Hormones

Question 1

metabolism at the organism level

Answer 1

• role and structure of specific tissues and organs
• flux of metabolites from organ to organ
• hormonal regulation of metabolism
• control of body mass

Question 2

neuronal vs hormonal signalling

Answer 2

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).

Question 3

hormone-receptor interactions

Answer 3

• 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.

Question 4

5 types of downstream events following hormone binding

Answer 4

1. A secondary messenger (cAMP; inositol triphosphate, IP3) is released inside the cell: allosterically regulates enzymes
2. A receptor Tyr kinase is activated.
3. A hormone-gated ion channel is opened or closed: resulting in changes in membrane potential
4. A steroid bound to receptor protein in the nucleus alters gene expression: resulting in changes in membrane potential
5. An adhesion receptor sends information to the cytoskeleton.

Question 5

hormones: extracellular vs intracellular

Answer 5

act on: cell surface receptor (doesn't enter cell)
or
nuclear receptor (acts internally)

Question 6

peptide and amine hormones bind extracellularly

Answer 6

• 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.

Question 7

3 classes of mammalian hormones

Answer 7

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)

Question 8

additional classification based on hormones chemical structure

Answer 8

membrane receptor: peptide, catecholamine, eicosanoid

nuclear receptor: steroid, vitamin D, retinoid, thyroid

cytoplasmic receptor: nitric oxide

Question 9

peptide hormone insulin

Answer 9

• 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)

Question 10

role of insulin

Answer 10

• 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.

Question 11

conversion of glucose –> glycogen or TAGs

Answer 11

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

Question 12

some peptide pro-hormones can yield multiple products

Answer 12

• 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

Question 13

Catecholamine hormones: epinephrine and norepinephrine

Answer 13

• 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)

Question 14

Eicosanoid hormones

Answer 14

• 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

Question 15

Steroid hormones made from cholesterol

Answer 15

• 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.

Question 16

Vitamin D hormones (nuclear receptor)

Answer 16

• 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.

Question 17

Retinoid hormones (nuclear receptor)

Answer 17

• 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

Question 18

thyroid hormones (nuclear receptor)

Answer 18

• 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.

Question 19

Nitric oxide interacts (intracellular receptor)

Answer 19

• 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

Question 20

major endocrine glands

Answer 20

• Brain: hypothalmus, pituitary
• Thyroid, parathyroid
• Adipose (fat) tissue
• Adrenals (on top of the kidneys)
• Pancreas
• Ovaries/Testes

Question 21

top down vs bottom up hormonal signalling

Answer 21

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

Question 22

hypothalamus

Answer 22

• 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.

Question 23

pituitary release of hormones target other glands

Answer 23

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

Question 24

posterior pituitary hormones: oxytocin and ADH

Answer 24

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

Question 25

hypothalamic cortisol cascade

Answer 25

• 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

Question 26

bottom up signalling requires tissue-specific responses to fuel

Answer 26

• 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.