Lecture 1: Basics Flashcards
True or false: classical endocrine glands are ductless?
True (secrete hormones directly into bloodstream or extracellular space)
What are the non-classical endocrine organs?
1) Brain (hypothalamus)
2) Kidney (renin, erythropoietin, vitamin D)
3) Heart (ANP, BNP)
4) Liver (IGF-1)
5) GI (serotonin, ghrelin)
6) Adipose tissue (leptin)
What is the largest upstream endocrine upregulator?
Hypothalamus
Definition of homeostasis
state of equilibrium/balance in the body with respect to various functions and to chemical compositions of fluids and tissues
What immune organ is responsible for integrating the many endocrine signals from the body?
thymus
What does the target cell response to hormone depend on?
the ratio of receptors present in the cell
What are some of the etiologies of endocrine disorders?
1) Congenital
2) Genetic
3) Trauma/stress
4) Surgical
5) Therapeutic
6) Tumors
7) Infections
8) Autoimmune
9) Environmental
What is an example of a congenital endocrine pathology?
Cretinism
iodine deficiency during development
What is an example of a genetic endocrine pathology?
MEN (Multiple Endocrine Neoplasia)
2-3 tumors in multiple endocrine glands (pituitary, parathyroid, entero-pancreatic)
What is an example of a genetic endocrine pathology?
MEN (Multiple Endocrine Neoplasia)
2-3 tumors in multiple endocrine glands (pituitary, parathyroid, entero-pancreatic)
Example of tumor induced endocrine pathology?
small lung cell carcinoma
Example of immunological endocrine pathology?
autoimmune (DMII)
Example of environmental endocrine pathology?
birth control
Example of trauma/stress induced endocrine pathology?
Sheehan’s Syndrome
Example of surgical endocrine pathology?
thyroid removal
Example of the therapeutic endocrine pathody?
glucocorticoid therapy (Crohn’s disease)
Define autocrine signaling
hormones secreted into the interstitial space acting back on the same cell
Define paracrine signaling
hormones secreted into the interstitial space acting at nearby cells
How are hormones transported in the blood?
Via hormone binding proteins (bind to hormones in the blood to facilitate transport)
What is the benefit of hormone binding proteins?
increases the half life of the hormone
What is more commonly bound to hormone binding proteins, steroid or peptide hormones?
steroid (lipophilic)
In addition to steroid hormones, what other hormones use hormone binding proteins?
IGF-1
GH
T4/T3
What are the 3 highly specific hormone binding proteins?
1) SHBG (Sex hormone binding globulin) - binds estrogen and testosterone
2) CBG (corticosteroid binding globulin) - binds cortisol/corticosterone
3) TBG (thyroxine binding globulin) and TTR (transthyretin) - binds thyroid hormone
What is the only non specific hormone binding protein?
albumin (binds most lipophilic compounds in the blood)
Weak interaction
What is the definition of bioavailable hormone?
unbound + albumin bound
Is most hormone bound or unbound?
BOUND
Do women or men have more SHBG bound hormone?
Women (70%. Men have 30-45%)
Men have more bioavailable testosterone
Is bioavailable hormone free hormone?
No, only unbound protein is free
albumin bound is bioavailable
What is the only non specific hormone binding protein? (also binds the most lipophilic compounds in the blood)
albumin (binds most lipophilic compounds in the blood)
Weak interaction
Is bioavailable hormone free hormone?
No, only unbound protein is free
albumin bound is bioavailable
What percentage of hormone is unbound in the blood?
0.5-3%
How do steroid hormones cross the membrane?
undock from their carrier, diffuse across the membrane and finds intracellular targets
How do steroid hormones cross the membrane in the conventional way?
undock from their carrier, diffuse across the membrane and finds intracellular targets
What is the second, newer theory for how steroid hormones enter the cell?
bind to Megalin on the plasma membrane which then engulfs it into an endocytic vesicle
How are hormone responses regulated?
autoregulation by ligand (quantity of ligand) or quantity of receptors (cell surface and intracellular)
hormones bind receptors with ______ specificity and ______ affinity
HIGH and HIGH
Define specificity in terms of hormones
ability to distinguish between similar substances
Define affinity
Kd (ligand concentration that occupies 50% of binding sites)
What is Ki?
ability to displace ligand at 50% max activity
The smaller the Kd, the ___________ the affinity
HIGHER (need fewer hormones to saturate 50% of receptors)
Which has greater affinity for receptor? hormones bound to specific or non-specific binding proteins?
SPECIFIC
What is the difference between lipophobic and lipophilic receptors?
lipophobic: Cell surface
lipophilic: intracellular
What are some examples of lipophobic receptors?
1) Ion channels
2) G protein coupled
3) Receptor tyrosine kinases
4) receptor kinases
Which receptors have SLOW responses, lipophobic or lipophilic?
LIPOPHILIC –> requires transcriptional/translational events (can repress or activate)
What is an example of lipophilic receptor?
thyroid hormone nuclear receptor
NOT bound to ligand = transcriptional repression
Most proteins and peptide hormones bind what kind of receptor?
G protein coupled
Which class of cell surface receptors do NOT have intrinsic catalytic activity?
RTKs
What 3 hormones use RTKs?
1) Growth hormone
2) Prolactin
3) Erythropoietin
What class of receptor do insulin and ANP use?
receptor kinases
What are 4 things that affect hormone bioavailability?
1) Hormone transport
2) Target tissue
3) Hormone synthesis/release
4) Regulatory mechanisms
