General Endocrine Flashcards
What are the functions of the endocrine system?
regulate: energy breakdown and storage, reproduction sexual and gamete development and behavior, growth-proliferation, differentiation, and skeletal, and internal milieu- composition of body fluids, electrolytes, acid-base, and glucose
What are the multifactorial aspects of regulation in the endocrine system?
a hormone can regulate multiple functions and each function can be controlled by several hormones
What are the four major classes of hormone precursor molecules?
protein, cholesterol, AA and FA
What can protein precursors become when deriving hormones? examples of each.
protein- GH, FSH, LH (LH and FSH are 2 polypeptides); Cleave or processed peptide- ACTH, ADH, PTH, and oxytocin; AA cleavage for thyroid hormones T3 and T4
What can AA precursors become when deriving hormones? examples of each.
tripeptide-TRH and modified AA- NE and Epi
What can Cholesterol precursors become when deriving hormones? examples.
steroid- cortisol, androgens, and estrogens
What can FA precursors become when deriving hormones? examples
retinoids, Vit D3, Eicosanoids - 1-25OH Vit D3 and Prostagandins
What is a endocrine gland?
conglomeration of source cells that produce a specific hormone
How are hormones effects limited to target cells?
target cells respond because they have the receptor for the hormone, cells without the receptor are unaffected directly, hormone must come in direct physical contact with target cell receptor
Where are receptors located for hormones?
polypeptide hormone receptors on cell surface; steroid hormone receptors either cytoplasm or in nucleus
How are hormones transported?
through the blood; steroids are bound to a protein
What are the salient features of hormones and their target cells?
binding is saturable and reversible, use second messengers, response elicited determined by target cell and not type of second messenger, can only slow or speed up an existing process not create a new process, rarely process sensitive to only one hormone, hormones usually have multiple actions in multiple sites
Why have input from multiple hormones?
redundancy of function, safety net, ensures maintenance of internal environment under diverse conditions (homeostasis)
The same precursor can be used for different hormones. How is this achieved?
the enzymes in the different glands break the precursor molecule up differently
What is the function of hormone binding globulins?
bind while circulating in plasma; increase half life and assure uninterrupted delivery, no function while bound free hormone (active form) binds to receptor and is in equilibrium with hormones bound to globulins so they are released upon demand; synthesized mostly in the liver
What happens to a hormone after binding to a receptor and eliciting response?
action terminated, metabolized to give additional precusors to produce more hormones for local or systemic actions, selectively degraded to prevent local action or metabolized to inactive forms that are eliminated
In breakdown of hormones, what is the difference between peptide and steroid?
peptide- bind to receptor, endocytosed and degraded in a lysosome; steroid- metabolized to inactive analogs or converted to water soluble forms for secretion
What is the difference between steroids/thyroids and peptides and catecholamines in storage capability?
S/T-minimal except thyroids; P/C-Yes
What is the difference between steroids/thyroids and peptides and catecholamines in binding proteins?
S/T- always; P/C- uncommon
What is the difference between steroids/thyroids and peptides and catecholamines in half life?
S/T- Long hours to days; P/C- short minutes
What is the difference between steroids/thyroids and peptides and catecholamines in action mechanism?
S/T- direct, no second messenger, transcriptional; P/C- indirect, second messengers, transcriptional and translational
What are the classes of polypeptide receptors?
GPCR and enzyme-linked (dimerization; activates intrinsic kinase or recruits and activates associated kinase)
What is the function of the alpha subunit in Gs? Gi? Gq?
Gs- activates andenylate cyclase; Gi- inhibits cyclase, Gq- activates phospholipase Cbeta
After being activated by alpha subunit of the Gq GPCR what does phospholipase C do?
cleave PIP2 to DAG and IP3; then DAG and Ca activate PKCwhich is recruited to plasma membrane
What do GKR and arrestin do?
GRK phosphorylates only activated GPCR because it is activated by GPCR; arrestin binds to phosphorylated GPCR and prevents its binding to G protein and induces endocytosis
What are the three distinct domains of polypeptide intracellular receptors? function?
AF-1 (activation function) domain at amino terminus and AF2 at carboxy terminus which activate transcription; DBD (DNA binding domain) bind specific DNA motifs; LBD (ligand binding domain) binds the hormone, CoA and CoR- coactivators and suppressors that modify transcription rate
What are two important domains in intracellular receptors other than the distinct domains?
NLS- nuclear localization sequence, targets protein to the nucleus; DMD- dimerization domain, links two receptors together for DNA binding
What are the differences between heterodimeric and homodimeric intracellular receptors?
homo- binds hormone in the cytoplasm, idle receptor kept in inactive state by inhibitors bound to hormone binding site which are dissociated by the hormone, use NLS to translocate to nucleus; hetero- are in the nucleus, not understood how they are kept idle
What are examples of homodimeric receptors?
estrogen, progesterone, androgen, glucocorticoid, and mineralocorticoid
What are examples of heterodimeric receptors?
thyroid, retinoic acid and Vitamin D
In the example of estrogen receptors how does the co-repressor keep it in an inactivated state?
CoR recruits HDAC (histone deacetylases) which maintain histones in a deacetylated state which favors chromatin condensation
How does estrogen binding cause activation of the receptor and transcription?
results in a conformational change in AF2 that facilitates interaction with CoA which bind HAT (histone acetyltranferase); acetylation of histones leads to chromatin decondensation facilitating transcriptional activation; AF1 and AF2 activate transcription independently or synergistically
What are three ways or places affected that cause hormone resistance can occur?
abnormal hormone, receptor defect, post receptor mechanism
What hormones receptors are known to have genetic defects that destroy either receptor specificity or receptor binding?
glucocorticoids, T3 and T4, DHT, Vitamin D3, ADH, GH and TSH
What are the different places/mechanisms that can cause hypofunction of a hormone?
destruction or block at the gland, block from prohormone to hormone, stimulation of degradation process (decreasing 1/2 life), antibodies and antagonists affecting receptors, defect in receptor, effector system or response, or tissue damage effecting the response
What are the different places/mechanisms that can cause hyperfunction of a hormone?
tumor or hyperplasia at the gland, ectopic production or Iatrogenic of prohormone or hormone, block of degradation (increasing half life), antibodies/agonists stimulating receptors, stimulation of receptor, effector or response element, and tissue damage like precursor of response in excess
What are examples of conditions of caused by hypofunction due to destruction of endocrine glands?
autoimmune disease; type I diabetes, hypothyroidism, adrenal insufficiency, gonadal failure
What are examples of conditions of caused by hypofunction due to extra-glandular disorders?
effecting absorption and metabolism of hormone; defective conversion of 25D3 to 1,25 D3; deficiency of 5alpha-reductase resulting in impaired DHT from T
What are examples of conditions of caused by hypofunction due to specific defects in hormone biosynthesis and transport?
21-hydroxylase deficiency syndrome causing defective cortisol production, dietary iodine deficiency results in deficient thyroid hormone biosynhtesis
What are examples of conditions of caused by hyperfunction due to endocrine tumors?
pituitary causing overproduction of ACTH, GH, PRL, TSH, LF, FSH
What are examples of conditions of caused by hyperfunction due to ectopic tumor?
tumors produce hormones (ACTH, ADH and calcitonin)
What are examples of conditions of caused by hyperfunction due to anti-receptor antibodies?
autoimmune stimulation results in production of antibodies that stimulate TSH receptor causing hyperthyroidism
What is TRH?
thyrotopin releasing hormone
What is CRH?
corticotropin releasing hormone
What is GHRH?
growth hormone releasing hormone
What is GnRH?
gonadotropin releasing hormone
What is SS?
somatostatin
What is TSH?
thyroid stimulating hormone
What is ACTH?
adrenocorticotropic hormone
What is PRL?
Prolactin
What is GH?
growth hormone
What is FSH?
follicle stimulating hormone
What is LH?
luteininzing hormone
What is DHT
dihydro-testosterone
What is ER?
estrogen
What is T?
testosterone
What is T3 and T4?
thyroid hormones
What types of control are endocrine glands under?
most neuroendocrine, some metabolic (by metabolite)
What effect does CNS play with endocrine system?
endocrine can affect CNS (mood, anxiety, or behavior); CNS controls release of master hormones (releasing hormones) from hypothalamus these can be stimulatory or inhibitory
What do releasing hormones do?
stimulate or inhibit the secretion of tropic hormones from the pituitary which cause the release of organ/target hormones or ultimate hormones
What do target hormones do?
act on target cells throughout the body; exert feedback control on hypothalamus and pituitary (usually negative) or metabolite from target cells feeds back on the gland itself
