Basics of Endocrinology I Flashcards
What is the defining feature of classic endocrine glands?
They are ductless!
Where do the secrete hormones?
Directly into the blood or extracellular spaces
What are the non-classical endocrine glands?
Brain (esp. hypothalamus), Kidneys, Heart, Liver, GI, Adipose Tissue
What is the endocrine function of the the brain?
“releasing hormones”
What is the endocrine function of the kidneys??
Release of renin, Vit. D, EPO
What is the endocrine function of the heart?
release of ANP/BNP
What is the endocrine function of the liver?
Release of IGF-1 (insulin like growth factor-1)
What is the endocrine function of GI tissue?
stomach, small GI release serotonin, ghrelin
what is the endocrine function of adipose tissue?
Release of leptin
Discuss the concept of homeostasis in regards to hormones
There is a balance of hormones in the body - hormones are always present, in a regulated amount. Too much or too little of a given hormone can cause problems
What can give a hyper response to a hormone?
Too much of the hormone or too much of the hormone receptor
What can give a hypo response?
Too little hormone or too little receptor
What are endocrine pathologies characterized by?
A hormone imbalance
Where can the defect be in an endocrine pathology?
At the level of the gland –> primary
One or two steps away –> secondary/tertiary
Give an example of and describe an endocrine pathology that is congenital
Cretinism: due to an iodine deficiency during development
results in: short stature, mental retardation, delayed motor development
Give an example of and describe an endocrine pathology that is genetic
Multiple Endocrine Neoplasia (MEN): Characterized by 2-3 tumors in multiple endocrine glands (parathyroid, pituitary, entero-pancreatic)
Give an example of and describe an endocrine pathology that can give rise to malignant or benign tumors
Neoplastic tissues, small lung cell carcinoma
Give an example of and describe an endocrine pathology stemming from an infection/immunological problem
autoimmune - Diabetes type I
Give an example of and describe an endocrine pathology stemming from environmental factors
PCBs, DES, birth control
Give an example of and describe en endocrine pathology stemming from trauma/stress
Sheehan’s syndrome: postpartum hemorrhage and shock - results in massive pituitary death
Give an example of and describe an endocrine pathology related to surgery
Thyroid gland removal (often parathyroid injury)
Give an example of and describe an endocrine pathology stemming from a therapy
Glucocorticoids (Crohn’s disease, others)
What is the most common endocrine pathology, and what are some important facts about it?
Type II diabetes!
7th leading cause of death
affects 9.3% of population (2 mil new cases per year)
highly correlated with obesity
Define endocrine action
Hormone release into the blood, acting on downstream tissue
Define paracrine action
Hormone released into the interstitial space, acting on nearby cells
Define autocrine action
Hormone released into the interstitial space that will act on the same cell that released it
Discuss some differences in the regulation of hormone action between endocrine and paracrine signaling in regards to the source and distribution of the hormone
Source:
endocrine - gland, no specificity to target
paracrine - adjacent cell, major determinant of target
Distribution:
Endocrine - Universal, dilution big
Paracrine - ECM, binding proteins, diffusion distance, proteases
What are things to consider regarding the signal being passed to the target cell?
specificity/sensitivity, # of receptors, downstream pathways, metabolism of receptors, other ligands, inhibitory pathways, etc.
What class of hormones are usually attached to hormone binding proteins in the blood?
Steroids
What are the hormones other than steroids that bind to hormone binding proteins?
IGF-1, GH, T4/T3
What is the purpose of hormone binding proteins?
Increases the half life of the hormone
What is a pharmacological consequence of hormone binding proteins?
Bound hormones are not active and as some are released right at the target site, you may not see any measurable free/active hormone in the blood
What does sex hormone binding globulin (SHBG) bind?
estrogens and testosterone
What does corticosteroid binding globulin (CBG) bind?
cortisol and corticosterone
What does thyroxine binding globulin (TBG) and transthyretin (TTR) bind?
thyroid hormone
What does albumin bind?
most lipophilic compounds in blood
What is notable about hormones bound to albumin?
They are bioavailable!
Discuss the two methods of hormone delivery to their target
The hormone can be released at the cell surface, translocate the plasma membrane, and exert its effect on the cell
Or, the hormone/protein complex binds to megalin, there is the formation of an endocytic vesicle, after which the hormone will dissociate and e released from the vesicle
Why would a cell undergo the vesicle delivery of hormone?
The vesicle could be targeted to a specific part of the cell
Protects the hormone from degradation
Describe some features of hormone receptors
no receptor = no action (antagonist, agonist)
determines duration: extracellular receptors are internalized and dissociated, internal receptors are ubiquinated
autoregulation by ligand: up/down regulated based on ligand levels
With what specificity and affinity do hormones bind their receptors?
High affinity and high specificity
Define specificity
ability to distinguish between similar substances
Define affinity
How much a receptor will hold on to a ligand once bound
measured as Kd: ligand concentration at which 50% of binding sites are filled (smaller number = higher affinity)
Ki: ability to displace ligand at 50% maximal activity
What are some general features of lipophobic receptors, and what are the different classes?
Bind to cell surface receptors
coupled to second messenger pathways like cAMP, IP3, DAG
rapid internalization/degradation
Classes:
1: Ion channels
2: G-protein coupled
3: Receptor-linked Kinases
4: Receptor Kinases
Discuss the features and function of cell surface class 1 ion channels
binding of ligand causes conformational change that results in opening of channel
Neurotransmitters typically activate these types of receptors
Discuss the features and functions of cell surface class 2 G-protein coupled receptors
Most protein and peptide hormones bind to this kind of receptors
Ligand binding activates second messenger signaling cascades
Discuss the features and functions of cell surface class 3 receptor-linked kinases
DO NOT have intrinsic catalytic activity
Ligand binding results in dimerization, activates the intracellular kinase
examples: GH, prolactin, EPO
Discuss the features and functions of cell surface class 4 receptor kinases
Have intrinsic catalytic activity that is stimulated by ligand binding - autophosphorylation on intracellular domain
Insulin and atrial natriuretic peptide bind to this kind of receptor
What are some general functions of lipophilic hormone receptors
Bind mainly to intracellular receptors
often attached to large chaperone proteins in the cytoplasm (heat shock proteins)
usually slow biological response - requires transcription/translation
can repress or activate transcription
What is an example of a lipophilic hormone?
Thyroid hormone binds nuclear receptor, when receptor binds ligand there is gene activation
What are the factors affecting hormone bioavailability?
Hormone transport: binding proteins and kinetics
Target tissues: receptor regulation and chaperone/heat shock proteins
Hormone synthesis/release: enzymatic activity and processing/packaging
Regulatory mechanisms: eedback, circadian rhythms, aging, pulsatility, metabolism/degradation
