Introduction Flashcards
Classical definition of ‘hormone’
How is this different from the modern definition?
chemical messenger released by 1 type of cell -> carried in bloodstream to act on specific target cells
Modern definition also includes factors made/used locally (without entering bloodstream)
Why is an endocrine system essential in multicellular organisms?
allows for communication between cells
What are 3 basic functions in the body that require the endocrine system?
- differentiation (development from egg to adult)
- homeostasis (maintain environment for cells to live)
- reproduction
The human body is composed of (number)____ cells, coordinated by the networking of ____ ____ ____.
10^14
protein encoding genes
the 3 layers of signaling networks:
- within cells
- between groups of cells (tissues)
- between tissues
What is the advantage of having a complex control network in genes/body systems?
acts as BUFFER against mutation; even if one gene pathway knocked out, can still reach ‘output’ through other pathway
Earliest sign of complex animal life:
550-590 million yrs ago (pre-cambrian period)
True/False: all hormones are extremely specific for 1 type of target cell
False; some can target multiple cell types, but response can vary depending on cell type
hormones are generated by ______, and recognized by: ______, which contributes to an ______ response.
hormone-producing cells
target/recipient cells
integrated response
What is the meaning of ‘integrated response?’
cells exposed to many signals -> summation of signals (positive/negative) => total response to ALL signals combined
What are the 2 main control systems of the body? Compare them.
nervous system (DIRECT connection, fast, immediate response/changes)
endocrine system (chemical message to remote areas, slower, ADAPTIVE changes)
What are the types of signalling molecules? What is their role? (5)
Endocrine: go into blood vessels -> distant cells
Paracrine: act on nearby cells
Autocrine: act on self/identical neighbors
Neuroendocrine: from axon terminal -> bloodstream
Neurotransmitter: from axon terminal -> adjacent neuron
True/False: the amount of hormone used as a signal in blood is usually in mg/mL
False: VERY low, usually ng/ml or pg/ml
True/False: hormones are HIGHLY SPECIFIC
True: one hormone -> one receptor
What are some examples of molecule types that can act as hormones?
peptides (3 - >180aa) modified AA cholesterol-based (steroids) synth from FA gases
Example of a gas hormone:
Nitric oxide
Example of hormone type synthesized from fatty acids:
prostaglandins
how does a hormone signal trigger an effect? describe the general steps that occur
bind to receptor protein conformation change activate signal cascade activate target genes/proteins trigger cellular response
examples of potential cell responses:
altered metabolism (alter enzyme action)
altered gene expression (alter gene regulatory protein)
alter cell shape/movement (alter cytoskeletal protein)
what happens in a cell with NO SIGNALING?
programmed death
Where are hormone-synthesizing cells found? (2)
In clusters (Major endocrine glands)
interspersed in organs as single cells
The 3 chemical classes of hormones:
- lipids (steroids, eicosanoids)
- proteins (short polypeptides, large proteins)
- AA derivatives
Steroid hormones are derivatives of ____. What are their chemical properties?
cholesterol
large molecules with hydrocarbon ring, HYDROPHOBIC
Where does cholesterol come from, and where is it found in the body?
de novo (synth) or from diet in cell membranes or lipoproteins
Cholesterol can be processed into what products? (3)
vitamin D
bile acid (digestion)
steroid hormones
What are 2 types of hormones that are steroid hormones
sex hormones
adrenal steroids
all cholesterol derivatives can be recognized by the ___ ____
sterol ring
How is testosterone coverted to estradiol?
AROMATASE enzyme
Why can hormones with very similar chemical compositions have very different effects?
slight changes in chemical structure can cause large structural changes -> affect receptor fit and action
What steroids are produced in the adrenals? What is their function?
mineralocorticoids (mineral homeostasis)
glucocorticoids (glucose metabolism, immune function)
What steroids are produced in the gonads?
estrogens
progestins/progestagens
androgens
What are eicosanoids? what does it include?
Lipid hormones derived from 20C fatty acid (arachidonic acid)
Includes: prostaglandins, thromboxanes, leukotrienes, prostacyclins
True/False: Arachidonic acid is an EFA in the diet
False, can produce from phospholipids or diacylglycerol
What are the roles of prostaglandins? (2)
inflammatory reaction
reproduction
How are prostaglandins (PGH2) produced from Arachidonic acid?
cyclooxygenase enzyme (COX) /PGH2 synthase (cyclic pathway)
How are Prostaglandins related to thromboxanes and prostacyclins?
common precursor (PGH2)
How are leukotrienes produced?
arachidonic acid -> lipoxygenase enzyme (linear pathway)
What type of signal (according to function) would eicosanoids be classified as?
paracrine (act locally)
True/False: eicosanoids can have far-reaching effects on the body due to efficient transportation through the blood
False: only act on cells close to their formation site
rapidly degraded
What determines what type of eicosanoid PGH2 will be converted to?
Cell type (diff cells will convert it to diff things)
_____hormones are short-chain peptide protein hormones. Give 4 examples:
Neurohormones GnRH Oxytocin TRH ADH
True/False: mutations in AA sequence in peptide protein hormones can have major effects
True: short sequences, so can cause dramatic changes
What are characteristics of large protein hormones?
linear chain
subunits linked by S-S bonds
specific 3D structure (for linking with receptor)
examples of large protein hormones:
insulin
GH
What 2 types of hormones are AA metabolite hormones? What are they made from?
Thyroid hormones
Adrenal medulla hormones
made from Tyrosine
What are the thyroid hormones?
thyroxine (T4)
Triiodothyronine (T3)
What are the adrenal medulla hormones?
What is their alternative function?
epinephrine
norepinephrine
dopamine
also used as neurotransmitters
General composition of endocrine glands:
parenchyma (cell mass) - made of secretory cells
blood vessels - highly vascularized
no ducts
Are all endocrine glands permanent?
many are (pituitary, adrenal, pancreas, etc)
but some are transient (ovarian follicle, corpus luteum)
What types of cells can make hormones?
specialized secretory cells (1 cell -> 1 hormone)
neurons
where can hormone-producing neurons be found in the body?
hypothalamus
posterior pituitary
adrenal medulla
process of hormone synthesis for protein hormones:
- transcription
- translation
- phys/chem modification (cleave chain to make peptides; interact/link subunits; form 3D structure)
An inactive molecule that must be modified to become an active hormone is known as a _______
preprohormone
What is a ‘signal peptide’ and what is its role in hormone synthesis?
signal peptide = lipophilic leader sequence -> allow peptide to cross ER into cisternal space before cleaved off (further modified & packaged for export)
What are some examples of peptide phys/chem modifications?
S-S bridges, glycosylation, cleavage
peptide prehormones are sometimes packaged into vesicles along with a ______
activating peptidase
Can peptide hormones be stored?
Yes; stored in GRANULES (secretory vessels) in cytoplasm
How are stored peptide hormones secreted?
stimulate -> change Ca permeability (open Ca channels)
granule brought to surface by cytoskeleton microtubule/microfilament ->
How are steroid hormones synthesized?
cholesterol taken from lipid droplets in cytosol
side chain cleaved by mitochondria (become prenenolone)
modified in ER
Can steroids be stored?
no (immediate egression from cell)
How are peptide/protein hormones transported in blood?
can circulate in free state
How are hydrophobic hormones transported in blood?
requires specific carrier protein (usually binding proteins or globulins)
What is the significance of a hormone binding protein?
protects from degradation in liver (act as buffer)
solubilize in blood
remains inactive while bound
What is the difference in half-life of small peptide vs large protein vs hydrophobic hormones?
small peptide; very short half-life (quick degraded by enzymes)
proteins: longer half life
hydrophobic: longest half life (protected by carrier)
What are the 3 main controls for synthesis and secretion of hormones?
- neural input (brain, hypothalamus)
- hormone stimulation/inhibition (releasing/inhibitory factors; feedback)
- metabolic status (stress, blood concentrations)
What are positive and negative feedback?
positive: resulting hormone production -> feedback and promote MORE hormone production
negative: resulting hormone production -> feedback to STOP hormone production
Lack of GH will lead to:
Dwarfism (children) muscle atrophy (adult)
Adrenal gland deficiency results in lack of ___ and ____, known as ____ disease.
cortisol, aldosterone
Addison’s disease
What causes the freckling seen in Addison’s disease?
no cortisol/aldosterone -> no neg feedback to shut off ACTH -> pituitary keep making ACTH, co-secreted with MSH (melanocyte stimulating hormones) -> freckling
Besides the problems due to lack of hormone, what other problems arise from defective enzymes in steroid synthesis?
accumulation of intermediates
What is the most common endocrine disorder? What causes it? (2)
Diabetes mellitus
lack of insulin secretion from beta cells (from cells of Langerhans in pancreas); or from receptor defect (unresponsive)
What determines ‘endocrine rhythms?’
endogenous mechanisms: from brain
entrained by external cues
What are positive and negative feedback?
positive: resulting hormone production -> feedback and promote MORE hormone production
negative: resulting hormone production -> feedback to STOP hormone production
Lack of GH will lead to:
Dwarfism (children) muscle atrophy (adult)
Adrenal gland deficiency results in lack of ___ and ____, known as ____ disease.
cortisol, aldosterone
Addison’s disease
What causes the freckling seen in Addison’s disease?
no cortisol/aldosterone -> no neg feedback to shut off ACTH -> pituitary keep making ACTH, co-secreted with MSH (melanocyte stimulating hormones) -> freckling
Besides the problems due to lack of hormone, what other problems arise from defective enzymes in steroid synthesis?
accumulation of intermediates
common techniques in endrocrinology: (9)
ablation & replacement bioassays immunoassays immunocytochemistry (ICC) autoradiography blot tests in situ hybridization pharmacological techniques genetic techniques
What determines ‘endocrine rhythms?’
endogenous mechanisms: from brain
entrained by external cues
the 24hr cycle of the body is known as: _____ ____
circadian rhythm
What is RIA?
radioimmunoassay
use known amount of antibody & radiolabelled hormone
add increasing amounts of unlabelled hormone -> displaces labelled (comp. binding) -> construct standard curve
use curve to estimate hormone amount in test sample
What is infradian rhythm?
28 day cycle (menstrual cycle)
How do gonadotropin levels differ in adolescents and adults?
Puberty: released mainly at night
Adult: pulsatile rhythm
Why is it important to consider hormone fluctuation rhythms?
need to take into account when measuring levels (‘normal’ level is different according to time in cycle or life stage)
common techniques in endrocrinology: (9)
ablation & replacement bioassays immunoassays immunocytochemistry (ICC) autoradiography blot tests in situ hybridization pharmacological techniques genetic techniques
Why are imaging studies useful in endocrinology?
MRI and CT can allow detection of tumours, visualization of glands
how does the ‘rabbit test’ work?
hCG is made by placenta 8 days after fertilization
inject urine into rabbit (induced ovulator) -> hCG will trigger ovulation, form corpora lutea
Kill rabbit, look in ovaries for corpora lutea
What is RIA?
radioimmunoassay
use known amount of antibody & radiolabelled hormone
add increasing amounts of unlabelled hormone -> displaces labelled (comp. binding) -> construct standard curve
use curve to estimate hormone amount in test sample
What is EIA? How is it similar/different from RIA?
enzymoimmunoassay
also competitive binding assay (antibodies) but no radioactive tags; use color-change to indicate
ex: home preg test
Where can samples be obtained from, for RIA or EIA tests?
blood or urine (depends on hormone)
What is indirect measurement for hormone levels?
measure another compound that indicates level of hormone (ex: measure glucose instead of insulin)
What are provocative/suppression tests? What is the advantage?
assess status by maximally stimulate/suppress hormone release, compare to healthy individuals
useful for hormones with natural fluctuation, less samples needed
Why are imaging studies useful in endocrinology?
MRI and CT can allow detection of tumours, visualization of glands
____ gene editing can help correct inborn endocrine diseases by _______
CRISPR/Cas9
collecting cells -> modifying in vitro to correct -> re-introducing in patient
What are ‘mimetic designer cells?’ What is an example of how it is used to treat an endrocrine disease?
modifying cell pathways
treating diabetes: made synthetic circuit (coupled glycolysis-mediated Ca entry to gene for insulin production); made new glucose-sensitive pathway for insulin production
