1 - Principles of Endocrinology Flashcards
What are the functions of the endocrine system?
To coordinate and integrate cellular activity within the whole body by regulating cellular and organ function throughout life and maintaining homeostasis
- Regulate sodium and water balance
- Regulate calcium and phosphate balance
- Regulate energy balance
- Coordinate stress response
- Regulate reproduction, development, growth and senescence
What are the three components of the endocrine system?
1 - Endocrine glands
2 - Hormones
3 - Target organs
Describe endocrine glands
- No anatomical connection
- Ductless glands
Coordination of glands that are NOT anatomically connected – they are “ductless glands” meaning they distribute via the blood
Endocrine cells are going to be in areas of rich vascular beds – surrounding vasculature
Three types of hormones
- Peptides
- Amino acids
- Steroids
Which hormones are water soluble/insoluble
Peptides = water soluble Steroids = water insoluble
What are target organs?
- Tissues which express a specific receptor
- Cell surface receptors or intracellular receptors are present in target organs
- As long as there is a receptor expressed in a certain tissue, the hormone can elicit an effect there
How do hormones elicit an effect throughout the body?
By entering the blood and having a “sweeping effect” on all the tissues in the body that have receptors
- Hormones typically have a vast response – body-wide effects (heart, kidney, etc.)
- When you think about a hormone, need to think about all the different sites of the body it acts on
- Most of the effects you will need to know for this course are considered to be large sweeping endocrine effects
What is the hormone half life?
Duration of a hormone in circulation
- This is dependent upon protein binding
Describe the relationship between protein and hormone metabolism/activity
The greater the protein binding of a hormone, the longer the half life
This is because when a hormone is bound to a protein, it is protected from metabolism and excretion
This means that it is active longer, hence the longer half life
How is the volume of distribution affected by protein binding?
Volume of distribution will be lower when protein binding increases - the protein will be less widely distributed, more protected
How can you easily determine hormone levels?
- Most hormones will have a high rate of excretion in the urine, making it a good way to test hormones
- Compare normal hormone levels that should be excreted in the urine to the patient’s levels
- This is reflective of the amount of hormone levels in the blood
Describe peptide hormones
- 3-200 amino acids in size
- Synthesized as a pre-prohormone *
- Undergo post-translational processing such as peptide cleavage and glycosylation
- Stored in vesicles
- Released by a calcium-dependent process
- HYDROPHILIC (water lover) *** (can’t cross lipid membranes, so it will need to bind to a protein receptor and be transported across the membrane)
- They are, however, able to circulate in the blood freely
- Able to bind to cell surface receptors easily
Give some examples of peptide hormones
- Insulin
- Glucagon
- TSH thyroid hormone
Describe steroid hormones
- Derived from cholesterol
- Lipophilic (and hydrophobic)
- They circulate through the blood in the “bound” form
- Able to easily cross plasma membranes, meaning they will classically act intracellularly (although extracellular surface receptor activation is possible)
What are some examples of steroid hormones?
- Estradiol
- Progesterone
- Testosterone
- Cortisol
- Aldosterone
What are amino acid-derived hormones derived from?
Tyrosine
What are the two categories of amino acid-derived hormones?
Catecholamines and thyroid hormones (T3, T4)
What are catecholamines?
- Dopamine
- Norepinephrine
- Epinephrine
Epinephrine is the end product that the adrenal gland secretes (AKA adrenalin)
What do catecholamines and thyroid hormones have in common?
Hydrophilic (water lover)
What is unique about catecholamines and thyroid hormones?
Catecholamines
- Circulate freely in the blood
- Bind to cell surface receptors
Thyroid hormones
- Circulate bound to proteins in the blood
- Bind to intracellular receptors
What kind of receptors are the receptors for amino-acid derived hormones (catecholamines) and peptide hormones (TSH, LH, ADH)?
G-protein coupled receptors
What kind of receptors are the receptors for peptide hormones (i.e. insulin, growth hormone)?
Receptor protein tyrosine kinases (RTKs)
What kind of receptors are the receptors for thyroid hormones and steroid hormones?
Intracellular receptors
Summary of receptors
G-protein receptors
- Catecholamines (AA)
- TSH, LH, ADH (peptides)
Tyrosine kinase receptors (RTKs)
- Insulin, growth hormone (peptides)
Intracellular receptors
- Steroid hormones
- Thyroid hormones (AA)
So, all steroid hormones have intracellular receptors, amino acid hormones can either have G-protein receptors or intracellular receptors and peptide hormones can either have G-protein receptors or tyrosine kinase receptors.
How are hormones released?
- The release of hormones is pulsatile and periodic
- The release is regulated by multiple mechanisms
What is pulsatile and periodic hormone release?
Pulsatile
- Tiny, consistent spurts of hormones are released in a pulsing fashion
Periodic
- If you zoom out from that, you will see periodic patterns, such as LH peaking around day 14 of the menstrual cycle
What are the mechanisms that regulate hormone release?
- Neural (peripheral or central)
- Hormonal (feedback/feedforward)
- Nutrient or ion regulation
What are some examples of neural hormone release involving the peripheral nervous system?
Autonomic nervous system
- Parasympathetics
- Sympathetics
Somatic nervous system
What is an example of neural hormone release involving the central nervous system?
In the brain (hypothalamus, pituitary), prolactin hormone is synthesized and acts directly on the breast tissue to induce milk production
What are some examples of hormonal regulation of hormone release?
- Tropic hormones (TSH, LH) - means that they are hormones that act on endocrine glands as their target, they come from the anterior pituitary mostly
- Negative feedback
- Positive feedback (feed-forward)
What are some examples of nutrient or ion regulation of hormone release?
- When Ca++ is high, it signals back to the parathyroid gland to decrease the release of parathyroid hormone, which in turn prevents bone from releasing more Ca++
- When glucose is high, insulin is released from the pancreas, which signals the tissues to absorb the glucose for storage
What is important to realize about the three methods of hormone release?
They are integrated and can all be at play at once
What are the three types of hormone release feedback loops?
- Long loop
- Short loop
- Ultra-short loop
Describe a long hormone release feedback loop
The peripheral target organ secretes a hormone, which gets back to the hypothalamus and shuts it down
When a target organ sends a signal to the anterior pituitary or the hypothalamus
Describe a short hormone release feedback loop
When the anterior pituitary secretes a hormone which gets to the hypothalamus and shuts it down
When the anterior pituitary sends a signal to the hypothalamus
Describe a ultra-short hormone release feedback loop
You secrete something then right away you shut it down
When the hypothalamus sends a signal to itself
Describe three ways in which endocrine dysfunction can occur
1 - Dysfunction in the endocrine system due to either too much or too little hormone action
2 - Decreased responsiveness
3 - Decreased sensitivity
Describe dysfunction in the endocrine system due to either too much or too little hormone action
a. Abnormal hormone production
b. Change in receptor numbers
c. Change in receptor/enzyme/signaling molecule function
Describe decreased responsiveness
a. Decreased receptor number
b. Decreased enzyme/down stream target of receptor
c. Presence of non-competitive inhibitor
d. Decreased target cells
Describe decreased sensitivity
a. Decreased receptor affinity
b. Increased hormone degradation
c. Increased competitive inhibitor
On the hormone affinity curve, how would you represent decreased hormone responsiveness
A change in the maximal response that is possible
Max will shift down
On the hormone affinity curve, how would you represent a decreased hormone sensitivity?
A higher hormone response is needed to elicit the half-maximum response
Still able to reach the max
What are two different hormones you can test when there is a problem?
- Level of pituitary hormone
- Level of target hormone
What is going on if the pituitary hormone level is high, but the target tissue hormone level is low?
There has been a failure of the target organ
The hormone is being properly produced by the pituitary, but the target organ has failed to receive the hormone
What is going on if the pituitary hormone level is low and the target hormone level is low?
Pituitary gland failure
The pituitary is not making enough hormone
What is going on if the pituitary hormone level is high and the target hormone level is high?
Autonomous secretion of pituitary hormone OR resistance of target hormone action
The pituitary gland could be secreting too much or the target gland could be resistant to accepting the hormone and signaling target hormone release
What is going on if the pituitary hormone level is low and the target hormone level is high?
There is autonomous secretion of the hormone by the target endocrine organ
The target gland is producing hormone without the proper signal
What two things should you test together when there is a problem with the endocrine system?
- Hormone
- Regulator of the hormone
Examples
- Glucose and insulin
- Calcium and PTH
What two things should you test together when there is a problem with tropic hormones?
Tropic hormones = hormones that are released from the anterior pituitary and act on a different endocrine gland to release a different hormone
- Pituitary hormone
- Tropic hormone
What is happening when there is resistance of both a hormone and regulator?
Tissue resistance to the hormone
Example: glucose and insulin
When both glucose and insulin are elevated, it means the tissues are resistant to insulin
How long should you monitor someone when evaluating endocrine function?
- Monitor hormone excretion over 24 hours, better than 1 time plasma reading
- Most effective to be monitoring things over a 24 hour period because hormones are released in a pulsatile fashion
- Need to know that pattern, not just the levels in one moment in time
What are three ways in which you can use exogenous hormone agonists and antagonists?
1 - Physiological “add-back”
2 - Diagnostic indicator
3 - Pharmacological manipulation
Describe physiological “add back”
When someone has hypogonadism, you treat them with exogenous hormone (testosterone)
Describe diagnostic testing
- Stimulation test: give oral glucose, test the rise in insulin in the blood
- Suppression test: give dexamethasone to test negative feedback on ACTH release from pituitary
Describe pharmacological manipulation
- Birth control
- Management of type 1 and 2 diabetes
