Endocrine Principles Flashcards
Polypeptide and Protein Hormones:
Steroids
Amine Hormones
- Derived from tyrosine
- Include thyroid and adrenal medullary hormones
- Formed by actions of enzymes in cytoplasmic compartments of glandular cells
- Thyroid hormones are incorporated into macromolecules of thyroglobulin and stored in thyroid gland follicles.
- Catecholamines(epinephrine and norepinephrine) are formed in adrenal medulla and stored in vesicles until needed.
Receptor Locations
- In or on the surface of cell membrane
- In the cell cytoplasm
- In the cell nucleus
Down Regulation of Receptors:
Up regulation of receptors
Ion-channel-linked receptors:
- Used primarily by neurotransmitters
- Found in post-synaptic membrane
- Binding leads to conformation change resulting in opening of ion channels such as sodium, calcium, or potassium
G protein-linked hormone receptors:
- Coupled with groups of cell membrane proteins called heterotrimeric GTP-binding proteins.
- All of these receptors have 7 transmembrane segments.
- Some G proteins are inhibitory Gi) and some are stimulatory (Gs).
Intracellular hormone receptors
Intracellular receptors for lipid soluble hormones:
- Adrenal and steroidal hormones
- Thyroid hormones
- Retinoid hormones
- Vitamin D
Activated hormone-receptor complex binds to promoter sequence of DNA: •Hormone response element
Enzyme-linked hormone receptor:
Single-pass transmembrane receptors
Receptor part is extracellular
Intracellular enzyme:
- May be part of the receptor •(intrinsic)
- May be separate from the receptor
Example is the leptin receptor (JAKSTAT)
•Transduction pathway requires tyrosine kinase (JAK family) •Activates transducer proteins (STAT)
Feedback Loops
Example of positive feedback mechanism:
LH surge prior to ovulation:
- Prior to ovulation, estrogen stimulates the surge of LH.
- LH acts on ovaries to secrete more estrogen.
- Secreted estrogen stimulates the release of more LH.
- Additional LH results in typical negative feedback.
Periodic variations in hormone release are superimposed on the negative and positive feedback mechanisms
- Seasonal changes
- Various stages in development and aging
Signal Transduction Mechanisms
- Adenylcyclase—cAMPsecond messenger system
- Cell membrane phospholipid second messenger system
- Calcium—calmodulinphospholipid second messenger system
- Hormones acting directly on DNA
Adenylcyclase—cAMPsecond messenger system
- Binding of hormones with a receptor allows coupling of the receptor to a G protein.
- A G protein that stimulates the adenyl cyclase—cAMPsystem is called a Gs protein.
- Adenylcyclase catalyzes ATP → cAMP.
- cAMPactivates cAMP-dependent protein kinase.
- Protein kinase phosphorylates specific proteins.
- This system typically activates a cascade of enzymes.
- Giproteins reduce the formation of ATP.
Cell membrane phospholipid second messenger system:
In this system, hormones activate transmembrane receptors that activate enzyme phospholipase C.
Phospholipase C catalyzes break-down of phospholipids in the cell membrane:
- Phosphatidylinositol biphosphate PIP2→
- Inositol triphosphate (IP3):
- Mobilizes calcium ions from mitochondria and ER
- Diacylglycerol (DAG):
- Activates protein kinase C
- Note that a component of DAG is arachidonic acid
Calcium—Calmodulin phospholipid second messenger system
- Calcium entry may be initiated by:
- Changes in membrane potential that open calcium channels
- A hormone interacting with membrane receptors that open calcium channels
- Calcium ions bind with calmodulin
- When 3-4 binding sites are filled calmodulininitiates multiple effects:
- Activation of protein kinases
- Inhibition of protein kinases
Hormones acting directly on DNA:
Steroid hormones: •Diffuse across cell membrane •Bind with receptor proteins in cytoplasm •Receptor protein-steroid complex diffuses into nucleus •Complex binds to DNA
Note that this system takes longer than membrane-receptor mediated signaling.
Thyroid hormones: •Bind directly with receptors in nucleus •Activate genetic mechanisms for many (up to 100+) kinds of proteins, many of which enhance metabolic activity. •Note that thyroid hormones, once bound to DNA, remain bound for days to weeks and continue to function.
Anterior Pituitary (Adenohypophysis)
At least five cell types can be differentiated:
- Somatotropes(acidophils): HGF
- Corticotropes: ACTH
- Thyrotropes: TSH
- Gonadotropes: LH and FSH
- Lactotropes: Prolactin
Posterior Pituitary (Neurohypophysis)
Magnocellularneurons are located in the supraopticand paraventricularnuclei.
- ADH is formed primarily in the supraopticnuclei.
- Oxytocin is formed primarily in the paraventricularnuclei: Causes contraction of the pregnant uterus and Aids in milk ejection (milk letdown) by acting on myoepithelial cells of mammary alveoli.
Hypothalamus
Controls anterior pituitary via hormones called hypothalamic releasing and inhibitory hormones (factors).
- Conducted to anterior pituitary via hypothalamichypophysealportal system
- Secreted into median eminence
- Diffuse into portal system
Collecting center for information concerning internal well-being of body
Growth Hormone Functions
Growth, protein synthesis, fatty acid mobilization, decreases glucose utilization, Causes liver to form somatomedins (proteins),
Growth Function
- Increases deposition of protein by chondrocyticand osteogeniccells
- Increases rate of reproduction of chondrocyticand osteogeniccells
- Converts chondrocytes into osteogeniccells
- Strongly stimulates osteoblasts
Protein Synthesis
- Directly enhances transport of amino acids through cell membranes into cytoplasm
- Increases RNA translation
- Increases transcription rate
- Decreases protein catabolism
