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PHRM 825 > Pituitary Hormones - 18,19 > Flashcards

Pituitary Hormones - 18,19 Flashcards

1
Q

T or F: there are only 2 portal veins in the body, one for the liver, and one in the anterior pituitary

A

True

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2
Q

Hypothalamus:Anterior Pituitary hormones

GnRH: ___ and ___
____: ACTH
TRH: ____
___(+) and ___ (-): GH

A
  • LH, FSH
  • CRH
  • TSH
  • GHRH, SST (somatostatin)
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3
Q

Anterior pituitary hormones

growth hormone (GH), prolacatin
* side chain ___ hormones
* activate receptors associated with ___ pathway

A
  • protein
  • JAK/STAT
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4
Q

Anterior pituitary hormones

Thyroid stimulating hormone (TSH), FSH, LH
* dimeric protein hormones shaing a common ___ chain
* activate ___

A
  • alpha
  • GPCRs
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5
Q

Adrenocorticotropic hormone (ACTH)

  • side-chain ___
  • activates a ___
A
  • peptide
  • GPCR
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6
Q

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

A
  • insulin-like
  • insulin, IGF-1
  • adult
  • fat
  • muscle
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7
Q

What is this?

A

growth hormone

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8
Q

GH structure

  • ___-amino-acid protein with two ___ bonds
  • similar to that of ___
  • The recombinant form (rhGH, ___) has the identical structure.
A
  • 191, disulfide
  • prolactin
  • somatotropin
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9
Q

GH metabolism

  • Half life: ___ min
  • cleared by: ___
  • rhGH is administered ___; active blood levels presist for about 36 hrs
A
  • 20-25 minutes
  • liver
  • subcutaneously
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10
Q

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
A
  • Hypoglycemia
  • Turner
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11
Q

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
A
  • IGF-1, exogenous, GH
  • half life
  • hypoglycemia
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12
Q

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

A
  • somatostatin
  • Ocreotide and Lanreotide
  • acromegaly
  • Pegvisomant (PEG)

acromegaly - abnormal growth of
cartilage, bone, and many other organs

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13
Q

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 ___.

A
  • follicle
  • testosterone
  • spermatigenesis estrogens
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14
Q

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.

A
  • follicular, progesterone, luteal
  • androgen
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15
Q

Human chorionic gonadotropin (hCG)
* produced in the ___ during pregnancy
* Nearly identical with ___ (binds to its receptors)
* controls estrogen and ___ production during pregnancy

A
  • placenta
  • LH
  • progesterine
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16
Q

T or F: FSH, LH, and hCG are all heterodimeric proteins.

A

True

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17
Q

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)

A
  • β-chain
  • identical
  • subcutaneous, IM
  • 10-40
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18
Q

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.

A
  • hMG
  • postmenopausal
  • potency
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19
Q

Urofollitropin (uFSH)
* ___ purified from the urine of postmenopausal women.
* LH activity is ___during purification.

A
  • FSH
  • Removed
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20
Q

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 ___.
A
  • FSH
  • amino acid
  • carbohydrate
  • uFSH
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21
Q

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

A
  • LH
  • follicular, LH
  • hCG
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22
Q

hCG
* Extracted and purified from the urine of ___ women.

A

pregnant

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23
Q

Choriogonadotropin α (rhCG)
* Recombinant form of ___

A

hCG

24
Q

Ovulation induction protocol

  1. 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.
  2. Administration of ___ → ovulation → insemination or oocyte retrieval.
  3. Hormonal support during the ___ phase typically by exogenous progesterone.
A
  • LH
  • hCG
  • luteal
    *
25
Q

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.

A
  • androgens
  • LH and FSH
  • intracytoplasmic
26
Q

Adverse effects

ovarian ___stimulation syndrome
* overproduction of estrogen and ___ → vascular ___
* Ovarian enlargement, ascites, hydrothorax, and hypovolemia

Multiple ___
* ___% when ovulation induction is used.

A
  • hyperstimulation
  • progesterone
  • hyperpermeability
  • pregnancies
  • 15-20%
27
Q

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)
A
  • decapeptide
  • anterior pituitary
  • 4 min, 3 hrs
28
Q

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
A
  • D, 6
  • glycine, 10
  • gonadorelin
29
Q

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 ___.
A
  • LH, FSH, pulsatile
  • mimicked
  • inhibits, hypogonadism
30
Q

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 ___.

A
  • pulsatile
  • gonadotropins
  • cost
31
Q

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.

A
  • pulsatile
  • gonadotropins
32
Q

Clinical uses – Suppression

Continuous treatment with a GnRH agonist → ___ of gonadotropin release

A

suppression

33
Q

Clinical uses – Suppression

Controlled ovarian hyperstimulation
* Suppression of endogenous ___ surge that could cause premature
ovulation
Daily subcutaneous injection of ___ or daily nasal application of
___

A
  • LH
  • leuprolid, nafarelin
34
Q

Clinical uses – Suppression

Endometriosis
* Suppression of gonadotropin → suppression of ovaries →
reduced production of ___ and ___

A

estrogen and progesterone

35
Q

Clinical uses – Suppression

Prostate cancer
* Combination with an androgen receptor ___ → reduction of
___ levels and effects

A

antagonist, testosterone

36
Q

GnRH receptor antagonists

Synthetic decapeptides that function as competitive antagonists
* 4 examples

A
  • Ganirelix
  • Cetrorelix
  • Abarelix
  • Degarelix

all end with “relix”

37
Q

GnRH receptor antagonists used for Controlled ovarian hyperstimulation: ___ and ___
* Produce an ___ antagonist effect
* ___ duration of treatment
* ___ risk of ovarian hyperstimulation syndrome

A

ganirelix, centrorelix
* immediate
* shorter
* lower

also used for advanced prostate cancer

38
Q

Prolactin

  • ___-amino-acid protein hormone produced in the ___.
  • structurally similar to __
  • ___ inhibits its secretion
  • responsible for lactation
A
  • 198, anterior pituitary
  • GH
  • dopamine
39
Q

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

A
  • pituitary
  • adenoma
  • GnRH
  • amenorrhea
  • dopamine
40
Q

Vasopressin and oxytocin

  • ___ pituitary hormones
  • Synthesized in neuronal cell bodies in the ___.
  • Transported via their ___.
A
  • posterior
  • hypothalamus
  • axons
41
Q

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 ___

A
  • 9, disulfide
  • 3 and 8
  • cross
  • vasopressen
  • 1, D, 8
42
Q

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 ___.

A
  • plsdms tonicity, blood volume
  • increases, antidiuretic
  • decrease
  • increased
  • raised
  • Von WIllebrand, VIII
43
Q

Metabolism and excretion

  • Vasopressin (Pitressin) is administered via ___ or ___ injection
  • half life ___
  • metabolized in the ___ or ___
  • reduction of the ___ bond and ___ cleavage
A
  • IM, IV
  • 15 min
  • liver or kidney
  • disulfide bond and peptide
44
Q

Metabolism and excretion

  • Desmopressin (Stimate) is administed ___, ___, intranasally, or orally
  • nasal bioavailability ___; oral bioavailability ___
  • half life: ___
A
  • IV, subcutaneously
  • 3-4%, <1%
  • 1.5-2.5 hours
45
Q

Vasopressin receptors

V1 receptor
* GPCR that increases cytosolic ___ levels upon activation.
* Found on vascular ___ cells.
* mediates ___.

A
  • Ca2+
  • smooth muscle
  • vasoconstriction
46
Q

V2 receptor
* GPCR that increases ___ levels
* found on ___ tubule cells
* increased the number of ___ on cellular membrane → ___ water permeability → water resorption

A
  • cAMP
  • renal
  • aquaporins, increases
47
Q

Desmopressin has minimal ___ activity; 4000 times higher ___ to ___ activity than vasopressin
* Desmopressin as a nasal spray, as an oral tablet, or by injection

A
  • V1
  • antidiuretic, vasopressor
48
Q

Clinical uses - vasopressin and desmopressin

Pituitary diabetes insipidus
* Deficiency of ___: polyuria, polydipsia, hypernatremia

Bedwetting

Coagulopathy in ___ and von Wilderbrand’s disease

A
  • vasopressin
  • hemophilia A
49
Q

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

A
  • Na+
  • limited
  • cardiovascular
  • abdominal
50
Q

Vasopressin antagonists

  • Used to treat ___.
  • Hyponatremia is frequently associated with acute ___.
A
  • hyponatrmia
  • heart failure
51
Q

Vasopressin antagonists

Conivaptan
* ___ antagonist of V1 and V2 receptors
* administered ___

A
  • non peptide
  • IV
52
Q

Talvaptan
* Selective __
receptor antagonist
* 30 fold higher affinity for ___ vs ___
* administered ___

A
  • V2
  • V2, V1
  • orally
53
Q

What is this?

A

Conivaptan

V1 and V2 antagonist

54
Q

What is this?

A

Talvaptan

V2 antagonist

55
Q

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
A
  • contraction
  • prostaglandins, leukotrienes
  • milk, alveoli
  • Ca2+, constriction
  • antidiuretic
56
Q

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)
A
  • induction
  • hemorrhage
  • milk
57
Q

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___ )
A
  • distress, abruption, rupture, trauma
  • fluid retention
  • intoxification
  • hyponatremia

PHRM 825 (49 decks)

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