Pituitary Hormones - 18,19 Flashcards
T or F: there are only 2 portal veins in the body, one for the liver, and one in the anterior pituitary
True
Hypothalamus:Anterior Pituitary hormones
GnRH: ___ and ___
____: ACTH
TRH: ____
___(+) and ___ (-): GH
- LH, FSH
- CRH
- TSH
- GHRH, SST (somatostatin)
Anterior pituitary hormones
growth hormone (GH), prolacatin
* side chain ___ hormones
* activate receptors associated with ___ pathway
- protein
- JAK/STAT
Anterior pituitary hormones
Thyroid stimulating hormone (TSH), FSH, LH
* dimeric protein hormones shaing a common ___ chain
* activate ___
- alpha
- GPCRs
Adrenocorticotropic hormone (ACTH)
- side-chain ___
- activates a ___
- peptide
- GPCR
Growth hormone - Functions
- Mediated primarily via increasing the production of ____ growth factor 1 (IGF-1) in the liver, bone, cartilage, and muscle.
- reduction in ___ sensitivity. Compensated by insulin activity of ___
Defieciency of GH
* failure to reach ___ height
* disproportionately increased body ___
* decreased ___ mass
- insulin-like
- insulin, IGF-1
- adult
- fat
- muscle
What is this?
growth hormone
GH structure
- ___-amino-acid protein with two ___ bonds
- similar to that of ___
- The recombinant form (rhGH, ___) has the identical structure.
- 191, disulfide
- prolactin
- somatotropin
GH metabolism
- Half life: ___ min
- cleared by: ___
- rhGH is administered ___; active blood levels presist for about 36 hrs
- 20-25 minutes
- liver
- subcutaneously
Growth hormone – Clinical uses
Growth hormone deficiency
* acquired or congenital
* ___ due to unopposed action of insulin
- Genetic disorders – Prader-Willi syndrome, ___ syndrome
- Performance enhancer in athletics (banned by IOC)
- Use of recombinant bovine growth hormone (rbGH) in dairy cattle
- Hypoglycemia
- Turner
Mecasermin
- recombinant human IGF-1 (rhIGF-1) used in treatment to severe ___ deficiency (not reponsive to ___ GH. Mutations in GH receptor of develoment of neutralizing antibodies to ___)
- prepared as a complex to maintain ___ (rhIGFBP-3)
- ___ may occur due to the insulin activity of rhIGF-1
- IGF-1, exogenous, GH
- half life
- hypoglycemia
Growth hormone antagonists
GH antagonists are ___ analogs.
* 2 examples of these analogs: ___ and ___
* used to treat ___ and gigantism
* GH receptor antagonist example: ___ : a derivative of a mutant GH. Binds to GH receptor but blocks signal transduction
- somatostatin
- Ocreotide and Lanreotide
- acromegaly
- Pegvisomant (PEG)
acromegaly - abnormal growth of
cartilage, bone, and many other organs
Gonadotropins and human chorionic gonadotropin
Follicle-stimulating hormone (FSH)
* In women: Directs ovarian ___ development. Stimulates the conversion of ___ to estrogens.
* In men: Regulates ___. Stimulates the conversion of testosterone to ___.
- follicle
- testosterone
- spermatigenesis estrogens
Gonadotropins and human chorionic gonadotropin
Luteinizing hormone (LH)
* In women: Stimulates androgen production in the ___ phase.
Controls estrogen and ____ production in the ___ phase.
* In men: Stimulates ___ production.
- follicular, progesterone, luteal
- androgen
Human chorionic gonadotropin (hCG)
* produced in the ___ during pregnancy
* Nearly identical with ___ (binds to its receptors)
* controls estrogen and ___ production during pregnancy
- placenta
- LH
- progesterine
T or F: FSH, LH, and hCG are all heterodimeric proteins.
True
Structures of gonadotropins
- Distinct ___ confers receptor specificity.
- The β-chains of hCG and LH are nearly ___.
Administered ___ or ___ injection.
Half-life: ___ hrs (dependent on the preparation and route of injection)
- β-chain
- identical
- subcutaneous, IM
- 10-40
Menotropins
* Human menopausal gonadotropins - ___
* First commercial gonadotropin product
* Extracted from the urine of ___ women.
* Mixture of FSH and LH
* Lower ___ than purified FSH or LH.
- hMG
- postmenopausal
- potency
Urofollitropin (uFSH)
* ___ purified from the urine of postmenopausal women.
* LH activity is ___during purification.
- FSH
- Removed
Follitropin α and follitropin β
- Recombinant forms of ___
- Identical in ___ sequence with FSH.
- Differ from each other and uFSH in ___ chains.
- Considerably more expensive than ___.
- FSH
- amino acid
- carbohydrate
- uFSH
Lutropin α
* Recombinant form of __
* Approved for use in combination with follitropin α for stimulation of ___ development in infertile women with __ deficiency.
* Discontinued from US market in 2012 because ___ is cheaper
- LH
- follicular, LH
- hCG
hCG
* Extracted and purified from the urine of ___ women.
pregnant
Choriogonadotropin α (rhCG)
* Recombinant form of ___
hCG
Ovulation induction protocol
- FSH preparations (hMG, uFSH) during the follicular phase. To prevent premature endogenous
surge in __, the effects of endogenous GnRH need to be blocked by continuous administration of GnRH or GnRH receptor antagonist. - Administration of ___ → ovulation → insemination or oocyte retrieval.
- Hormonal support during the ___ phase typically by exogenous progesterone.
- LH
- hCG
- luteal
*
Male infertility
- Most of the symptoms of hypogonadism in men can be treated with exogenous ___.
- treatment of infertility in hypogonadal men requires ___ and ___.
1. inject hCG 8-12 weeks
2. inject hMG for months
Introduction of ___ sperm injection (ICSI) reduces significantly the minimum requirement of spermatogenesis.
- androgens
- LH and FSH
- intracytoplasmic
Adverse effects
ovarian ___stimulation syndrome
* overproduction of estrogen and ___ → vascular ___
* Ovarian enlargement, ascites, hydrothorax, and hypovolemia
Multiple ___
* ___% when ovulation induction is used.
- hyperstimulation
- progesterone
- hyperpermeability
- pregnancies
- 15-20%
Gonadotropin-releasing hormone (GnRH)
- ___peptide hormone secreted by the hypothalamus.
- Binds to GPCRs on the plasma membranes of gonadotrope cells in the ___ .
- Gonadorelin -Acetate salt of synthetic human GnRH
- Half-life: ___ (intravenous), ___ (subcutaneous)
- decapeptide
- anterior pituitary
- 4 min, 3 hrs
Synthetic analogs of GnRH
- ___-amino acid at position __
- Ethylamide substituted for ___ at position __ (except nafarelin)
- More potent and longer-lasting than GnRH and ___
- Examples: Goserelin, histrelin, leuprolide, nafarelin, triptorelin
- D, 6
- glycine, 10
- gonadorelin
Pulsatile secretion of GnRH
- GnRH stimulates the production and release of ___ and ___ only when its secretion is ___.
- In the pharmacological use of GnRH and its analog, the pulsatile secretion of GnRH is ___.
- Nonpulsatile administration of GnRH or GnRH analogs ___ the release of FSH and LH in both women and men, resulting in ___.
- LH, FSH, pulsatile
- mimicked
- inhibits, hypogonadism
Clinical uses – Stimulation
Female infertility
* Injected intravenously in a ___ fashion using a portable battery-
powered programmable pump.
* Less likely than ___ to cause multiple pregnancies and ovarian hyperstimulation syndrome.
* Not commonly used due to the inconvenience and ___.
- pulsatile
- gonadotropins
- cost
Clinical uses – Stimulation
Male infertility
* In men with hypothalamic hypogonadotropic hypogonadism.
* ___ injection using a portable pump (for months).
* Treatment with ___ (hCG and hMG) is more favored.
- pulsatile
- gonadotropins
Clinical uses – Suppression
Continuous treatment with a GnRH agonist → ___ of gonadotropin release
suppression
Clinical uses – Suppression
Controlled ovarian hyperstimulation
* Suppression of endogenous ___ surge that could cause premature
ovulation
Daily subcutaneous injection of ___ or daily nasal application of
___
- LH
- leuprolid, nafarelin
Clinical uses – Suppression
Endometriosis
* Suppression of gonadotropin → suppression of ovaries →
reduced production of ___ and ___
estrogen and progesterone
Clinical uses – Suppression
Prostate cancer
* Combination with an androgen receptor ___ → reduction of
___ levels and effects
antagonist, testosterone
GnRH receptor antagonists
Synthetic decapeptides that function as competitive antagonists
* 4 examples
- Ganirelix
- Cetrorelix
- Abarelix
- Degarelix
all end with “relix”
GnRH receptor antagonists used for Controlled ovarian hyperstimulation: ___ and ___
* Produce an ___ antagonist effect
* ___ duration of treatment
* ___ risk of ovarian hyperstimulation syndrome
ganirelix, centrorelix
* immediate
* shorter
* lower
also used for advanced prostate cancer
Prolactin
- ___-amino-acid protein hormone produced in the ___.
- structurally similar to __
- ___ inhibits its secretion
- responsible for lactation
- 198, anterior pituitary
- GH
- dopamine
Prolactin deficiency
* Rare form of ___ abnormality
* no prolactin is available
Hyperprolactinemia
* caused by prolactin secreting ___
* inhibition of ___ release
* ___ and galactorrhea in women; loss of libido and infertility in men
* can be treated with ___ agonist
- pituitary
- adenoma
- GnRH
- amenorrhea
- dopamine
Vasopressin and oxytocin
- ___ pituitary hormones
- Synthesized in neuronal cell bodies in the ___.
- Transported via their ___.
- posterior
- hypothalamus
- axons
Structures of vasopressin and oxytocin
- ___-amino acid peptide hormones with a
ring formed by a ___ bond. - The amino acid sequence of oxytocin is different from that of vasopressin at positions ___ and ___.
- possess some ____activity
Desmopressin
* long acting synthetic analog of ___
* modification at position ___ and __-amino acid at position ___
- 9, disulfide
- 3 and 8
- cross
- vasopressen
- 1, D, 8
Vasopressin
Antidiuretic hormone (ADH); arginine vasopressin (AVP) are released by the posterior pituitary in response to
rising ___ and falling ___
* ___ reabsorption of water from tubular filtrate by increasing water permeability in the cells in renal collecting tubes ( ___ activity)
* ___ in urine volume
* ___ in blood volume
* constricted blood vessels which ___ blood pressure
* Increases the levels of ___ factor and coagulation factor ___.
- plsdms tonicity, blood volume
- increases, antidiuretic
- decrease
- increased
- raised
- Von WIllebrand, VIII
Metabolism and excretion
- Vasopressin (Pitressin) is administered via ___ or ___ injection
- half life ___
- metabolized in the ___ or ___
- reduction of the ___ bond and ___ cleavage
- IM, IV
- 15 min
- liver or kidney
- disulfide bond and peptide
Metabolism and excretion
- Desmopressin (Stimate) is administed ___, ___, intranasally, or orally
- nasal bioavailability ___; oral bioavailability ___
- half life: ___
- IV, subcutaneously
- 3-4%, <1%
- 1.5-2.5 hours
Vasopressin receptors
V1 receptor
* GPCR that increases cytosolic ___ levels upon activation.
* Found on vascular ___ cells.
* mediates ___.
- Ca2+
- smooth muscle
- vasoconstriction
V2 receptor
* GPCR that increases ___ levels
* found on ___ tubule cells
* increased the number of ___ on cellular membrane → ___ water permeability → water resorption
- cAMP
- renal
- aquaporins, increases
Desmopressin has minimal ___ activity; 4000 times higher ___ to ___ activity than vasopressin
* Desmopressin as a nasal spray, as an oral tablet, or by injection
- V1
- antidiuretic, vasopressor
Clinical uses - vasopressin and desmopressin
Pituitary diabetes insipidus
* Deficiency of ___: polyuria, polydipsia, hypernatremia
Bedwetting
Coagulopathy in ___ and von Wilderbrand’s disease
- vasopressin
- hemophilia A
Adverse effects - desmopressin and vasopressin
water intoxification
* Hyponatremia ( low ___)
* Drowsiness, listlessness, headache
fluid intake needs to be ___
* vasopressin (but not desmopressin) should be used with extreme caution in patients with ___ diseases
* ___ cramping
- Na+
- limited
- cardiovascular
- abdominal
Vasopressin antagonists
- Used to treat ___.
- Hyponatremia is frequently associated with acute ___.
- hyponatrmia
- heart failure
Vasopressin antagonists
Conivaptan
* ___ antagonist of V1 and V2 receptors
* administered ___
- non peptide
- IV
Talvaptan
* Selective __
receptor antagonist
* 30 fold higher affinity for ___ vs ___
* administered ___
- V2
- V2, V1
- orally
What is this?
Conivaptan
V1 and V2 antagonist
What is this?
Talvaptan
V2 antagonist
Oxytocin
- Pitocin, Syntocinon
- uterine ___ in labor
- stimulates release of ___ and ___ that lead to uterine contraction
- aids in ___ ejection by contracting myoepithelial cels surrounding ___ alveoli
- acts through a GPCR that increases ___ levels leading to muscle ____
- at high [ ] oxytocin has a weak ___ and vasopressor activity
- social bonding and trust
- contraction
- prostaglandins, leukotrienes
- milk, alveoli
- Ca2+, constriction
- antidiuretic
Clinical uses - oxytocin
- ___ of labor (in the 2nd half of pregnancy, the expression of oxytocin receptors increases in the uterine smooth muscle - positive feedback)
- control uterine ___ after delivery
- enhance ___ ejection (nasal spray)
- induction
- hemorrhage
- milk
Adverse effects - oxytocin
- Excessive stimulation of uterine contraction before delivery (fetal ___, placental ___, uterine ___, birth canal ___)
- Activation of vasopressin receptors by overdose of oxytocin (excessive ___ retention, water ___ , hypo___ )
- distress, abruption, rupture, trauma
- fluid retention
- intoxification
- hyponatremia
