1) Introduction to Endocrinology Flashcards
What is the classical definition of a hormone?
Chemical messenger released by one type of cell and carried in the bloodstream to act on specific target cells
What does the modern definition of a hormone include?
Factors produced and used locally without entering the bloodstream
What is endocrinology about?
Communication between cells in multicellular organisms
What is communication between cells required for?
- Development
- Homeostasis
- Reproduction
How is the stability of a multicellular organism achieved?
By a complex communication network (gene interaction)
How many cells is composed within each adult?
10^14 cells
How many protein-encoding genes do we possess?
21 000
What are the three layers of signalling networks?
- Within cells
- Between groups of cells (tissues)
- Between tissues
How do networks contribute to homeostasis?
Networks buffer against change
Why may dramatic changes, such as knocking-out a gene, not influence the output of the network?
- Because we have mechanisms that allow us to bypass this change by tuning our networks
- We have plasticity within our system
How many types of cells do we have?
200 to 250 types of cells
What accounts for the relative recent evolution of multicellular organisms?
The complexity of communication networks
When did life evolve? When did multicellular organisms evolve?
- Life: 3.8 billion years ago
- Multicellular organisms: 600 million years ago
Where are signals generated?
Special hormone-producing cells
What are recipient cells?
Cells that recognize signals and respond to them
How do various signals affect the response of a recipient cell?
The various signals are exposed at the same time, and are integrated by the recipient cell, which modulates the response
What is the function of the nervous system?
- Direct connection between concerned organs
- Rapid signals through nervous transmission
What is the function of the endocrine system?
- Sending chemical messages (hormones) into circulation
- Slow signalling response
What are the main control systems of the body? What are they responsible for?
- Nervous and endocrine system
- Responsible for monitoring internal and external environments and making adaptive changes (homeostasis)
What do endocrine cells secrete? What do they act on?
- Secrete hormones into blood vessels
- Target cells may be distant
What do paracrine cells secrete? What do they act on?
- Secrete hormones
- Act locally on neighboring cells
What do autocrine cells secrete? What do they act on?
- Secrete hormones
- Act on themselves or on identical neighboring cells
What do neuroendocrine cells secrete? Where is it secreted from?
- Secrete molecules
- From the axon terminals into the bloodstream
What do neurotransmitter cells secrete? What do they act on?
- Secrete neurocrine molecules
- From axon terminals to activate adjacent neurons
What do neurocrine cells secrete? What do they act upon?
- Secrete molecules
- From axon terminals to stimulate another neuron
What are the two general characteristics of hormones?
- Very low in concentration
- Very specific receptor
What units of concentration are generally used to measure hormone concentration?
ng/mL or pg/mL
What occurs if hormones levels are too high?
- The hormones activate other receptor types within that cell (inappropriate response)
- Ex: steroids for muscle building increase mammary tissue as well
What is the response cascade of a cell to a signal?
- Extracellular signal molecule binds to receptor protein
- Intracellular signalling protein cascade
- Signalling cascade acts on target proteins
- Cellular response
Which proteins may be targeted in response to a signal? What may that alter?
- Metabolic enzyme (altered metabolism)
- Gene regulatory protein (altered gene expression)
- Cytoskeletal protein (altered cell shape or movement)
What does the fate of a cell depend on?
- A multitude of extracellular signals
- Hormones never act in isolation
- The cell is always bouncing around a set-point to regulate a specific function within a normal range for the cell
What occurs to most cells if signals are absent?
Programmed cell death (apoptosis)
How may cells that synthesize hormones be organized within the body? (2)
- Clustered in endocrine glands (ex: thyroid gland)
- Interspersed as single cells in organs (ex: C-cells in the thyroid gland)
What are the three chemical types of hormones? What are the subtypes?
- Lipids (steroids and eicosanoids)
- Proteins (short polypeptides and large proteins)
- Amino acid derivatives
Steroids are a derivative of what compound?
Cholesterol
Where are steroid hormones found? Give examples.
- Gonads (estrogen, progesterone, testosterone)
- Adrenal cortex (cortisol, aldosterone)
Which steroid hormones are chemically very similar? How do they differ?
- Testosterone and estrogen
- Their 3D structure is different, allowing for receptors to differentiate them
How is testosterone converted to estrogen?
Aromatase
What do mineralocorticoids affect?
Mineral homeostasis
What do glucocorticoids affect?
- Glucose metabolism
- Immune function
What are eicosanoids?
Metabolites of arachidonic acid (20-carbon fatty acid)
What functions are prostaglandins involved in?
- Inflammation
- Reproduction
Give three examples of prostaglandins.
- Thromboxanes
- Leukotrienes
- Prostacyclins
________ and related compounds are collectively known as eicosanoids.
Prostaglandins
What is arachidonic acid?
20-carbon polyunsaturated fatty acid
What are the two major pathways of eicosanoid metabolism?
- Linear pathway
- Cyclic pathway
What does the linear pathway of eicosanoid metabolism produce? What enzyme is required?
- Leukotrienes are produced from arachidonic acid
- Requires lipoxygenase
What does the circular pathway of eicosanoid metabolism produce? What enzyme is required?
- Prostaglandin H2 is produced from arachidonic acid
- Prostaglandins H2 synthase (PGH2 synthase)
What catalyzes the committed step in the cyclic pathway of eicosanoid metabolism?
PGH2 synthase
What does prostaglandin H2 lead to? What enzymes are required?
- Prostacyclins (prostacyclin synthase)
- Thromboxanes (thromboxane synthase)
How does eicosanoid metabolism differ between different cell types?
Different cell types convert PGH2 to different compounds
Do eicosanoids have a short or long half-life? How do they mainly function?
- Short half-life
- They are rapidly degraded, so they are not transported to distant sites within the body
Give examples of short-chain protein hormones.
- GnRH
- Oxytocin
- Thyroid-releasing hormone (TRH)
Which two protein hormones are extremely similar in terms of their amino acid sequence, but possess profoundly different physiological effects?
- Arginine vasopressin (vasoconstriction and water retention)
- Oxytocin (milk ejection and labour)
How are subunits of large polypeptide protein hormones linked?
Disulfide bridge(s)
Give examples of large polypeptide protein hormones.
- Insulin
- Growth hormone
What are the hormones that are derived from tyrosine? What endocrine organ are they derived from?
- Thyroid: thyroid hormones
- Adrenal medulla: epinephrine, norepinephrine, dopamine
Which hormones are often used as neurotransmitters in the CNS? What type of hormone are they?
- Epinephrine, norepinephrine, dopamine
- Amino acid metabolites of tyrosine
What are the three characteristics of endocrine glands?
- Parenchyma (mass of secretory cells)
- Blood vessels (highly vascularized)
- No ducts
What are examples of permanent and transient endocrine structures?
- Permanent: pituitary, adrenal, pancreas
- Transient: ovarian follicle, corpus luteum
How many hormones may a specialized secretory cell produce?
- Usually, one type of cell produces one hormone
- A gland may be separated into lobes of cells; each lobe secreting a different hormone
Which endocrine glands possess neurons that may be specifically used to produce hormones?
- Hypothalamus
- Posterior pituitary
- Adrenal medulla
Where does posttranslational modification occur in the cell?
In the cytosol following translation of mRNA into protein
What are examples of posttranslational modifications?
- Disulfide bond formation from two separate sequences (GH, PTH), or a single sequence (insulin)
- Processing of polyproteins into smaller subunits (glucagon and calcitonin precursors)
- Assemble multiple subunits together and glycosylate (hCG)
What does the lipophilic leader sequence (signal peptide) enable the nascent peptide to do? What occurs afterwards?
- To cross the endoplasmic reticulum into the cisternal space
- The leader sequence is cleaved by a peptidase
What posttranslational modifications occur in the Golgi?
- Glycosylation
- Proteolytic cleavage
- Packaging into vesicles
Where are peptide hormones stored?
In secretory vesicles (granules) in the cytoplasm
What allows for the movement of secretory vesicles containing peptide hormones to the cell membrane?
Microtubules (cytoskeleton) and microfilaments
What is required for the activation and release of a stored peptide hormone? What may the stimulus be? What does it normally involve?
- A stimulus is required (stimulus-secretion coupling)
- May be hormonal
- Usually involves changes in calcium permeability of the cell membrane (opening of Ca2+ channels)
What is the benefit of peptide hormones?
They may be pre-synthesized and stored in the cytoplasm as granules
Where are steroid hormones stored?
They are NOT stored, but must be synthesized de novo since they are lipophilic
What is the downside of steroid hormones?
They must be synthesized de novo, which requires more time for release
In which organelle does the cleavage of the side chain of cholesterol occur? What does cholesterol become?
- Mitochondria
- Becomes pregnenolone, which becomes progesterone
Where are enzymes for steroid hormone synthesis located within the cell?
Mitochondria and smooth ER
How does steroid hormone synthesis occur?
- Cholesterol from cytosolic stores move into the mitochondria for conversion to pregnenolone
- Transport into the smooth ER
- Transformation into the appropriate hormone
- Diffusion from the cell
How do hydrophilic hormones circulate in blood?
In a free state
How do hydrophobic hormones circulate in blood?
Require carrier proteins that are specific for the particular hormone
What is the major function of binding proteins to hydrophobic hormones?
Binding proteins act as a buffer to protect the hormone from degradation in the liver
What do binding proteins binding to hydrophobic hormones inhibit?
Only the free hormone is biologically active, so it must dissociate from the binding protein to bind to the receptor
How does the half-life of peptide hormones differ from large protein hormones?
- Peptide hormones have a very short half-life, as they are degraded by proteolytic enzymes
- Large protein hormones are glycosylated, which extends their half-life
What are the three levels of control of synthesis and secretion of hormones?
- Neural input (brain, hypothalamus)
- Hormonal stimulation/inhibition (inhibitory factors, feedback system)
- Metabolic status (stress, blood concentrations of substances)
What is the effect of a lack of GH in children? What about in adults?
- Children: dwarfism
- Adults: atrophy of muscle tissue
What is the effect of a lack of cortisol and aldosterone from the adrenal gland?
- Addison disease
- Increases ACTH secretion by the pituitary
- Melanocyte-stimulating hormone secretion is also increased, which leads to excessive freckling
What is the most common endocrine disorder? What are the two possible causes?
- Diabetes mellitus
- Lack of secretion of insulin from B-cells of the pancreas
- Insulin receptor defect
What are endogenous mechanisms?
Signals from the brain that are independent of external cues
Give an example of a mechanism entrained by external cues?
Light-dark cycle
What is the circadian rhythm? What is the infradian rhythm?
- Circadian: 24h cycle
- Infradian: 28-day menstrual cycle
When is cortisol secretion maximal?
Between 4 and 8 AM
When is GH and PRL secretion maximal?
1 hour after going to sleep
When may rhythms change?
During development
How does gonadotrophin change during development (puberty and adulthood)?
- Puberty: released mainly at night
- Adulthood: released in a pulsatile fashion
What must be taken into account when measuring hormone levels?
Endocrine rhythms
What are common techniques used in endocrinology?
- Ablation and replacement
- Bioassays
- Immunoassays
- Immunocytochemistry
- Blot tests
- Pharmacological techniques
- Genetic techniques
What are induced ovulators? What animal is an induced ovulator?
- Females must mate in order to ovulate
- Rabbits
What was the rabbit test?
- If fertilization occurs, hCG is produced by the placenta 8 days afterwards
- Urine from a pregnant woman is taken and injected into a rabbit, stimulating the ovary to cause ovulation
- The rabbit is killed, and the ovaries are examined to determined if the woman is pregnant or not (+ corpus luteum)
