Hormones and Integrated Metabolism Flashcards
Neuronal Signaling VS. Hormonal Signaling
Neuronal Signaling:
- release transmitters that act on nearby cells (small distance)
Hormonal Signaling:
- hormones are carried by bloodstream to nearby cells or other organs (long distance)
What is the challenge in detecting hormones? What was developed as a way to measure hormones?
- Challenge in detecting: Hormones are produced in small amounts -> hard to purify in appreciable quantity
- RIA (radioimmunoassay): more sensitive way to measure hormones using radiolabeled antibodies
Features of Hormone-Receptor Interactions
- Specific Interactions
- High affinity: only low amounts of hormone are needed
- Different types of cells have different receptors
- Different cells with same receptor can have different downstream effects
- Similarly structured hormones can bind different receptors
What are the three classes of hormones based on pathway from release to target?
Classification based on path from release -> target
1) Paracrine: released into extracellular space to neighboring target (ex: eicosanoids)
2) Endocrine: released to blood, carried to target cells (ex: insulin, glucagon)
3) Autocrine: affects the cell where they are produced
- Binds to surface receptors
What are the five types of “downstream” events that happen following hormone binding?
1) Secondary messenger (cAMP, IP3) is released inside the cell: allosterically regulates enzymes
2) Tyr kinase receptor is activated
3) Hormone-gated ion channel is open or closed -> causes changes in membrane potential
4) Adhesion receptor (ligands, adhesions) sends info to the cytoskeleton -> promote movement/growth
5) Steroid (that’s bound to receptor protein in nucleus) alters gene expression -> acts as a transcription factor b/c it can go through nuclear membrane
Extracellular and Intracellular Hormones
Extracellular: Cell surface receptors
- Can be metabotropic or ionotropic
- Hormone binds to receptor on outside of cell and acts though the receptor (doesn’t enter cell)
Intracellular: Nuclear receptors
- Steroid or Thyroid hormone enters cell, acts in the nucleus
What are the 8 classes of hormones based on chemical structure?
Plasma membrane receptors; 2nd messengers:
1) Peptide: Insulin, Glucagon
2) Catecholamine: Epinephrine
3) Eicosanoid: Prostaglandin E2
Nuclear receptors; transcriptional regulation:
4) Steroid: Testerone
5) Vitamin D: Calcitriol
6) Retinoid: Retinoic acid
7) Thyroid: T3
Cytosolic receptor and cGMP:
8) Nitric Oxide
What hormones are made from peptide and amine? (Insulin, Epinephrine)
Insulin: peptide hormone
Epinephrine: amine hormone
- Binds to receptors that span the membrane (on outside) and cause conformation change that produces a 2nd messenger -> results in signal amplification
How is Insulin (peptide hormone) produced? Where is insulin stored?
- Synthesized on ribosome of beta cells as preproinsulin and processed into insulin
- Stored in secretory vesicles in beta cells
Why is Insulin made? What receptors do Insulin bind to?
Insulin is made in response to increased blood glucose levels. It binds to receptors in the muscle, brain, liver, adipose tissues, other tissues.
What is the role of insulin in muscles, liver, and adipocytes?
- In muscle: facilitates glucose uptake
- In liver: promotes glycogen synthesis
- In adipocytes: promotes glycerol synthesis and inhibits breakdown of fats
What products does POMC (Pro-Opiomelanocortin) make? (peptide pro-hormones can make multiple products)
- Has at least 8 different cleavage sites
- Produces at least 10 different peptide hormones
- Mutations in POMC are associated with obesity
What hormones are made from catecholamine?
Epinephrine and Norepinephrine
- Synthesized in adrenal glands from L-tyrosine (AA)
- Concentrated in storage vesicles and released
- Binds to extracellular receptors to generate secondary messengers
(Tyrosine -> Dopamine -> Norepinephrine -> Epinephrine)
What hormones are made from Eicosanoid?
Prostaglandins, Thromboxanes, Leukotrienes
- Not made in advanced: made when needed from arachidonic acid via phospholipase A2
- They are paracrine hormones (act nearby)
- Role in inflammation, smooth muscle contraction and platelet function
What hormones are made from Cholesterol?
Steroids: Cortisol, Testosterone, Estradiol
- binds to carrier proteins, travel through bloodstream
- enters the cell nucleus and binds to nuclear receptors (acting as transcription factor) to alter gene expression
(Cholesterol -> Progesterone -> Steroids)
What type of receptor does Vitamin D hormone bind to?
Nuclear receptor
- Vitamin D is obtained from good or sun exposure
- Active form of Vitamin D: calcitrol
- Affects the transcription of genes that regulate Ca2+ and the balance between Ca2+ deposition and removal from bone
What causes Rickets?
Lack of vitamin D
What type of receptors do Retinoid hormones bind to?
Nuclear receptors
- Retinoid hormones come from vitamin A1 (retinol) which is from b-carotene
- All cells have at least 1 form of retinoid receptor
- Hormone-receptor complex regulates genes that have roles in cell growth and differentiation
What type of receptors do Thyroid hormones bind to?
Nuclear receptors
Thyroglobulin (precursor) makes T4, which is converted to T3
- T3: has 3 iodines at Tyr residues
- T4: has 4 iodines at Tyr residues
Receptor-Hormone complex increases expression of enzymes that yield energy
What type of receptor does Nitic Oxide interact with?
Intracellular receptor
NO: free radical made from arginine and O2, by the enzyme NO synthase
- acts locally (near point of its release)
- enters target cell and activates guanylyl cyclase to increase cGMP -> activation of cGMP-dependent protein kinase, relaxation of contractile protein in smooth muscle of blood vessels (lowers blood pressure)
What are the major endocrine glands?
- Brain: hypothalamus, pituitary
- Thyroid, Parathyroid
- Adipose (fat) tissue
- Adrenals (on top of kidneys)
- Pancreas
- Ovaries/Testes
What is Top Down vs. Bottom Up hormone signaling?
Top-Down signaling:
- signals start in the brain and sent out to the body (ex: oxytocin, cortisol, etc)
Bottom-Up signaling:
- signals start from somewhere in the body and send messages to the brain (ex: epinephrine (adrenaline), insulin)
What is the hypothalamus?
It is the coordination center of the epinephrine system. It is located in the forebrain.
- Receives and integrates nerve signals from the CNS
- Synthesizes peptide hormones: oxytocin, vasopressin
- Synthesizes factors that regulate the function of the anterior pituitary
What is the pituitary?
The release of hormones from the pituitary targets other glands.
1) Posterior pituitary (neurohypophysis): goes into blood vessels
- has ends of axons from the hypothalamus
- holds short peptide hormones made in hypothalamus
2) Anterior pituitary (adenohypophysis): receives signals from bloodstream
- endocrine organ that receives releasing factors from the hypothalamus via blood vessels
- makes tropins (long peptide hormones)
- activates second targets: adrenal cortex, thyroid, ovaries/testes