Hormone Action: Biochemistry

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Proteins and glycoproteins

Water Soluble or Lipid Soluble Hormones?

Water Soluble

Peptides

Water Soluble or Lipid Soluble Hormones?

Water Soluble

Catecholamines

Water Soluble or Lipid Soluble Hormones?

Water Soluble

Steroids and Vitamin D

Water Soluble or Lipid Soluble Hormones?

Lipid Soluble

Retinoids

Water Soluble or Lipid Soluble Hormones?

Lipid Soluble

Thyroid hormones

Water Soluble or Lipid Soluble Hormones?

Lipid Soluble

Water Soluble Hormones:
1. Where are the receptors found?
2. Once they bind to the receptor, how do they initiate their action?
3. Quick or slow response?
4. Name some examples of water soluble hormones

1. Receptors found on cell membrane
2. Utilizes secondary messenger
3. Quick response (minutes)
4. Examples: Insulin, Glucagon, Neurotransmitters

Fat Soluble Hormones:
1. Where are the receptors found?
2. Once they bind to the receptor, how do they initiate their action?
3. Quick or slow response?
4. Name some examples of lipid soluble hormones

1. Receptors found inside the cell
2. Hormone receptor complexes activate transcription in the nucleus
3. Slow response (usually hours)
4. Examples: Estrogen, Testosterone, Fat-Soluble vitamins (A,D)

Insulin, Glucagon

Water soluble or lipid soluble hormones?

Water soluble

Neurotransmitters

Water soluble or lipid soluble hormones?

Water soluble

Estrogen, Testosterone

Water soluble or lipid soluble hormones?

lipid soluble

Vitamins A, D, E, K

Water soluble or lipid soluble hormones?

lipid soluble

Lipid soluble hormones often hitch a ride on what molecule?

albumin

Hormone: Amine (epinephrine)

-Water soluble or lipid soluble?
-Receptor location?

Class: Water-soluble
Receptor location: Cell surface

Hormone: Amine (thyroid hormone)

-Water soluble or lipid soluble?
-Receptor location?

Class: Lipid soluble
Receptor location: Intracellular

Hormone: Peptide/protein (Insulin)

-Water soluble or lipid soluble?
-Receptor location?

Class: Water soluble
Receptor location: Cell surface

Hormone: Steroids Retinoids and Vitamin D

-Water soluble or lipid soluble?
-Receptor location?

Class: Lipid Soluble
Receptor location: Intracellular

Which type of intracellular receptor?

-Located in the nucleus
-Associated with gene expression

Nuclear Receptors

Which type of intracellular receptor?

-Located in the cytoplasm
-Translocate to the nucleus after binding
-Associated with gene expression

Steroid Receptors

Which type of intracellular receptor?

Associated with the production of cGMP

Soluble nitric oxide (NO) receptors

Which type of membrane receptor?

Tyrosine kinase autophosphorylation receptors

Insulin and Insulin-like Growth Factor Receptors

Which type of membrane receptor?

Similar to insulin-like receptors except there is no autophosphorylation

Jak-Stat Receptors (the Jak enzyme does the phosphorylation rather than autophosphorylation)

Which type of membrane receptor?

Similar to insulin-like receptors except the autophosphorylation goes onto serines and threonines rather than tyrosines

Serine/Threonine Receptors

Which type of membrane receptor?

Produce cGMP directly

Enzyme Receptors

Which type of membrane receptor?

Trimeric G-protein linked

Heptahelical-Serpentine Receptors

Which pancreatic hormone?
-β-cells
-Anabolic, energy storage

Insulin

Which pancreatic hormone?
-α-cells
-Catabolic, energy mobilization

Glucagon

Which pancreatic hormone?
-δ-cells
-Resists change

Somatostatin

Insulin
1. A water soluble peptide hormone (51 AA's)
2. Released from beta cells of the pancreas in which state? (fed or fasting?)
3. Has endocrine (acts at a distance) action at which three organs/tissues?
4. Has paracrine action on the alpha cells of the pancreas by suppressing release of what hormone?
5. The insulin receptor is a _________________ receptor that has __________activity. (what type of receptor?)

1. A water soluble peptide hormone (51 AA's)
2. Released from beta cells of the pancreas in fed state
3. Endocrine action at the muscle, adipose and liver.
4. Suppressing glucagon release.
5. The insulin receptor is a cell surface receptor that has autocatalytic tyrosine kinase activity.

Insulin
1. Promotes growth and storage of molecules
-Stimulate synthesis of _______ (liver and muscle)
-Stimulate synthesis of _________ (liver)
-Stimulates synthesis of _________ from fatty acids (liver and adipose)
-Stimulate synthesis of over 50 ______

2. Is considered a growth factor

3. Similar to the somatomedins (insulin-like growth factors)

4. Insulin promotes gene expression of enzymes related to insulin's actions and directly turns on the upregulation of which channel in muscle and fat & glycogen synthesis in liver and muscle?

1. Promotes growth and storage of molecules
-Stimulate synthesis of glycogen (liver and muscle)
-Stimulate synthesis of fatty acids (liver)
-Stimulates synthesis of triglycerides from fatty acids (liver and adipose)
-Stimulate synthesis of over 50 proteins

2. Is considered a growth factor

3. Similar to the somatomedins (insulin-like growth factors)

4. Glut4

Insulin:
1. promotes _________ uptake in muscle and adipose
2. ________ synthesis in liver and muscle
3. __________ synthesis in liver
4. ____ synthesis in liver and adipose
5. _____ synthesis in muscle

1. promotes glucose uptake in muscle and adipose
2. glycogen synthesis in liver and muscle
3. fatty acid synthesis in liver
4. TG synthesis in liver and adipose
5. protein synthesis in muscle

Glucagon:
1. What type of hormone is it? (water soluble or lipid soluble?)
2. Where are glucagon receptors located?
3. Where is glucagon produced?
4. What is the plasma half-life of pancreatic glucagon?
5. Glucagon is counter regulatory to which hormone?
6. Stimulates breakdown of ______, activation of gluconeogenesis and the release of glucose to the blood (all in the liver)
7. Inhibits synthesis of fatty acids (in the liver) and promotes synthesis of ____________ in the liver
8. Interestingly, it promotes the release of _________(which inhibits glucagon release)

1. A water soluble peptide hormone
2. Binds to surface receptors on the liver
3. Produced in the alpha cells of the pancreas and the L cells of the intestine
4. 3-6 minutes
5. insulin
6. glycogen
7. ketone bodies
8.insulin

When a Trimmeric G-Protein is activated, Adenylate Cyclase produces _____ until the GTP hydrolyses back to GDP and then process stops

cAMP

cAMP activates _______ and leads to numerous cellular effects including directly affecting sugar metabolism and indirectly affecting metabolism through changes in gene expression.

PKA

Glucagon acts through which second messenger?

Gα-s
Increases cAMP

Somatostatin:

1. Released by the _________, the _____ cells of the pancreas, many areas of the CNS, and gastric & duodenal mucosal cells
2. Inhibits release of several things. Name a few
3. ______________ visceral blood flow. (↑or ↓?)
4. Release of somatostatin is stimulated by glucose, arginine, leucine, glucagon, vasoactive peptide (VIP), cholecystokinin (CCK)
5. 5 subtypes of receptors, all linked to which G protein?

1. Released by hypothalamus, the Delta cells of the pancreas, many areas of the CNS, and gastric & duodenal mucosal cells
2. Inhibits release of
-growth hormone and thyroid stimulating hormone (from anterior pituitary)
-Insulin and glucagon (from pancreas)
-Pancreatic exocrine secretions (digestive enzymes)
-Gastrin (this decrease prolongs gastric emptying time)
3. Decreases visceral blood flow.
4. Release stimulated by glucose, arginine, leucine, glucagon, vasoactive peptide (VIP), cholecystokinin (CCK) --> fed state
5. All linked to Gαi

Synthetic analogs of this hormone are used clinically to treat secretory neoplasms such as GH-secreting tumors of the pituitary (gigantism and acromegaly)

somatostatin

Growth Hormone:

1. Plasma half-life
2. Where is GH secreted by?
3. Acts directly on cells as well as inducing production of ____________ in the liver
4. Similar to insulin receptors, these systems use what type of receptors?
5. Release of GH is stimulated by ____________
6 Release of GH is inhibited by what two things?
7. Affects uptake and oxidation of fuels in adipose, muscle and liver.
8. Increases availability of fatty acids by increasing the sensitivity of adipose tissue to catecholamines (DA, NE and Epi) and decreases sensitivity to insulin

1. 20-50 minutes
2. the somatotroph cells of the lateral anterior pituitary
3. IGF-I (insulin like growth factor - I)
4. tyrosine kinase
5. GHRH (growth hormone releasing factor)
6. GHRIH (growth hormone release inhibiting factor, better know as somatostatin) AND IGF-I, produced primarily in the liver in response to GH (feedback inhibition)

Growth hormone has what affect on each of these organs:

Liver
1. IGF-1 (↑or ↓?)
2. Gluconeogenesis (↑or ↓?)
3. Glycogen Synthesis (↑or ↓?)

Adipose tissue
1. synthesis of fats or lipolysis?

Muscle
1. Glucose uptake (↑or ↓?)
2. protein synthesis (↑or ↓?)

Liver
1. IGF-1 ↑
2. Gluconeogenesis ↑
3. Glycogen Synthesis ↑

Adipose tissue
1. Lipolysis

Muscle
1. Glucose uptake ↓
2. protein synthesis ↑

Catecholamines
1. Epinephrine is primarily produced where?
2. Norepinephrine is produced where?
3. Dopamine is primarily made where?
4. All three are made from which amino acid?
5. What is the pathway for the production of these three hormones?
6. Epi and NE are released by the adrenal medulla in response to what?

1. in the adrenal medulla
2. in the adrenals and the nervous system
3. in the brain
4. tyrosine
5. Tyr --> l-Dopa --> DA --> NE --> Epi
6. stress (pain, hemorrhage, exercise, hypoglycemia, and hypoxia).

Epinephrine:

1. Epi is the major player that stimulates the releases of which hormone?
2. Epi enhances _________ in muscle tissue
3. Epi enhances ___________ in the liver
4. Epi increases the amount of ______ released into the blood

1. growth hormone
2. metabolism
3. gluconeogenesis
4. glucose

What specific type of receptor does Epi bind to?

Epi receptor is a heptahelical serpentine receptor, coupled to a trimmeric G-protein

When Epi binds to a β receptor, what are the downstream effects?

1. Beta 1, 2 or 3 --> Coupled to Gαs
2. Activates synthesis of cAMP --> activates PKA
3. This increases the release of glucose into the blood

The epinephrine β-receptor is very similar to which other hormones receptor?

glucagon

When Epi binds to an α-1 receptor, what are the downstream effects?

•Alpha-1 receptors act through Gαq system
•The enzyme phospholipase C is activated by the trimmeric G-protein. PLC cleaves PIP2 into DAG and IP3
•IP3 activates the release of calcium from the endoplasmic reticulum
•DAG activates PKC

Ultimately releases glucose into the blood

When Epi binds to an α-2 receptor, what are the downstream effects?

Act through Gαi receptors
Counteract the betas
Will decrease cAMP, decrease PKA activation and stop glucose from being released into the blood

Glucocorticoids
1. An insulin counter regulatory hormone
2. Released in response to _____
3. ACh and 5-HT induced release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus.
4. ____ induces pituitary to release ACTH.
5. ACTH induces adrenal gland to convert cholestrol into pregnenolone, which then is then converted into the _______________, including cortisol.
6. Cortisol inhibits release of both _____ and _____

2. stress (pain, hypoglycemia, hemorrhage and exercise)
4. CRH
5. adrenal steroid hormones
6. CRH and ACTH.

Where are glucocorticoid receptors located?

Their receptors are cytoplasmic but then they translocate to the nucleus and have their activity there by affecting gene regulation

Effects of glucocorticoids
1. Mobilize _____ from the liver and adipose
2. Mobilize the release of_____ from the muscle
3. Activate which metabolic process in the liver?
4. Activate the storage of glucose as _______

1. Mobilize FFAs from the liver and adipose
2. Mobilize the release of AAs from the muscle
3. Activate gluconeogenesis in the liver
4. Activate the storage of glucose as glycogen

In contrast to Epi which will break down the glycogen and release that glucose back in the blood

Effects of glucocorticoids

Muscle
1. Protein degrdation (↑or ↓?)
2. Protein synthesis (↑or ↓?)
3. Glucose utilization (↑or ↓?)

Adipose
1. lipolysis (↑or ↓?)
2. glucose utilization (↑or ↓?)

Liver
1. Gluconeogenesis (↑or ↓?)
2. Glycogen storage (↑or ↓?)

Muscle
1. Protein degrdation ↑
2. Protein synthesis ↓
3. Glucose utilization ↓

Adipose
1. lipolysis ↑
2. glucose utilization ↓

Liver
1. Gluconeogenesis ↑
2. Glycogen storage ↑

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