71 - Basics Flashcards
What are the 3 major characteristics of a “classic” endocrine gland?
- Ductless
- Secrete hormones directly into the bloodstream or extracellular space
- The organ is dedicated primarily to endocrine function
What are some e.g.’s of non-classical endocrine organs?
- Brain (hypothalamus especially)
- Kidney (renin, vit. D, EPO)
- Heart (ANP, BNP)
- Liver (IGF-1)
- GI: stomach/small intestine (5-HT, ghrelin)
- Adipose tissue (leptin)
Define homeostasis as it relates to the endocrine system.
The state of equilibrium (balance between opposing measures) in the body w/r/t various functions and to the chemical compositions of the fluids and tissues
In endocrine homeostasis, discuss the concept of “hyper”.
Overproduction of a hormone and/or hypersensitivity to its hormonal affects.
In endocrine homeostasis, discuss the concept of “hypo”.
Underproduction of a hormone and/or insensitivity to its hormonal affects.
In endocrine pathology, primary defects affect a ____________ endocrine gland.
Classical
If an endocrine pathology doesn’t affect a classical gland, it’s either a ________ or _______ defect.
Secondary or teritary
What’s the etiological category of cretinism?
iodine deficiency, most common cause of retardation world-wide
Congenital
What’s the different b/w congenital and genetic?
Congenital: present at birth; not necessarily genetic
What’s the etiological category of multiple endocrine neoplasia (MEN)?
(multiple endocrine glands have tumors)
Genetic
What’s the etiological category of environmental factors such as PCBs, DES, and/or BCP?
Endocrine disruptors
What’s the etiological category of Sheehan’s syndrome?
postpartum hemorrhage/shock; results in massive pituitary cell death
Trauma/stress
What’s the etiological category of thyroidectomy?
Surgical
What’s the etiological category of glucocorticoid therapy?
e.g. Chrohn’s disease, etc.
Therapeutic
What’s the etiological category of neoplastic tumors or small lung cell carcinoma?
(SCLC: cancer not in an endocrine gland, but secretes hormones typically released by the pituitary)
Malignant and benign tumors
What’s the etiological category of T1DM?
Infections/immunological problems (Autoimmune, in T1DM)
Distinguish amongst endocrine, paracrine, and autocrine.
- Endo: hormones secreted into blood, act on downstream targets
- Para: hormones secreted into ISF, act on nearby cells
- Auto: hormones secreted into ISF, act back on same cell
Neurotransmission is a type of (endo/para/auto-crine) signaling.
Paracrine
Endo vs. paracrine:
- Which signaling has more specificity of target?
- Which has a greater importance on receptors for specificity?
- Which must be released in greater concentration?
- Paracrine
- Endocrine (travels farther)
- Endocrine (gets diluted)
Which are biologically active: free hormones, bound hormones, or both?
Free hormones only
What major class of hormones uses binding proteins most often for xport?
Steroid hormones (lipophilic)
Do binding proteins change the 1/2-life of their bound hormone?
Yes, increase 1/2-life
What’s the major nonspecific binding protein?
Albumin
What’s the binding protein for estrogens and testosterone?
Sex hormone binding globulin (SHBG)
What’s the binding protein for cortisol and corticosterone?
Corticotrophin binding globulin (CBG)
What are the 2 binding proteins for TH?
- Thyroid binding globulin (TBG)
- Transthyretin (TTR)
Is most hormone in the blood bound or unbound?
Almost all bound
When hormones are bound to albumin they’re not considered bioactive but they are considered bio-___________.
available (pretty to use hormone bound to albumin if you need to)
What are the 3 steps of the old model for hormone delivery to target cell? (just read)
- Steroid hormone released at membrane
- Freely diffuses across lipid bilayer
- Finds extracellular target
*What are the 3 steps of the new model for hormone delivery to target cell?
- Hormone/protein complex binds to megalin
- Formation of endocytic vesicle
- Hormone dissociates and is released from vesicle
According to wikipedia, what are the effects of ubiquitination?
- Can signal for ptn degradation via the proteasome
- Can alter ptn cellular location
- Can affect ptn activity
- Can promote or prevent protein interactions
*What are 3 major categories by which a protein receptor can be regulated?
(just read at first)
- Agonists/antagonists
- Affect hormone duration: internalization/dissociation/ubiquitination
- Ligand (hormone) autoregulation
Hormones bind receptors w/____ specificity and ____ affinity.
High, high
Define specificity.
Ability to distinguish b/w similar substances
Define Kd (same as Km). What is the relationship b/w Kd and affinity?
Ligand conc. that occupies 50% of the binding sites
- Inverse relationship w/affinity
Define Ki.
Ability to displace ligand at 50% of maximum activity
- How much of something else do I need to add before I can knock it off?
*What are the characteristics of lipoPHOBIC hormone receptors?
- Bind to cell surface receptors
- Coupled to 2nd messenger signaling pw’s including: cAMP, IP3/DAG
- Rapid internalization or degradation
*What are 3 eg’s of lipophobic hormone receptor classes?
- GPCRs (most)
- Receptor-linked kinases = GH, PRL, EPO.
- Receptor kinases = insulin, ANP
*What are the characteristics of lipoPHILIC hormone receptors?
- Bind mainly to intracellular receptors (some exceptions).
- Often bound to large chaperone proteins in cytoplasm (often heat shock proteins)
- Usually SLOW biological response – requires TS/TL events.
- Can repress or activate transcription.
*Does TH bind a lipophilic or lipophobic receptor?
Discuss its somewhat unique properties.
Lipophobic
- THs bind nuclear steroid receptors (superfamily even tho they’re not steroid hormones)
- When receptor is NOT bound to ligand = transcriptional repression. Ligand (TH) binding activates gene TH.
What type of cell surface receptors do peptide/protein hormones typically bind?
GPCR (activate 2nd msger)
How does a Receptor-Linked Kinase hormone receptor function?
Do they have intrinsic catalytic activity?
Ligand binding causes dimer formation – activates intracellular kinase
- DO NOT have intrinsic catalytic activity
(GH, PRL, EPO)
Do Receptor Kinases have intrinsic catalytic activity?
Yes
Insulin, ANP
Factors affecting hormone bioavailability? (read)
Hormone Transport:
- Binding proteins – “free” vs bound
- Kinetics: half-life
Target Tissues:
- Receptors – mutations, desensitization, down/upregulation,
- Chaperone/Heat shock proteins
Hormone synthesis/release:
- Enzymatic activity
- Processing/Packaging
Regulatory mechanisms:
- Feedback
- Circadian rhythms
- Aging
- Pulsatility
- Metabolism/Degradation
