Endocrine system and principles of hormone measurements Flashcards
hormones
chemical messengers from a gland or pocket of cells within an organ that regulate the activity of certain cells or organs
neurotransmitters
synthesized in a pre-synaptic neuron and travel across a synapse to another neuron or to muscle
neuroendocrine hormones
hormones produced by neuronal cells that are secreted into the bloodstream to act on distant cells (ex. neurons in hypothalamus release hormones into portal circulation to reach the anterior pituitary)
most hormones are (small or polypeptides)
polypeptides
Two main types of hormones
Lipid soluble
Water-soluble
Steroid hormones
lipid soluble
Require carrier proteins to circulate in bloodstream
Diffuse directly into cells to bind CYTOSOLIC receptors
Thyroid hormones
derived from tyrosine and iodine
lipid soluble
require carrier proteins to circulate in the bloodstream
diffuse directly into cells and bind NUCLEAR receptors
Water soluble hormones
receptors on the cell surface Amines are mainly derived from tyrosine Peptides Proteins (usually pro-hormones ex. proinsulin) Glycoproteins
C-peptide
an inactive derivative of proinsulin that can be used to asses the reserve capacity of the pancreas
Albumin
a low affinity, high capacity hormone carrier
free hormone
capable of producing a hormonal effect
Simple control of the endocrine system
self limiting signal and effect
may have a threshold level to initiate response
negative feedback
signal induces response, response inhibits production of signal
very common
positive feedback
response amplifies original signal until system can no longer respond or signal is removed
inhibitory control
release of hormone controlled by inhibitor, remove inhibitor to allow release
ex. prolactin release by anterior pituitary is inhibited by dopamine
endocrine rhythms
pulsatility of hormones due to internal rhythms (ex. circadian)
Over secretion
due to loss of feedback control through end organ failure, or:
ectopic production by alternate site
Under-secretion
loss of stimulation
endocrine organ failure (ex. premature menopause as ovaries start to fail)
Disordered Metabolic Pathway
may occur from reduced end product or increased intermediates that may or may not have endocrine activity (ex. congenital adrenal hyperplasia)
Measurements of hormones: Bioassays
specific for biologically active hormones but are inaccurate, imprecise, inconvenient, time consuming, and expensive (ex. anti-TSH receptor)
Chemical methods
depend on specific chemical markers on hormones (ex. -OH group on a steroid)
nonspecific, insensitive, and imprecise
Chromatography
works well for small molecules (ex. neuroendocrine hormones, steroids)
prior to use of Tandem mass spectrometry
Immunoassays
measure concentration, not activity
usually use monoclonal antibodies, sometimes polyclonal
automated (high throughput), accurate, precise
method of choice for large protein hormone molecules
Basic components of immunoassays:
Analyte
Antibodies specific for the analyte
A label/ detection system
A method to separate bound from free components (ex. washing)
Competitive immunoassays
the analyte and a tracer (labeled hormone) compete fofr limited amount of antibody
used for smaller analytes which can only bind one antibody at a time
the amount of tracer at the end is inversely proportional to the amount of analyte in the sample
Noncompetitive (sandwich) immunoassays
all of the analyte binds a non-limiting concentration of antibody
no competition step
second antibody with tracer binds a distinct epitope on the analyte
used for larger analytes
the signal is directly proportional to the concentration of the analyte
Common radioisotope
125I
Fluorescent label
Eu (europium)
Chemiluminescent label
acridinium ester
Ruthenium particle:
chemiluminescence
Colourimetry
a coloured complex generated when enzymes are incubated with the correct substrate
Beads
gold, latex
