Term
| what is central to endocrine physiology? |
|
Definition
| the hypothalamus-pituitary-target organ axis |
|
|
Term
| what is the role of the peptides from the hypothalamus? |
|
Definition
| stimulate or inhibit the pituitary |
|
|
Term
| what is the role of the pituitary? |
|
Definition
| releases a number of trophic hormones that stimulate targets to produce their own hormones |
|
|
Term
| what happens to endogenous secretion of hormones in a patient receiving exogenous hormones? |
|
Definition
| negative feedback shuts off endogenous secretion of trophic hormones and shuts off secretion |
|
|
Term
| products of the pituitary gland are what type of hormones? |
|
Definition
| ALL products are peptide hormones |
|
|
Term
| what are the products of the pituitary? |
|
Definition
| GH, ACTH, TSH, FSH, LH, prolactin |
|
|
Term
| what governs release of hormones from the pituitary? |
|
Definition
| specific releasing hormones from the hypothalamus |
|
|
Term
| the majority of products of the target organs are what type of hormones? |
|
Definition
|
|
Term
| examples of peptide hormones? |
|
Definition
GH, FSH - from pituitary
insulin - from B cells of pancreas
calcitonin - from C cells of the thyroid gland
somatostatin - made all over the body |
|
|
Term
| what are the 2 main structural classes of hormones? |
|
Definition
| peptide and steroid hormones |
|
|
Term
| difference in plasma half life between peptide and steroid hormones? |
|
Definition
peptide - short
steroid - long |
|
|
Term
| why does the plasma half life differ between steroid and peptide hormones? |
|
Definition
| peptides are not bound to carrier proteins but steroids extensively bind increasing their plasma half lives |
|
|
Term
| what class of hormones are water soluble? |
|
Definition
| peptides - they are hydrophilic and unable to cross the membrane |
|
|
Term
| what class of hormones are fat soluble? |
|
Definition
| steroid hormones - they are lipophilic and can easily cross the membranes to enter cells |
|
|
Term
| how do peptides exert their effect? |
|
Definition
| activate cell surface receptors which turns on many different pathways in the cell |
|
|
Term
| onset and offset of peptide hormones in a cell? |
|
Definition
|
|
Term
| how do steroid hormones exert their effect in the cell? |
|
Definition
| activate intracellular receptors that act in the nucleus |
|
|
Term
| onset of steroid hormones action? |
|
Definition
| slow onset and offset in the cells because they increase the transcription of certain genes |
|
|
Term
| which class of hormones are orally active? |
|
Definition
|
|
Term
| are peptide hormones orally active? |
|
Definition
NO
have to be given subQ or IM or intranasally (calcitonin) |
|
|
Term
| examples of steroid hormones? |
|
Definition
estradiol
testosterone
vitamin D
thyroid hormones |
|
|
Term
| what are the hormones of the anterior pituitary (6)? |
|
Definition
1. GH
2. prolactin
3. thyrotropin
4. FSH
5. LH
6. adrenocorticotropin |
|
|
Term
| what 2 anterior pituitary hormones are single chain amino acids? |
|
Definition
1. GH - used as a drug often
2. prolactin - secretion is regulated by drugs |
|
|
Term
what 3 anterior pituitary hormones are 2 chains?
which chain is most important and why? |
|
Definition
TSH, FSH, LH
beta is more important than alpha because it confers specificity and Ab are made against it |
|
|
Term
| ACTH is secreted from what type of cells? |
|
Definition
|
|
Term
| ACTH is derived from what? |
|
Definition
|
|
Term
| GH is also known as what? |
|
Definition
| somatotropin or somatropin |
|
|
Term
| GH is secreted from what? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
positive regulation - GHRH
negative regulation - somatostatin
both secreted by the hypothalamus |
|
|
Term
|
Definition
| in a pattern - increased 1 hour after sleep onset and stress |
|
|
Term
|
Definition
| stimulates IGF-1 production mainly from the liver |
|
|
Term
| what is responsible for many of the actions of GH? |
|
Definition
| the production of IGF1 which is longer acting |
|
|
Term
| GH or IGF1 effects increased in the body? |
|
Definition
1. stimulate cartilage and skeletal growth
2. protein synthesis
3. increase in muscle mass |
|
|
Term
|
Definition
potent anti-insulin activity - leads to decreased glucose utilization and hyperglycemia and increased lipolysis
main effects - break down fat and increase muscle |
|
|
Term
| GH receptor is coupled to what? |
|
Definition
| Janus Kinase (JAK) tyrosine kinase receptor activating STAT transcription factors |
|
|
Term
| clinical uses of recombinant human GH (6)? |
|
Definition
anywhere with reduced muscle mass
1. poor growth due to GH deficiency
2. Turner's syndrome
3. chronic kidney disease
4. idiopathic short stature
5. muscle wasting from HIV
6. burn patients |
|
|
Term
| recombinant human growth hormone administration? |
|
Definition
| injected subcutaneously up to 6 times per week |
|
|
Term
| recombinant human growth hormone side effects? |
|
Definition
1. hyperglycemia, glucosuria
2. gynecomastia
3. fluid retention - swollen hands and feel
4. intracranial HTN |
|
|
Term
| what is the mechanism of gynecomastia as a side effect of therapy with recombinant human growth hormone? |
|
Definition
| GH activates prolactin receptors |
|
|
Term
| what is sermorelin acetate? |
|
Definition
synthetic form of GHRH
only the first 29 amino acids of GHRH but has the full activity |
|
|
Term
| why is sermorelin acetate better than GH? |
|
Definition
| it is less expensive than GH and is well tolerated |
|
|
Term
| what is required for treatment with sermorelin acetate? |
|
Definition
| requires functional somatotrophs to release GH |
|
|
Term
| when is sermorelin acetate used? |
|
Definition
| when there is a problem with the release of GH |
|
|
Term
| effect of prolactin in the body? |
|
Definition
| mammary development and lactation |
|
|
Term
| when do prolactin levels increase in the body? |
|
Definition
| with sleep, stress, pregnancy, and suckling there are natural increases |
|
|
Term
| what is the positive control of prolactin? |
|
Definition
|
|
Term
| what is the predominant control of prolactin? |
|
Definition
| predominantly negative control by dopamine |
|
|
Term
| is prolactin used pharmacologically? |
|
Definition
|
|
Term
| why is hyperprolactinemia important? |
|
Definition
| it is one of the leading causes of infertility and amenorrhea in women |
|
|
Term
| what are the 5 classes of causes of hyperprolactinemia? |
|
Definition
1. neurogenic - suckling, nipple stimulation
2. hypothalamic and interruption of portal circulation
3. pituitary - prolactin secreting tumors, etc
4. endocrine - pregnancy, estrogen admin (birth control)
5. drugs impairing DA secretion and action |
|
|
Term
| how can drug interactions cause hyperprolactinemia? |
|
Definition
drugs that affect DA storage or DA antangonists --> impact ability of DA to inhibit prolactin secretion --> increase prolaction --> phenothiazines, sulpiride, metoclopramide, haloperidol
or any drug that depletes DA at the terminals - methyldopa, cimietidine |
|
|
Term
a 12 year old boy with diagnosed GH deficiency is treated with recombinant GH. the plasma level of what peptide is a sensitive measure of treatment efficacy?
a. anti-diuretic hormone (ADH)
b. prostaglandin E2
c. insulin-like growth factor 1
d. thyrotropin releasing hormone (TRH) |
|
Definition
| c. insulin-like growth factor 1 |
|
|
Term
| a test for athletes abusing the use of GH as a performance enhancing agent would test for what? |
|
Definition
|
|
Term
if insulin-like growth factor 1 is administered to an individual, plasma levels of GH will likely:
a. increase
b. stay the same
c. decrease |
|
Definition
c. decrease
classic negative feedback - exogenous product shuts down endogenous production |
|
|
Term
| what is the main regulator of prolactin secretion? |
|
Definition
| negative regulation by DA |
|
|
Term
| why can't hyperprolactinemia be treated with just DA? |
|
Definition
| DA is a catecholamine with a short half life that isn't orally active - it would have to be infused 24 hrs/day |
|
|
Term
| what is the prototype ergot alkaloid with D2 receptor activity? |
|
Definition
|
|
Term
| bromocriptine is what type of drug? |
|
Definition
| ergot alkaloid DA agonist |
|
|
Term
| what 2 drugs are used to treat hyperprolactinemia? |
|
Definition
1. bromocriptine
2. ergonovine |
|
|
Term
| how does ergonovine differ from bromocriptine? |
|
Definition
|
|
Term
does bromocriptine:
cause uterine stimulation?
act on serotonin receptors?
act on DA receptors?
act on a-adrenergic receptors? |
|
Definition
NO
NO
stimulates D2 receptors
weak antagonist |
|
|
Term
| bromocriptine action at a-adrenergic receptors? |
|
Definition
|
|
Term
|
Definition
*1. hyperprolactinemia and amenorrhea
2. reduces size of prolactin-secreting tumors prior to surgery
3. stop milk production after abortion, miscarriage, or medical reason to stop breast feeding
4. acromegaly (excess GH) due to pituitary adenoma
5. reduces the symptoms of PD
6. improves glucose control in type 2 DM by increasing post-prandial insulin secretion |
|
|
Term
|
Definition
| relative selective agonist of DA type 2 receptors on mammotrophs |
|
|
Term
| bromocriptine side effects? |
|
Definition
1. nausea
2. vomiting
*3. postural hypotension
*4. mental disturbances |
|
|
Term
| what is the mechanism of postural hypotension as a side effect of bromocriptine? |
|
Definition
| due to its activity as an a-adrenergic antagonist |
|
|
Term
| what is the mechanism of mental disturbances as a side effect of bromocriptine? |
|
Definition
| because it can cross the BBB - especially in the elderly |
|
|
Term
| how can bromocriptine be altered to increase it efficacy? |
|
Definition
| can be long acting or given as a vaginal suppository |
|
|
Term
| what is a more selective D2 receptor agonist than bromocriptine and why is it better? |
|
Definition
cabergoline
has less side effects |
|
|
Term
| what drug is a somatostatin analog? |
|
Definition
|
|
Term
| what is the role of somatostatin in the pituitary? |
|
Definition
| inhibits the release of GH and TSH |
|
|
Term
| where is somatostatin found? |
|
Definition
| all over the body - especially in the GI tract |
|
|
Term
| what type of hormone is somatostatin? |
|
Definition
|
|
Term
| the majority of the functions of somatostatin are what type? |
|
Definition
| inhibitory of hormone secretion or GI actions |
|
|
Term
| what hormones are inhibited by somatostatin in the pituitary gland? |
|
Definition
|
|
Term
| what hormones are inhibited by somatostatin in the GI tract? |
|
Definition
| gastrin, secretin, gastrointestinal polypeptide, motilin, glicentin, VIP |
|
|
Term
| what hormones are inhibited by somatostatin in the pancreas? |
|
Definition
| insulin, glucagon, somatostatin |
|
|
Term
| what hormones are inhibited by somatostatin in the genitourinary tract? |
|
Definition
|
|
Term
| besides hormone secretion, what is the function of somatostatin in the GI tract? |
|
Definition
| inhibits other actions like gastric acid secretion, emptying, absorption, etc |
|
|
Term
| what is a long acting somatostatin analog? |
|
Definition
|
|
Term
| how is octreotide administered for short term use? |
|
Definition
| 3 times a day subcutaneously |
|
|
Term
| how is octreotide administered for long term use? |
|
Definition
| in depot form for IM injections every 2-3 months |
|
|
Term
| why is octreotide better than somatostatin? |
|
Definition
| much longer acting drug that mimics the effects of somatostatin |
|
|
Term
| how does the half life of octreotide compare to somatostatin? |
|
Definition
much longer
somatostatin - 2-3 mins
octreotide - 2-3 hours |
|
|
Term
| side effects of octreotide (5)? |
|
Definition
1. constipation
2. redness at injection site
3. hypothyroidism
4. sinus bradycardia
5. changes in blood sugar |
|
|
Term
| what is the mechanism of hypothyroidism as a side effect of octreotide? |
|
Definition
| it inhibits TSH secretion |
|
|
Term
|
Definition
1. acromegaly and pituitary tumors secreting TSH
2. GI issues
3. neuroendocrine tumors
3. treatment of diarrhea associated with a number of different GI problems
4. postural hypotension
5. migraine, psoriasis |
|
|
Term
| what hormone from the hypothalamus stimulates FSH release in both men and women? |
|
Definition
|
|
Term
| importance of FSH or LH in men and women? |
|
Definition
FSH in women - important for estrogen production
LH in men - activates leydig cells in the testes to make testosterone |
|
|
Term
| how is GnRH release for optimal functioning? |
|
Definition
released in a pulsatile fashion from the hypothalamus - about once every 30-60 mins
this maintains the receptor on gonadotrophs at the optimal level |
|
|
Term
| what is essential for maintaining physiological health of the hormonal axis of the gonads? |
|
Definition
| pulsatile secretion of GnRH |
|
|
Term
| how are short acting analogs of GnRH given and how do they function? |
|
Definition
given exactly the same as endogenous GnRH (as a pulse)
results in the normal physiological function |
|
|
Term
| uses of short acting analogs of GnRH? |
|
Definition
| treatment of hypogonadism, delayed puberty, cryptorchidism, and diagnostic |
|
|
Term
| half life of short acting analogs of GnRH? |
|
Definition
|
|
Term
| administration of short acting analogs of GnRH? |
|
Definition
| used in mini-pump SC or IV in short, intermittent pulses |
|
|
Term
| 2 long acting analogs of GnRH? |
|
Definition
1. leuprolide - prototype
2. goserelin |
|
|
Term
| uses of long acting analogs of GnRH? |
|
Definition
*1. prostate cancer
2. breast cancer
3. endometriosis
4. suppression of FSH and LH in fertility induction protocols |
|
|
Term
| what drug type causes 'chemical castration'? |
|
Definition
| long acting analogs of GnRH |
|
|
Term
| how does the activity of long acting analogs of GnRH compare to naural GnRH? |
|
Definition
| long acting analogs of GnRH are 25x more potent |
|
|
Term
| half life of long acting analogs of GnRH? |
|
Definition
| 3 hours - much longer than GnRH |
|
|
Term
| long acting analogs of GnRH administration? |
|
Definition
| available in depot form, injection IM every month to every 3 months |
|
|
Term
| effect of long acting analogs of GnRH on FSH and LH secretion? |
|
Definition
initial increase
then suppression |
|
|
Term
| side effects of long acting analogs of GnRH? |
|
Definition
1. hot flashes
2. loss of libido
3. decrease in bone mass
4. vaginal dryness
5. initial disease flare due to testosterone (or estradiol in women) surge |
|
|
Term
|
Definition
|
|
Term
| administration of GnRH antagonists? |
|
Definition
|
|
Term
| side effects of GnRH antagonist degarelix? |
|
Definition
| same as for long acting analogs of GnRH except NO initial disease flare and NO immediate hypersensitivity reactions seen with other GnRH antagonists |
|
|
Term
| why don't GnRH antagonists cause an initial disease flare? |
|
Definition
| they don't down regulate the receptors |
|
|
Term
| what do most GnRH antagonists cause? |
|
Definition
| an immediate hypersensitivity reaction and increased histamine release |
|
|
Term
| what are 4 ways to treat prostate cancer? |
|
Definition
1. GnRH antagonists - degarelix
2. long acting analog of GnRH - leuprolide
3. negative feedback with high dose exogenous estrogen
4. androgen receptor antagonist |
|
|
Term
| how do high doses of exogenous estrogen treat prostate cancer? |
|
Definition
| negative feedback shuts off production of LH and FSH |
|
|
Term
| 2 androgen receptor antagonists used in the treatment of prostate cancer? |
|
Definition
1. flutamide
2. bicalutamide |
|
|
Term
| how are androgen receptor antagonists used in the treatment of prostate cancer? |
|
Definition
| used in combo with GnRH analogs to block effects of testosterone during initial flare up or added later when there is a break through of PSA levels |
|
|
Term
| side effects of androgen receptor antagonists? |
|
Definition
|
|
