Physiology (Endocrine) Flashcards
Pre Hormones vs. Hormones
Pre-hormones - not water soluble = need a carrier protein
Hormones = free hormone that is active ad availible for target tissue
Release of the carrier protein = based on equilibrium between the pre-hormone and hormone
Endocrine
Secretions that stay in the body (secreted into the blood)
- Endocirnology = Study of signlaing (Signal goes to blood –> goes to target tissue -> signal causes effect)
- Endocrine = humeral
Function - Endocrine glands use hormones to regulate bodily function
Exocrine
Secretions go outside the body or to lumen (Ex. sweat going t sweat galnds or bile or pancreatic enzymes)
Basic science/Clincal of Endocrine
Endocrinology is clinically and basic science orientated
Basic science of endocriniology (overall)
Includes principals of homrone synthesis + secretiono/action + feedback regulation/homeostais + receptor binding/intracellular signaling –> ALL fundemental concpets that are critical to the fundation to understadning many specialties and scinetific disaplines
Clincal of Endocrinology
Clincal endocrinology = specialty of internal medicine concerned with dieases that affect the “classical” endocerine organs
- Also looks at hormone regulation and feedback
Can also encompess obesity + osteopereosis + lipid disorders + hypertension
- Can include bone dieases + lipid disorders
Can overlap with other speciaties (ex. Oestoperosis and rickets = Endocronology + renal OR can iber lap with gynology/urogology (reproductive endocrinology)
Classical endocrine organs
- Thyroid
- Parathyroid
- Pituitary
- Adrenals
- Pancreatic islets
- Gonas (overy and testes)
Endocrinology Basic Science
Basic science of endocronology begins with the study of hormones and their actions on organ tissues
Looks at:
1. Receptors + intracelular signlaing + trasncriptional regulation
2. Intracellular communication within tissues and between organs
Discovery of new hormones and emergnce of diseases means the feild is always evoloving
- Example - Leptin is new
- Example 2 - Finding new actions of hormones
Endocrone vs. nervous system
BOTH - major communication systems in body
Endocrone - Release of homrone to the blood
- Affects distant tissue + indirect affect (lack direct contact)
- Secretion of hormones that go through the blood is more gradual
- Can have a sort effect (rapid acting with rapid effect) or long effect
Nerve
- Loclized effect +
- Direct communication between nuerons and each other or neurons and target tissue by innervation
- Fast - because electrical signals
Hormone
Chemical signal secreted into the blood stream to act on distant tissues to regulate somthing in the target cell
Types of hormones
- Act on nuclear receptors
- Act on surface receptors
Different based on where action occurs in cells
Nucelar receptor hormones
Nuclear = class of classical receptors
Includes:
1. Thyroid hormone (derived from tyrosine)
2. Steroid hormone (derived from choletral)
- With intact steroid nuceus (Ex. Gonadal ad Adrenal steroids)
- With borken steroid nucleus (Vitamen D)
BOTH = cross the lipid barrier –> bind to intracellular recepter
Surface Receotor horomone
Includes:
1. Polypetides
- Some are small (Ex. TRH is 3 Amino Acids)
- Some are big (Ex. GH is 200 AA)
- Some are Glycosytlated (Ex. TSH + FSH + LH + hCG)
2. Monoamines and derivatives (Ex. Seratonin + dopamine + norepinephrine + epinerphines)
3. Prstogalndins
ALL - bind to the outside of cell (don’t pass the lipid membrane) ; all require signal transduction via second messengers intracelularly
Nucelar receptor hormone structures
Thyroid homrone - derived from Amino Acid
Steroid Homrone - derived from chlestral (have cholestral backbone + have substituents)
- Substituetnts define how it binds to intraceular recptor –> bind vcausing confirmational change –> causes effect
Nuclear receptor superfamily
- Sterroid homrone receptors (includes sex hormones)
- Heterodimeric recpetors - bind in heterodimer with another heterodimer receptor
- Orphan Receptors - don’ have known obvious ligand
IMAGE - has list of all of them
Homrones that act on the cell surface
Left side - peptide hormoe
Right - shows epinephrine + norepinephrine (Amine derived)
Mechanism of hormone (Nucelar receptors)
Have residue within cells
Receptors = bind with ligand to nucleas –> regulate trasncripton through hormone activation –> end have phenotypic change (hormone effect)
IMAGE - shows process
Mehcnaism of cell surface recptors
Growth factor receptor = reacts with tyrosine kinase
Signal using signla trasnduction mediater
Hormone = ligand for rceptor –> binds –> acts on target tissue that has the cell surface receptor
Types of cell surface receptors
Example:
1. Growth factor receptor
2. GPCR - svene mebrane spaning domain receptor (Ex. NE, TRH, LH)
Where do hormoes act
Can divide classical hormones based on distance:
1. Endocrine
2. Paracrine
3. Autocrine
Endocrine hormines (in terms of diatnce)
The hormone is secreted into the blood and transported to anotheer site (target) where it exerts function (stimulatory or inhibitory)
Classical hormones = often affect distant organs
Paracrine
The hormone acts locally on nearby cells
- Not traveling far in the blood
Example - sex steroids in the overy
Autocrine
The hormone acts locally on the cell that has produced it
Example - Insulin
- Pancreatic islets = have endocrine subtype (autocrine) – signal to each other in a autocrine/oaracine fasion (not going into blood stream)
Where do hormones come from
Overall - there are sevral endocrine glands
- Have secretion of hormone from glands that make specific hormones
Glands are:
1. Ductless (as oppose to exocrine which have ducts to get things to the GI tract)
2. Highly vasculrized
- Example - pancreatic islets see 20% of the blood volume at any gven point
- Needed to the hromones can ho into the blood and signla to the rest of the body
There are 6 clasical endocrine glands - descrete organs with hormone secreaton as their primary function
- Also have many “non-clasical” endocrine organs that have other primary functions
Hormone secreation
- Basal Secretion - always being secreted at low levels
- Stimulated secretion (tonic) - stimulated by different things to secrete hormone
Secrete hormon from pool of prescuror hrmone into the blood
- Secretion can be tonic or basal
Example - Insuline secretion is basal and glucose stimulated
Stimulated secretion
Have a chemical sensor that increases or decreases secretion
- BUT not electrical = not like nerves
Pulses of hormone secretion
Pulses may have different periodicity - Flucuation of homrone in the blood can be stocahctic (random) OR can be periodic
Example:
1. Circa-horal - every hour
2. Cia-dian - Every day (Ex. Ciacadian rhythm - Corisol + testostrone)
3. Ci-Trintan - Every month (Ex. menstral cycle)
Free Hormones
Active fraction of hormones for celular action and feed back
- Often Amine and Polypeptide hormones because they are water soluble (have a shorter hald life) (EXPPTION is insuline like growth factos bound to IGFBP)
In the lab you should measure free hormone but that is not always possible
- If you measure total hrmone and there is a carrier protein abnormality the total hormone may not refect the free hormone
Inactive hormones
Fraction of hormones that are biund to carrier protein largest fraction of hormone)
- Hormones that are protein bound are cleared more slol from circulation by the liver and kindeys (have a longer half life) (ex. thyroid + steroid)
Bound and free fractions of hormone are in equilibrium
Circulation of steroid and thyroid hormones
Steroid and thyroid homrones = circulate bound to carrier proteins because they are not water soluble
Example -
1. Thyroglobulin bins to T3 and T4
2. SHBG bines to testostrine and E2
3. CBG for cortisol
4. Non-specific Albumin and pre-albumin
EXCEPTION - mineracortoid steroids don’t have a carrier (Ex. aldostrone)
Homrone action
Hormone ats as ligand on hormone receptor
- Only a small fraction of circulating hromone is taken up by the target tissue
- Bulk of clearance is dne by the liver and kidneys
- Have many kinds of enzymatic reactons (Ex. Hydolysis + Oxidation + Hydroxylation) –> allows hormones to be cleated by the liver?
- Smal fraction is extreted intact in urine or feces
Have:
1. Agonist
2 Partial Agonist
3. Antagonist
***Can be based on binding seperatley
Hormone regulation
Most hormones have another hormone that regulates their secretion
- Interaction between hormones = Feedback
- Most organs secrete hormones AND wil scerete asecond ormoen or a byproduct that will regulate the first hormone
Two types:
1. Stimulatpry (Trophic) - Hormones that stimulates the secreation of another hormone
2. Inhibitory - Hormone tha inhibits the secretin of another hormone
Negative feedback
A trophic hormone inducdes the secretaion of a second hormone which in turn inhibits the secretionn of that FIRST hormone
- Taregt releases a hromone that tells intital cell to stop making the hormone
- Increase in Homrone A leads to increase in Hormone B which inhibits production
More common
Positive Feedback
Amplifies abundent signals
Target cell makes substance to tell the initial cell to make more hormone
- Increase in hormone further increases producton loop
Can lead to runaway affect
Overvoew of the 6 Classicla Endocrine organs
Pituity - Secretion hormone that regulates other endocrine glands + tissues
Functional Charcterization of Hormones
ALL regulates by multiple hromones from diffreent places
Functional Characterization of Endocrone diseases
- Hypofunction
- Hyperfunction
- Hormone release resistce syndromes