Endocrine Flashcards
What are the three chemical structure classifications of hormones?
- Proteins/polypeptides (insulin) 2. Steroids (cortisol) 3. Tyrosine amino acids (epi/norepi)
What are some examples of steroid hormones?
Cortisol, aldosterone, testosterone, estradiol
What are characteristics of the amine hormones?
Adrenal medulla hormones: derived from tyrosine, epi is made 4x as more as norepi. stored in vesicles
Thyroid hormone are SYNTHESIZED and STOREd in the thyroid gland. STORED WITH THYROGLOBULINS. Hormone secretion occurs with amines split from the thyroglobuline and free hormones are released into the plasma. Then they bind to PLASMA PROTEINS in the blood to their target tissues.
What is an example of positive feedback?
LH surge occurring right before ovulation. It is a positive feedback resulting from estrogen on the anterior pituitary. LH then acts on ovaries and causes more estrogen secretion.
How to peptides and catecholamines get to their targets?
they are water soluble dissolved in plasma
How to steroid and thyroid hormones get around?
bound to plasma proteins, they are inactive, they have longer duration of actions.
How are hormones cleared?
metabolic destruction by the tissues, binding with tissues, excretion by the liver into bile, urine. Protein bound hormones are cleared slower.
What receptors are on/in the surface of cell membranes?
Proteins and catecholamines
What receptors are in the cytoplasm?
steroids (HRC)
What receptors are in the nucleus?
thyroid
How do we down regulate receptors?
inactivate molecules, intracellular protein signaling molecules, sequestration of receptor away from site of action, destruction of receptor by lysosomes, decreased production of receptors
What is the HRC?
When the hormone affects its target tissues by forming a complex. This alters the function of the receptor itself, activated hormone receptor initiates the hormonal effect. 1. ion channel linked, G protein linked, and enzyme linked.
What binds to ion channel-linked receptors?
acetylcholine, norepinephrine, virtually all the neurotransmitter substances.
What are characteristics of G protein linked hormone receptors?
7 transmembrane segments, trimeric subunits, conformational changes result in downstream activity (opens or closes ion channels, changes activity on a cytoplasmic enzyme)
What are characteristics of enzyme-linked hormone receptors?
only pass through once. LEPTIN receptor -> signals through a tyrosine kinase of the janus kinase family, JAK and JAK 2. which activates the STAT transcription proteins to initiate protein synthesis.
What hormones bind inside the cell/nucleus to intracellular hormone receptors to activate genes?
adrenal, gonadal steroid hormones, thyroid hormones, retinoid hormones, vitamin D. lipid soluble hormones! the HRC complex binds to the promoter HRE. Which activates or represses gene or DNA/mRNA.
What are the types of second messengers?
cAMP; calcium ions/ calmodulin, phospolipid breakdown materials.
How does ca-calmodulin second messenger system work?
calcium binds calmodulin once it enters the cell, calmodulin changes shape and activates or inhibits protein kinases. Activates myosin light chain kinase which causes smooth muscle contraction.
How does the phospholipid second messenger system work?
Activation of the receptor activates the G protein that activates the phospholipase C, catalyzes the breakdown of PIP2 into IP3 and DAG. IP3 mobilized CALCIUM which is a second messenger itself. DAG activates PKC, which is a precursor for local hormones like prostaglandins.
What class of hormones increases PROTEIN synthesis?
steroid hormones
How do steroid hormones work?
Steroid hormone diffuses across cell membrane, where it binds to a receptor protein, then this combo protein gets transported into the nucleus. Then it binds the DNA which activates transcription of mRNA. mRNA diffuses into the cytoplasm where it gets translated by ribosomes to new proteins.
What class of hormones increases gene transcription in the cell nucleus?
thyroid hormones: thyroxine and triiodothyronine. They 1) activate formation of many proteins 2: enhance cellular metabolic activity in virtually all cells of the body
What do somatotrope cells in the pituitary release?
hGH
What does growth hormone do?
promotes growth of the entire body by affecting protein formation, cell multiplication, cell differentiation
What do the adrenal cortical hormones do?
Affect metabolism of glucose, proteins, fats
Prolactin
Promotes mammary gland development and mild production
What are the two hormones produced by the posterior pituitary?
ADH, Oxytocin
ADH- stimulates H2O reabsorption by renal collecting ducts
Oxytocin- milk ejection and uterine contraction
What does FSH and LH do?
FSH: stimulates development of ovarian follicles, estrogen secretion, regulates spermatogenesis
LH: causes ovulation and formation of the corpus luteum, stimulates testosterone and estrogen/progesterone production.
What hormones are released by the anterior pituitary?
hGH, ACTH, TSH, LH, FSH, PRL
What does ACTH do?
Secreted by the AP; Stimulates synthesis and secretion of adrenal cortical hormones (cortisol)
TSH
Released by AP, stimulates synthesis and secretion of thyroid hormones
Controls the rate of secretion of thyroxine, triiodothyronin by the thyroid gland, which control the rates of most chemical reactions in the body.
T3, T4
increases skeletal growth, increases O2 consumption, heat production, increase protein, fat, carb use.
Where are glucocorticoids released from?
ADRENAL CORTEX! Stimulates gluconeogenesis; stimulated by ACTH.
What hormones are secreted by the hypothalamus?
CRH, TRH, GnRH, PIH/PRF, GHRH/SS
How does the hypothalamus communicate with the posterior pituitary?
By nerves that terminate in the posterior pituitary (hypothalamus makes the oxytocin and the ADH)
What are the cell types in the anterior pituitary that secrete hormones?
somatotropes (hGH), corticotropes, thyrotropes, gonadotropes, lactotropes
How are the AP hormones released?
hypothalamic inhibitory or hypothalamic releasing factors are secreted within the hypothalamus and conducted to the anterior pituitary through the hypothalamic hypophysial portal vessels.
Actions of GH?
decrease glucose uptake by cells (diabetogenic), increase lipolysis, increase protein synthesis, increase IGF. increases mobilization of fatty acids, uses up fat stores, and conserves carbohydrates; assists uptake of amino acids with reduction of breakdown of proteins, prevents catabolism of proteins, increased nuclear transcription of DNA to form RNA; INCREASED LIPOLYSIS, INCREASED GLUCONEOGENESIS which causes release of IGFI, which goes to the kidneys, which causes decreased gluconeogensis (negative feedback) long loop! target tissue says enough.
What does IGF-1 do?
Increases glucose transport to the muscle, and muscles efficiently use the carbohydrates and build the muscle mass. Negative feed back occurs when the liver produces the IGIF and tells the kidneys to stop gluconeogenesis, and then the liver stops gluconeogenesis too.
GH peaks when?
at adolescence.
What does IGF do?
increase protein synthesis, increase muscle mass and lean body mass, increase organ size.
What is GH secretion stimulated by?
starvation (protein levels), hypoglycemia or low fatty acids in the blood, exercise, excitement, trauma, Ghrelin
What is another name for GHIH?
Somatostatin
Where is IGF-1 created?
Liver and it stimulates the hypothalamus to release somatostatin to stop the GH from being further released.
What are GH’s effects on carbohydrate metabolism?
decrease glucose uptake in skeletal muscle, increased glucose production by liver, increased insulin secretion.
GH causes what effect on insulin?
insulin resistance, decreased glucose utilization by the cells.
What two things are necessary for GH to work?
insulin and carbohydrates, insulin transports amino acids into cells
What are insulin like growth factors? IGF?
somatomedins, produced by the liver which affect bone growth.
Is GH acting back on the AP short or long loop?
short
What is produced more, thyroxine or triiodothyronin?
THYROXINE (93%), most of the thyroxine is converted to T3.
Which is more potent, T3 or T4?
T3, present in smaller quantities, shorter duration of action, four times as potent
Describe the anatomy of the thyroid gland?
follicles with colloid made of thyroglobulin, thyroglobulins contain thyroid hormones, lined with cuboidal epithelial cells that secrete into the follicles.
What helps with iodination and coupling?
peroxidase
What/where is NIS?
BL sodium iodide symporter
What is pendrin?
Pendrin is an active transporter that exchanges cl for iodine
What contains the tyrosine amino acids in the thyroid cell?
thyroglobulin
After the TH enters the blood what happens?
It binds with plasma proteins: thyroxine binding globulin (mostly), thyroxine binding pre albumin, albumin. Also, t4 gets turned into T3
Where do TH bind to in the target cells?
In the DNA in the nucleus. The TH receptor forms a heterodimer with retinoid X receptor at the thyroid response elements on the DNA. This activates receptor and initiates the transcription process.
What two things combine on the thyroid hormone response element?
Thyroid hormone receptor and the retinoid X receptor
Does the thyroid gland secrete more T3 or T4?
T4 (90%)
Does T3 or T4 down regulate TRH receptors on the anterior pituitary?
T3, which inhibits TSH secretion
Target tissues convert T? to T?
T4 to T3. (Iodinase) and then T3 has the negative feed back effect on the AP.
Does the adrenal cortex or adrenal medulla produce catecholamines?
medulla (epi and norepi)
What does the cortex produce?
- mineralcorticoids (ALDOSTERONE- affect the electrolytes) 2. corticosteroids/glucocorticoids (aldosterone and cortisol) 3. adrogenic hormones (to a lesser extent)
What cells secrete aldosterone?
Zona glomerulosa
What are the layers of the cortex?
zona glomerulosa, zona fasciculata (cortisol), zona reticularis then medulla (fasciculata and reticularis produce glucocorticoids and androgens)
What is the major mineralocorticoid secreted by the adrenal gland?
aldosterone (90%), but there is more cortisol in the plasma. Aldosterones mineralocorticoid activity is 3000 times greater than that of cortisol tho.
What are aldosterones effects?
increases renal tubular reabsorption of sodium and excretion of potassium, causes H ion secretion and alkalosis
Regulation of aldosterone?
- increased K concentration increases aldosterone secretion
- increased ang II increases aldosterone secretion
- increased sodium ion concentration slightly decreases aldosterone secretion
- ACTH from anterior pituitary is necessary for controlling aldosterone secretion.
* K levels and RAAS are the most important mechanisms.
What two states trigger aldosterone release?
Hypovolemia and Hyperkalemia (a direct activator of aldosterone)
Aldosterones effect on sodium?
Na gets reabsorbed while potassium is secreted in the principle cells of the renal collecting tubules
Aldosterone and the intercalated cells?
Aldosterone causes secretion of hydrogen ions in exchange for sodium in the intercalated cells of the cortical collecting tubules (decreases the H concentration and causes a metabolic acidosis)
Describe the pathway of cortisol release?
Circadian rhythm or stress causes CRH to be released from the hypothalamus, to the AP which releases SCTH, this acts on the adrenal cortex to release cortisol.
What does cortisol act on?
- Immune system 2. Liver (gluconeogenesis) 3. Muscle (protein catabolism) 4. Adipose tissue (lipolysis= increased free fatty acids)
What is the biggest trigger for cortisol release?
Stress. cortisol is diurnal
How much cortisol is bound to plasma proteins?
90-95%, long half life of 60-90 mins
What proteins does cortisol bind to?
cortisol binding globulin, transcortin, albumin (lesser extent)
How much aldosterone binds to plasma proteins
60%; short half life of 20 mins; travels in bound and free form
What is the normal ionized calcium concentration?
1.2 mmol/L; iCa is HALF the total plasma calcium concentration
What goes with intercalated cells/ principle cells
Intercalated cells in late distal tubule and collecting ducts- increased H secretion and principal cells increase K secretion in the late distal tubule and collecting ducts
How is PTH secretion controlled?
By Ca binding to Ca sensors on parathyroid membrane; decreased Ca increases PTH secretion. Results in increased Ca and decreased phosphate. Also stimulates kidneys to conserve Ca and rid phosphate, and intestines to absorb more ca and phosphate.
What does the kidney do for calcium levels?
It converts 25- hydroxycholecalciferol to 1,25 dihydroxycholecalciferol (vitamin D)
Where is cholecalciferol (D3) formed?
Skin
Where is cholecalciferol converted to 25-hydroxycholecalciferol?
liver
The kidneys require what to change 25-hydroxycholecalciferol to 1,25 dihydroxycholecalciferol?
PTH
What is the sequence to forming Vitamin D?
Skin makes cholecalciferol (D3) and liver converts it to 25-hydroxycholecalciferol, which the kidneys convert it to 1,25 dihydroxycholecalciferol (need PTH) for this. This active form of Vitamin D increases absorption of calcium, phosphate.
What is calcitonin?
Peptide hormone secreted by the thyroid gland, it is stimulated by increased plasma calcium concentration.