Hormones Flashcards
metabolism at the organism level
- role and structure of specific tissues and organs
- flux of metabolites from organ to organ
- hormonal regulation of metabolism
- control of body mass
neuronal vs hormonal signalling
In neuronal signaling, nerve cells release neurotransmitters that act on nearby cells. Distance may be small (<1 um).
In hormonal signaling, hormones are carried by the bloodstream to nearby cells or other organs. Distance may be great (1 m or more).
hormone-receptor interactions
- Highly specific and high-affinity
- Different types of cells have different sets of receptors.
- Different cells with the same receptor can have different downstream effects.
- Even structurally similar hormones can bind different receptors.
- Interactions are high-affinity so that only low amounts of hormone are needed.
5 types of downstream events following hormone binding
- A secondary messenger (cAMP; inositol triphosphate, IP3) is released inside the cell: allosterically regulates enzymes
- A receptor Tyr kinase is activated.
- A hormone-gated ion channel is opened or closed: resulting in changes in membrane potential
- A steroid bound to receptor protein in the nucleus alters gene expression: resulting in changes in membrane potential
- An adhesion receptor sends information to the cytoskeleton.
hormones: extracellular vs intracellular
act on: cell surface receptor (doesn't enter cell) or nuclear receptor (acts internally)
peptide and amine hormones bind extracellularly
- Insulin is a peptide hormone; epinephrine (adrenaline) is an amine hormone.
- They bind to receptors that span the membrane and induce conformational change that produces a second messenger.
- It results in signal amplification and many targets.
3 classes of mammalian hormones
Based on path from release to target
- Paracrine: released into extracellular space, diffuse to neighboring target
o example: eicosanoids
- Endocrine: released to blood, carried to target cells
o example: insulin, glucagon
- Autocrine: affect the cell where they’re produced (but bind to surface receptors)
additional classification based on hormones chemical structure
membrane receptor: peptide, catecholamine, eicosanoid
nuclear receptor: steroid, vitamin D, retinoid, thyroid
cytoplasmic receptor: nitric oxide
peptide hormone insulin
- Peptide hormones include insulin, glucagon, somatostatin
- Insulin is: synthesized on ribosome of B cells as preproinsulin and processed into the 5.8 kDa active form
o stored in secretory vesicles in B cells - conversion of pre-proinsulin to proinsulin and mature insulin (to the right)
role of insulin
- Secreted in response to increased blood glucose levels.
- Binds to receptors in muscle, the brain, the liver, adipose tissue, and other fuel-metabolizing tissues.
- In muscle, insulin facilitates glucose uptake.
- In the liver, insulin promotes glycogen synthesis.
- In adipocytes, insulin promotes glycerol synthesis and inhibits breakdown of fats.
conversion of glucose –> glycogen or TAGs
Insulin stimulates glucose uptake in muscle and fat.
o glucose –> G6p
o Glycolysis begins when G6p concentrations rise and produce acetyl-CoA.
Liver: insulin stimulates glycogen synthase and inactivates glycogen phosphorylase.
o G6P –> G1P –> UDP-glucose –> glycogen
- Also in the liver, insulin stimulates fatty acid synthesis from excess acetyl-CoA.
o acetyl-CoA –> TAG, exported by VLDL
Fat: insulin stimulates TAG assembly.
o Glucose 6-phosphate –> glycogen
some peptide pro-hormones can yield multiple products
- pro-opiomelanocortin (POMC)
- 8 different cleavage sites
- produces at least 10 different peptide hormones
(includes B-endorphin, melanocyte-stimulating hormones) - mutations in the POMC gene are associated with obesity
Catecholamine hormones: epinephrine and norepinephrine
- Synthesized in adrenal glands
- Synthesized from the amino acid l-tyrosine
- Concentrated in storage vesicles and released ( like peptide hormones)
- Bind to extracellular receptors to generate secondary messengers (like peptide hormones)
Eicosanoid hormones
- Includes prostaglandins, thromboxanes, and leukotrienes
- Are not synthesized in advance
- Produced when needed from arachidonic acid via phospholipase A2
- Paracrine hormones (act nearby)
- Play a role in inflammation, smooth muscle contraction, platelet function
Steroid hormones made from cholesterol
- Includes cortisol, testosterone, estradiol
- Bind to carrier proteins to travel through the bloodstream (endocrine)
- Enter cell nucleus; bind to nuclear receptor to alter gene expression
o Some may also bind to a plasma receptor.
Vitamin D hormones (nuclear receptor)
- Obtained from food or from photolysis of 7-dehydrocholesterol in sun-exposed skin.
- Calcitrol (1a,25-dihydroxycalcitrol) - active form
- Affects the transcription of genes that regulate [Ca2+] and the balance between Ca2+ deposition and removal from bone.
Retinoid hormones (nuclear receptor)
- Derived from Vitamin A1 (retinol), which is derived from B-carotene.
- All cells have at least one form of retinoid receptor.
- The hormone-receptor complex regulates genes governing cell growth and differentiation.
- Most active in cells experiencing rapid growth
o e.g. lung epithelia, skin, immune system, cornea
thyroid hormones (nuclear receptor)
- T3 (triiodothyronine) has three iodines at Tyr residues.
- T4 (thyroxine) has four iodines.
- Precursor thyroglobulin –> yields T4
- which is converted to T3.
- The receptor-hormone complex increases expression of enzymes that yield energy.
Nitric oxide interacts (intracellular receptor)
- Nitric Oxide (NO) is a free radical made from arginine and O2 by NO synthase.
- Acts near its point of release.
- It enters the target cell and activates guanylyl cyclase to increase cGMP.
o leads to activation of cGMP-dep protein kinase
o leads to relaxation of contractile proteins in smooth muscle of blood vessels –> lowers blood pressure
major endocrine glands
- Brain: hypothalmus, pituitary
- Thyroid, parathyroid
- Adipose (fat) tissue
- Adrenals (on top of the kidneys)
- Pancreas
- Ovaries/Testes
top down vs bottom up hormonal signalling
Top down
- Some signals originate in the brain, and the signal is sent out to the body.
- examples: oxytocin, vasopressin, cortisol
Bottom up
- Some signals originate from elsewhere in the body and send messages to the brain.
- examples: epinephrine (adrenaline), insulin, leptin
hypothalamus
- coordination centre of the endocrine system
- Hypothalamus - small region of the forebrain
- Receives and integrates nerve signals from the CNS
- Synthesizes small peptide hormones oxytocin and vasopressin.
- Also synthesizes several factors that regulate function of the anterior pituitary.
pituitary release of hormones target other glands
Posterior Pituitary (neurohypophysis) contains the end of axons from the hypothalmus. o produces short peptide hormones made in the hypothalmus (vasopressin, oxytocin)
Anterior Pituitary (adenohypophysis) = endocrine organ that receives releasing factors from the hypothalamus via blood vessels. o produces long peptide hormones called tropins o activates second targets: adrenal cortex, thyroid, ovaries/testes
posterior pituitary hormones: oxytocin and ADH
Oxytocin promotes:
o contraction of smooth muscle of the uterus during labor
o milk release from the mammary gland
ADH promotes:
o water reabsorption in kidneys to maintain salt balance
o constriction of blood vessels; increases blood pressure
Both hormones:
o play roles in social behavior such as pair bonding; these CNS effects do not involve pituitary secretion
hypothalamic cortisol cascade
- Fear, infection, hypoglycemia, and so on send electric signal to the hypothalmus.
- -> ~ng of corticotropin-releasing hormone
- -> anterior pituitary releases ug corticotropin
- adrenal gland releases mg cortisol
- Cortisol end-product feeds back & can inhibit these steps
bottom up signalling requires tissue-specific responses to fuel
- The portal vein carries nutrients to the liver.
- Hepatocytes turn nutrients into fuel.
- Hepatocyte enzymes turn over quickly.
- Enzymes increase or decrease with changes in diet and the needs of other tissues.
