
peptides or proteins
What are the three general type of hormone structures?(3 points)
protein and peptide hormones, steroid hormones, and tyrosine derivatives
What are examples of group of hormones in the group of tyrosine derivatives?(2 points)
**thyroid hormones **and catecholamines
What are examples or hormones that are synthesized form modified tryptophan?(1-2 points)
Serotonin and melatonin
Peptide hormones are synthesized in what general location?
they’re synthesized in the cell
How are peptide hormones synthesized and released generally speaking?(7 points)
Peptides hormones are transcribed from mRNA, **translated **into a polypeptide. This process creates a preprohormone. The preprohormone is modified to turn into a prohormone. the prohormone is modified and turned into a hormone. The hormone is stored in granules for release later due to the fact that synthesis takes a long time. The exocytosis of the hormone is calcium depedent.
What is longer, the synthesis of a peptide hormone or hte synthesis of a steroid hormone?
the synthesis of a peptide hormone
What tends to be generally larger, peptide hormones or steroid hormones?
steroid hormones tend to be bigger than peptide hormones
What has a longer half-life, peptide hormones or steroid hormones?
peptide hormones have a relatively shorter half-life than steroid hormones
What group of hormones in the body have the longest half-life?
thyroid hormones
What are examples of hormones that are produced by one gene, i.e., one gene producing one hormone?(1-2 points)
insulin and growth hormone
insulin is produced by one gene, two genes are multiple genes?
one gene
What gene is known to produce many hormones?
POMC
What are examples of hormones produced by the POMC gene?(2-3 points)
MSH, ACTH and α-endorphin
What are examples of hormones that are produced by two genes?(2-3 points)
FSH, LH and TSH
LH is produced by one gene, two genes are multiple genes?
two genes
TSH is produced by one gene, two genes are multiple genes?
two genes
How do peptide hormones exit the cell after processing is complete?
Peptide hormones exit the cell via calcium dependent exocytosis
What are the two general sources of cholesterol?(2 points)
Circulating LDL or synthesized from acetate
What basic intracellular step is necessary for the synthesis of steroids from cholesterol?
mobilzation of cholesterol into the mitochondria
How is cholesterol mobilized into the mitochondria for steroid hormone synthesis?
The StAR enzyme completes this step when it combines with cholesterol
Where is the location of StAR?
inner-mitochondrial membrane
What is the action of the enzyme StAR?(2 points)
Side chain cleavage to form pregnenolone
What exits the mitochondria after the action of StAR takes place?
pregnolone
What enzymes assist with the movement of pregnolone outside of the mitochondria?
SER(enzymes associated with smooth membranes in the cytoplasm)
What is SER?
enzymes associated with smooth membranes in the cytoplasm
Does pregnenolone re-enter the mitochondria or is it used immediately for the synthesis of steroid hormones?
It may require re-entry into the mitochondria
Why does stroage of steroid hormones take place?
they don’t
Is modification always necessary after secretion of steroid hormones?
yes, modification may be required
What are the three main classes of steroid hormones?(3 points)
mineralcorticoids, glucocorticoids and androgenstendione
What is the precursor and end substarte for the three main classes of steroids?(3-6 points)
**pregnenolone **goes through a series of steps to become aldosterone. 17-OH pregnenolone goes through a series of reactions to become cortisol. DHEA goes through a series of reactions to become androgenstendione.
What are two grouops of hormones that are modified tyrosine molecules?(2 points)
catecholamines and thyroid hormones
Where are catecholamines stored?
secretory vesicles
Where are thyroid hormones stored?
colloid
What special about the storage of thyroid hormones?
they stored in colloids and they’re formed as part of the thyroglobulin molecule
What specific group of hormones are water soluble?(2 points)
most peptides and amines
What large category of hormones are associated with proteins in plasma?
lipid soluble or hydrophobic hormones
Why do diabetics take insulin orally?
insulin doesn’t work orally because they’re going to be deactivated through the digestive process
What specific group of hormones have the longest half-life?
thyroid hormones
What is the relative half-life of peptides?
short
What is the relative half-life of catecholamines?
very short
What is the relatively half-life of steroids?
long
What is the initial event in hormone action?
binding of hormone to the receptor
The binding of the hormone to the receptor involves what properties of the interactions between the receptor and the hormone?(2 points)
The receptor affinity for the hormone it’s binding and the receptor specificity for the hormone it is binding
What general type of molecules are the hormone receptors?
proteins
The binding site for the hormone on the reeptor is referred to as what?
the effector site or the hormone binding site(s)
Stress induces the release of what specific hormone?
cortisol
What provides specificity for hormone-cell interaction?
receptors
Where is the general location of hormone receptors?(3 points)
cell wall, cytoplasm or nucleus
Do cells possess receptors for all hormones?
no
Is it possible for a single hormone to have multiple receptors?
yes, i.e., CCK has a receptor on the pancreas an a receptor in the brain
The distribution of the hormone or the hormone receptor determines which cells respond?
distribution of the hormone receptor
Are hormone receptors limited to one cell type or are they distributed on most cells?
It can be one or the other depending on the hormone receptor
Binds and exerts biological effect similar ot hormone
agonist
binds and exhibits a supraphysiological response
superagonist
binds and produces a subphysiological response
partial agonist
Binds to receptor but does not activate it(no physiological response)
antagonist
Most cells in the body have receptors for what specfic hormone?
insulin
High specificity between hormone receptor and ligand is characterized by what?
homologous binding but not perfect
High affinity for hormone receptor and ligand is characterized by what?(2 points)
adequate binding at low hormone concentrations
Affinity for a partcicular hormone compared to affinity for another hormone determines what hormone receptor-ligand property?
specificity
Under normal circumstances, it is possbiel to gain a response from a hormone without the presence of a hormone receptor?
no
The structure and location of the receptor depends on what?
the structure of the hormone
Peptide/protein hormones have receptors located on what cellular/subcellualr structure?
cell surface
Steroid/lipid hormones have receptors located on what subcellular structure?(2 points)
cytoplasmic or nuclear receptors
When the hormone receptor has a high affinity for the hormone, the disassociation for the hormone and the hormone receptor should be slow or fast?
slow
Generally speaking, neurotranssmiters and their receptors have high afinity or low affinity? How is this compensated?
The afinity is low, therefore, a large amount of neurotransmitteres are released to elicit a response.
Hormone receptors that have affinity for their hormones, when the concentrations are abnormally high, what happens with the binding of that hormone?
The hormones may bind to “wrong” receptors despite the low affinity
The preference for a hormone receptor to bind to its respective hormone is referred to as what?
specificity
What is the number of hormone binding sites for protein hormones?
at least one
The binding between the protein hormones and their respective receptors are reversible or irreversible?
their reversible, non-covalent
What target tissue has a constant amount of receptor numbers?
none
What is a general example of homeospecific regulation of a hormone receptor?
the hormone regulated the amount of respecitve hormone receptor for it to bind
What is a general example of heterospecific hormone receptor regulation?
A hormone regulated the amount of available receptors for another hormone besdies itself
What is the up-regulation of a paricular receptor?
an increase in receptor number
What is the down-regulation of receptor number?
a decrease in receptor number
How does prolactin affect the PRL receptor in the liver?
Prolactin induces the appearance of PRl receptor in the liver, an example of positive feedback
How does the continuous exposure of insulin to lymphocytes affect the number of insulin receptors?
it decreases the nubmer of insulin receptors (negative feedback)
What is an example of homeospecific regulation of receptor number?(2 points)
GnRH downregulates or upregulated GnRH repcetors depending on timing
What is an example of hetrospecific regulation of receptor number?(2 points)
TRH stimulates the release of TSH which stimualtes the synthesis and secretion of T3 and T4 which can return and cause a decrease of receptors for TRH
Do glucocorticoids upreguate or downregulate TRH receptors?
up-regulate
What hormone always downregulates its receptors irrespective of tissue?
insulin
What is an example of a hormone that upregulates and downregulates it receptor depending on the location in the body?
Angiotensin II upregulates its own receptors in the adrenal but down-regulates receptors on certain smooth muscles
What are examples of ways that downregulation of receptors take place?(2-5 points)
inactivation of receptor molecules perhaps by phosphorylation. Inactivation of intracellular protein signaling molecules. Temporary sequestration of receptor inside cell. Destruction of receptors by lysosomal enzymes after internalization. Decreased production of new receptors.
How does up-regulation occur?(2-3 points)
increased synthesis of receptors, increased synthesis of intracellular signaling molecules and increased availability of receptors at hte cell surface
Why change receptor number?(2-3 points)
Prevents over-stimulation, prevent organ burn-out and allows for orderly sequencing of various hormonal secretions
Must all hormone receptors be occupid by hormone receptor to elicit a response?
no, all of the receptors don’t have to be occupid to elicit a response
The receptor number influences what?
it influences the hormonal response
What is the typical percentage of receptors that must be occupid by hormones to be sufficient for maximal biological response?
1%
What is the reason for spare receptors?
Maintain a stable sensitivity to low levels of hormone
Are spare receptors biologically active?
yes
Epinephrine and glucagon both stimulate what in liver cells?
glycogenolysis
Epinephrine and glucagon act via what common second messenger?
cAMP
What common receptor does epineprine and glucagon bind at the liver?
they don’t have a common receptor, each hormone has its own receptor
Hormone response depends on what?(3-6 points)
receptor number, hormone concentration, duration of exposure, time between exposures, intracellular conditions, synergestic/antagonistic hormones
The duration of exposure for the hormone to the hormone receptor is influenced by what?(2-3 points)
rate of hormone secretion, half-life of the hormone and clearance of the hormone
receptor desensitization
What is the difference between responsivity and sensitivity?
Does changes in responsivity result in changes of ED50?
no
Does changes in sensitivity result in changes in ED50?
no
Changes in responsivity happens as a result of what being changed?(2-3 points)
More/few receptors, changes in the rate-limiting step of the receptor pathway and more/less tissue,cells
Does responsivity result in a change in the maximal response?
yes
Does sensitivity change the maximal response?
no
Changes in sensitivity occurs as a result of what?(1-2 point)
changes in affinity and changes in hormone receptor number when you have submaximal concentration of hormone is present
What are the four classes of membrane boud receptors?
receptors that are enzymes or are enzymes linked, receptors that form channels, g-protein couples receptors and receptors with unknown mechanisms
Most peptide hormone receptors are coupled to what?
G-proteins
What are the different type of G-proteins coupled to membrane receptors?(2 points)
stimulatory and inhibitory
When a hormone binds to a Gαreceptor, what are the general steps that take place with the second messengers?(6 points)
Phopholipase C is activated which hydrolyrzes phosphoinositol 4,5 bisphosphate into IP3 and DAG. IP3 diffuses to intracellular calcium stors and indcues the relase of calcium by bind to calcium channel-linked IP3 receptors. DAG is lipophilic and remains in the plasma membrane and activats protein kinase C.
Physiological communication takes place via what major systems in the body?(3 points)
hormonal, neural and immune
Negative or positive feedback reuglation can take place via what general substances?(2 points)
Hormones or the substrates in the respective pathways
What are general examples of neural regulation?(2-3 points)
hypothalamo-neurohypophyseal system, adrenal medulla, hypothalamoadrenohypophyseal end organ axis
What are four examples of hormonal regulation?
negative(positive) feedback reuglation, chronotropic regulation, neural regulation and stress
What are examples of chronotropic regulation?(3-7 points)
oscillating, pulsatile, circadian/diurnal, sleep-wae, menstrual, seasonal and developmental
What are the types of neural hormonal regulation?(2 points)
direct or indirect
The hypothalamo-adenophypophyseal end organ axis is an example of direct neural hormonal control or indirect neural hormonal control?
indirect
The hypothalamo-neurohypophyseal system is an example of direct neural hormonal control or indirect neural hormonal control?
direct
What are examples of direct neural hormonal control?(1-2 points)
The synthesis of ADH or oxytocin with storage and release from the poserior pituitary initiating affects in the renal tubules or the reproductive system. The actions at the adrenal medulla are also under direct neural hormonal control.
What is an example of indirect neural hormonal regulation?
The hypothalamus influencing the anterior pitutiary to release a hormone to affect a particular target tissue
What are the types of substrate regulation?
indirect and direct
What are examples of direct substarte control?(2 points)
The release or PTH or calcitonin in response to calcium levels. PTH is release to increase calcium levels while calcitonin is release to decrease calcium levels. Also, the release of insulin, glucagon and somatostatin in response to glucose levels. Insulin is relased to decrease glucose levels and glucagon is release to increase glucose levels. Somatosatin inhibits the action of both.
What is an example of indirect substrate control?
Sodium influences the release of aldodster indirectly by conveying a decrease supply of sodium at the mecula densa stimulating the renin-angiotensin system which results in the conversion of angiotensinogen to angiotensin I which is converted to angiotensin II in the liver. Angiotensin II stimulates the production of aldosterone at the zona glomerulosa which vasoconstricts the blood vessels resulting in an increase in blood pressure.
What is the reason for short loops and long loops when studying negative feedback loops in the endocrine system?
What are teh two major categories of endocrine dysfunction?
hypofunction or hyperfunction
How are endocrine dysfunction pathologies categorized in either hypofunction disease states or hyperfunction disease states?(4 points)
primary, secondary, autoimmune or receptor abnormalities
A primary endocrine dysfunction usually has some type of pathology at the endocrine disorder in question or an organ outside of the endocrine organ in question?
There is usually a problem with the endocrine organ in question.
A secondary endocrine dysfunction has a problem with the endocrine organ in question or an endocrine organ/target organ besides the endocrine organ in question?
There is usually a problem with the target organ/endocrine organ outside of the endocrine organ in question
Transient autoimmunity is usually in response to what genearl circumstance?
infection
Chronic autoimmunity is usually a result of what?
a pathological consequence
What autoimmune disorder occurs in Graves disease and how does this affect hormone production?
Antibodies stimulate the production of TSH in Grave’s disease
What type of autoimmune disorder occurs in Hashimoto’s thyroiditis?
Antibody produced in teh body target enzymes within the thyroid cell which results in the destruction of thyroid cells.
What is an example of antibody-mediated disease?
Graves disease
What is an example of a T-cell mediated disease?
Hashimoto’s thyroiditis
What is an example of an immune complex mediated diseae?
Systemic Lupus erythematosus
If a pregnant woman is affected with Graves disease, is it possible for the child to manifest symptoms related to thyroiditis?
Yes, the IgG antibodies can cross the placenta
What is the pathophysiology of a patient affected with Hashimoto’s thyroiditis?
Autoreactive T cells produce cytokines that recruit cytotoxic T cells and macrophages to destroy follicular T cells. Paradoxcially, this can initlaly result in hyperthyroidism due to the fact that the linkage between the storage of the thyroid horones, in the colloid, and the follicular cells, there will be an initla increase of thyroid hormones beucase the thyroid hormones will leak out.
The pathology of immune complex disease is characterized by what?
the production of autoantibodies that circulate the bloodstream. A major pathology as the result of these complexes is the deposition of these complexes in small areas of the body like the glomeruli in the kidneys or joints spaces resulting in kidney failure and joint pain.
What gender is more likely to have autoimmunity disorder?
female
What are possible triggers of autoimmunity?(2-4 points)
Release of sequestered antigens as a result of truama, infections, neoantigens and shared/cross-reactive antigens
What are the two categories that autoimmunity can affect the body?
systemic and organ specific
What are examples of organ specfic autoimmuity diseases in the endocrine sysetm?(4 points)
**Hashimoto’s thyroiditis, addison’s disease, Graves disease and insulin dependent diabetes mellitus **
What are exampels of systemic autoimmune disorders?(3 points)
Rheumatoid arthritis, scleroderma and systemic lupus erythrematosus
What are hte general types of polyglandular disorders?
Type I, type II and type III
Excessive hormone production is usually caused by what general type of pathology?
neoplasia
Medullary Carcionma tumor in the thyroid gland produces what hormone in excess?
calcitonin
Polyglandular disease is usually the consequence of what genearl type of pathology?
autoimmune disorders
What is the type of polyglandular disorder: Type I, II or III: usuallly diabetes or thyroid disease and Addison’s disease, sometimes ovarian failure and non-endocrine autoimmune disease
type II
What is the type of polyglandular disease: onset in early childhood (skin infection) associated with hypoparathyroidism and Addisons’s, often gonadal failure
type I
What is the type of polyglandular disease: thyroid and autoimmune disease and at least two other autoimmune disease, but NOT Addison’s disease
type III
Does polyglandular diseases reuslt from neoplastic issues or autoimmunity issues?
autoimmunity
What are examples of autoimmune disease that affected the thyroid gland?(2 points)
hashimoto’s and graves
What is an example of an autoimmune diseae that affects that adrenal gland?
addison’s disease
What is an example of an autoimmune disease that affects the pancreas?
insulin dependent diabetes mellitus
What is an example of an autoimmune disease that affects the parathyroid gland?
hypoparathyroid
What is an example of an autoimmune disease that affects the pituitary gland?
hypophysitis
What is an example of an autoimmune disease that affects the ovaries?
oophoritis
What is an example of an autoimmune disease that affects the testes?
orchitis
