Lecture 20: Endocrine Principals Flashcards
Why is negative feedback important for hormone systems?
Negative feedback prevents over-activity of hormone systems.
controlled variable is sometimes not the secretory rate of the hormone itself but the degree of activity of the target tissue
List the different levels in which feedback loop regulation controls hormones.
> gene transcription
gene translation
processing of hormones
releasing of steroid hormones
Give an example of a positive feedback mechanism of hormone control.
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.
List periodic variations in hormone release that are superimposed on the negative and positive feedback mechanisms.
> seasonal changes (more common in other animals, not as much in humans)
> various stages in development and aging (effects humans more)
Where are receptors typically found?
> in or on the surface of cell membrane
in the cell cytoplasm
in the cell nucleus
Define “down regulation” of hormone receptors.
Number of active receptors may decrease because of increased hormone concentration and increased binding to receptors.
Under what conditions may down regulation of hormone receptors occur?
> Inactivation of some of the intracellular protein signaling molecules.
> Temporary sequestration of the receptor inside the cell.
> Inactivation of some of the receptor molecules.
> Destruction of the receptors by lysosomes after they are internalized.
> Decreased production of receptors.
What is the effect of down regulation of hormone receptors?
Down regulation decreases the target tissue’s responsiveness to the hormones.
Define “up regulation” of hormone receptors.
Number of active receptors or intracellular signaling molecules may increase.
Under what conditions may up regulation of hormone receptors occur?
> The stimulating hormone may induce greater than normal formation of receptor or intracellular signaling molecules.
> The stimulating hormone may induce greater availability of the receptor for interaction with the hormone.
What is the effect of up regulation of hormone receptors?
Up regulation increases the target tissue’s responsiveness to the hormones.
What are the two types of receptors we are covering?
> Ion-channel-linked receptors
G protein-linked hormone receptors
Enzyme-linked hormone receptors
Intracellular hormone receptor
What type of signaling molecule primarily uses ion-channel-linked receptors?
Neurotransmitters
What are the characteristics of ion-channel-linked receptors?
used primarily by neurotransmitters
not talking too much about
What are the characteristics of G protein-linked hormone receptors?
> Couple 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).
What are the characteristics of enzyme-linked hormone receptors?
> single-pass trasmembrane receptors > receptor part is extracellular > intracellular enzyme: - may be part of the receptor - may be separate from the receptor > example is the leptin receptor (JAK-STAT) transduction pathway: - requires tyrosine kinase (JAK family) - activates transducer proteins (STAT)
What are the characteristics of 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
What are the 3 classes of hormones?
> Polypeptide and Protein Hormones
Steroids
Amine Hormones
What are the characteristics of polypeptide and protein hormones?
- polypeptide 100 amino acids
- stored in secretory vesicles until needed
- usually synthesized as preprohormones
- released via exocytosis:
> usually mediated via Ca2+ ions - release for some may involve cAMP
What are the characteristics of steroids (hormones)?
- usually synthesized from cholesterol
- lipid soluble and diffuse readily across cell membranes
- consist of three cyclohexyl rings and one cyclopentyl ring
- large quantities of cholesterol esters stored rather than hormones themselves
List some example of common steroid hormones.
> cortisol
aldosterone
testosterone
estradiol
What are the characteristics of 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
What are the four signal transduction mechanisms?
> Adenyl cyclase - cAMP second messenger system.
> Cell membrane phospholipid second messenger system.
> Calcium - calmodulin phospholipid second messenger system.
> Hormones acting directly on DNA.
In the adenyl cyclase - cAMP second messenger system, what effect does Gi proteins have on ATP formation?
Reduces the formation of ATP.
In the adenyl cyclase - cAMP second messenger system, which G protein stimulates this system?
Gs protein
What is the general mechanism in the cell membrane phospholipid second messenger system?
Hormones activate transmembrane receptors that activate enzyme phospholipase C (catalyzes break-down of phospholipids in the cell membrane).
Phospholipase C then cleaves PIP2 into IP3 + DAG.
DAG activates PKC, resulting in cell response.
component of DAG is arachidonic acid
IP3 mobilizes calcium ions from mitochondria and ER, resulting in cell response.
What is the general mechanism in the 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 calmodulin initiates multiple effects:
- activation of protein kinases
- inhibition of protein kinases
What type of hormones act directly on DNA?
- steroid hormones
- thyroid hormones
What are the characteristics of steroid hormone signal transduction acting directly on DNA?
> Diffuse across cell membrane.
Bind with receptor proteins in cytoplasm.
Receptor protein-steroid complex diffuses into nucleus.
Complex binds to DNA.
What are the characteristics of thyroid hormone signal transduction acting directly on DNA?
> 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.
True or False:
Thyroid hormones, once bound to DNA, remain bound for a short period of time.
False - thyroid hormones, once bound to DNA, remain bound for days to weeks and continue to function.
True or False:
Hormones acting directly on DNA take longer than membrane-receptor mediated signaling to occur.
True
What are the 5 cell types that are found in the anterior pituitary (adenohypophysis)?
> Somatotropes (acidophils) > Corticotropes > Thyrotropes > Gonadotropes > Lactotropes
Remember: troph (tropic) means that they will activate/trigger the release of another hormone.
In the anterior pituitary, what do somatotrope cells secrete?
HGF (human growth factor)
In the anterior pituitary, what do corticotrope cells secrete?
ACTH (adrenocorticotropic hormone)
In the anterior pituitary, what do thyrotrope cells secrete?
TSH (thyroid stimulating hormone)
In the anterior pituitary, what do gonadotrope cells secrete?
LH (luteinizing hormone) and FSH (follicle stimulating hormone)
In the anterior pituitary, what do lactotrope cells secrete?
Prolactin
Review figure 76-2 and text for metabolic functions of the anterior pituitary hormones.
Keep working hard! You’ve almost made it!!
Which two hormones released from the anterior pituitary gland will directly or indirectly increase blood glucose levels?
- Human Growth Factor (HGF - from somatotropes) (directly)
- Adrenocorticotropic Hormone (ACTH - from corticotropes) (indirectly - stimulates adrenal cortex to release ACH, which increases blood glucose level)
In the posterior pituitary (neurohypophysis), in which nuclei are magnocellular neurons located?
- supraoptic nuclei
- paraventricular nuclei
Which two hormones are released from the posterior pituitary?
- ADH
- Oxytocin
In which nuclei is ADH formed?
Supraoptic Nuclei
In which nuclei is oxytocin formed?
Paraventricular Nuclei
What does oxytocin cause?
> Causes contraction of the pregnant uterus.
> Aids in milk ejection (milk letdown) by acting on myoepithelial cells of mammary alveoli.
What type of cells does oxytocin act on to aid in milk ejection (milk letdown)?
Myoepithelial cells of mammary alveoli.
Which nuclei primarily makes oxytocin?
paraventricular nucleus
Which nuclei primarily makes ADH?
supraoptic nucleus
What does the hypothalamus control?
Controls anterior pituitary via hormones called hypothalamic releasing and inhibitory hormones (factors).
> conducted to anterior pituitary via hypothalamic-hypophyseal portal system
secreted into median eminence
diffuse into portal system
hypothalamus is the collecting center for information concerning internal well-being of the body
What is the hypothalamus?
A collecting center for information concerning internal well-being of the body.
List sequentially the components of the hypothalamic-pituitary axis.
artery -> primary capillary plexus (in the median eminence) -> hypothalamic-hypophysial portal vessels -> sinuses (in the anterior pituitary) -> veins
How does growth hormone function to increase growth?
> Increases deposition of protein by chondrocytic and osteogenic cells.
> Increases rate of reproduction of chondrocytic and osteogenic cells.
> Converts chondrocytes into osteogenic cells.
> Strongly stimulates osteoblasts.
How does growth hormone function to increase protein synthesis?
> Directly enhances transport of amino acids through cell membranes into cytoplasm.
> Increases RNA translation.
> Increases transcription rate.
> Decreases protein catabolism.
What effect does growth hormone have on fatty acid mobilization?
> Causes release of fatty acids from adipose tissue.
> Enhances conversion of fatty acids to actyl-CoA.
What effect does growth hormone have on glucose?
Decreases glucose utilization
> Decreases glucose uptake in tissues such as skeletal muscle and fat.
> Increases glucose production by liver.
> Increases insulin secretion.
> Note: GH’s effects are diabetogenic.
What does growth hormone cause the liver to do, besides increase glucose production?
Causes liver to form somatomedins (proteins).
> powerful effect on all aspects of bone growth
> similar to effects of insulin on growth
> also called insulin-like growth factors (IGFs)
> most important is somatomedin C (IGF-I)
What is the most important somatomedin (IGFs) formed by the liver after stimulation by growth hormone?
Somatomedin C (IGF-I)
True or False:
Injection of growth hormone in to epiphyseal plates causes specific growth of these regions.
True
List factors that are known to stimulate secretion of growth hormone.
> Starvation (protein deficiency)
> Hypoglycemia
> Exercise
> Excitement
> Trauma
> Ghrelin (the “hunger hormone”, also known as lenomorelin (INN), is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract[1][2] which functions as a neuropeptide in the central nervous system.[3] Besides regulating appetite, ghrelin also plays a significant role in regulating the distribution and rate of use of energy).
> First two hours of deep sleep
What does kwashiorkor mean?
Malnutrition produced by a severely inadequate amount of protein in the diet.
