Pituitary Hormones - 18,19

Question 1

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

Answer 1

True

Question 2

Hypothalamus:Anterior Pituitary hormones

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

Answer 2

• LH, FSH
• CRH
• TSH
• GHRH, SST (somatostatin)

Question 3

Anterior pituitary hormones

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

Answer 3

• protein
• JAK/STAT

Question 4

Anterior pituitary hormones

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

Answer 4

• alpha
• GPCRs

Question 5

Adrenocorticotropic hormone (ACTH)

• side-chain ___
• activates a ___

Answer 5

• peptide
• GPCR

Question 6

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

Answer 6

• insulin-like
• insulin, IGF-1
• adult
• fat
• muscle

Question 7

What is this?

Answer 7

growth hormone

Question 8

GH structure

• ___-amino-acid protein with two ___ bonds
• similar to that of ___
• The recombinant form (rhGH, ___) has the identical structure.

Answer 8

• 191, disulfide
• prolactin
• somatotropin

Question 9

GH metabolism

• Half life: ___ min
• cleared by: ___
• rhGH is administered ___; active blood levels presist for about 36 hrs

Answer 9

• 20-25 minutes
• liver
• subcutaneously

Question 10

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

Answer 10

• Hypoglycemia
• Turner

Question 11

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

Answer 11

• IGF-1, exogenous, GH
• half life
• hypoglycemia

Question 12

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

Answer 12

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

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

Question 13

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 ___.

Answer 13

• follicle
• testosterone
• spermatigenesis estrogens

Question 14

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.

Answer 14

• follicular, progesterone, luteal
• androgen

Question 15

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

Answer 15

• placenta
• LH
• progesterine

Question 16

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

Answer 16

True

Question 17

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)

Answer 17

• β-chain
• identical
• subcutaneous, IM
• 10-40

Question 18

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.

Answer 18

• hMG
• postmenopausal
• potency

Question 19

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

Answer 19

• FSH
• Removed

Question 20

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 ___.

Answer 20

• FSH
• amino acid
• carbohydrate
• uFSH

Question 21

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

Answer 21

• LH
• follicular, LH
• hCG

Question 22

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

Answer 22

pregnant

Question 23

Choriogonadotropin α (rhCG)
* Recombinant form of ___

Answer 23

hCG

Question 24

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.

Answer 24

• LH
• hCG
• luteal
  *

Question 25

# 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.

Answer 25

* androgens * LH and FSH * intracytoplasmic

Question 26

# Adverse effects ovarian ___stimulation syndrome * overproduction of estrogen and ___ → vascular ___ * Ovarian enlargement, ascites, hydrothorax, and hypovolemia Multiple ___ * ___% when ovulation induction is used.

Answer 26

* hyperstimulation * progesterone * hyperpermeability * pregnancies * 15-20%

Question 27

# 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)

Answer 27

* decapeptide * anterior pituitary * 4 min, 3 hrs

Question 28

# 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

Answer 28

* D, 6 * glycine, 10 * gonadorelin

Question 29

# 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 ___.

Answer 29

* LH, FSH, pulsatile * mimicked * inhibits, hypogonadism

Question 30

# 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 ___.

Answer 30

* pulsatile * gonadotropins * cost

Question 31

# 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.

Answer 31

* pulsatile * gonadotropins

Question 32

# Clinical uses – Suppression Continuous treatment with a GnRH agonist → ___ of gonadotropin release

Answer 32

suppression

Question 33

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

Answer 33

* LH * leuprolid, nafarelin

Question 34

# Clinical uses – Suppression Endometriosis * Suppression of gonadotropin → suppression of ovaries → reduced production of ___ and ___

Answer 34

estrogen and progesterone

Question 35

# Clinical uses – Suppression Prostate cancer * Combination with an androgen receptor ___ → reduction of ___ levels and effects

Answer 35

antagonist, testosterone

Question 36

# GnRH receptor antagonists Synthetic decapeptides that function as competitive antagonists * 4 examples

Answer 36

* Ganirelix * Cetrorelix * Abarelix * Degarelix | all end with "relix"

Question 37

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

Answer 37

ganirelix, centrorelix * immediate * shorter * lower | also used for advanced prostate cancer

Question 38

# Prolactin * ___-amino-acid protein hormone produced in the ___. * structurally similar to __ * ___ inhibits its secretion * responsible for lactation

Answer 38

* 198, anterior pituitary * GH * dopamine

Question 39

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

Answer 39

* pituitary * adenoma * GnRH * amenorrhea * dopamine

Question 40

# Vasopressin and oxytocin * ___ pituitary hormones * Synthesized in neuronal cell bodies in the ___. * Transported via their ___.

Answer 40

* posterior * hypothalamus * axons

Question 41

# 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 ___

Answer 41

* 9, disulfide * 3 and 8 * cross * vasopressen * 1, D, 8

Question 42

# 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 ___.

Answer 42

* plsdms tonicity, blood volume * increases, antidiuretic * decrease * increased * raised * Von WIllebrand, VIII

Question 43

# Metabolism and excretion * Vasopressin (Pitressin) is administered via ___ or ___ injection * half life ___ * metabolized in the ___ or ___ * reduction of the ___ bond and ___ cleavage

Answer 43

* IM, IV * 15 min * liver or kidney * disulfide bond and peptide

Question 44

# Metabolism and excretion * Desmopressin (Stimate) is administed ___, ___, intranasally, or orally * nasal bioavailability ___; oral bioavailability ___ * half life: ___

Answer 44

* IV, subcutaneously * 3-4%, <1% * 1.5-2.5 hours

Question 45

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

Answer 45

* Ca2+ * smooth muscle * vasoconstriction

Question 46

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

Answer 46

* cAMP * renal * aquaporins, increases

Question 47

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

Answer 47

* V1 * antidiuretic, vasopressor

Question 48

# Clinical uses - vasopressin and desmopressin Pituitary diabetes insipidus * Deficiency of ___: polyuria, polydipsia, hypernatremia Bedwetting Coagulopathy in ___ and von Wilderbrand’s disease

Answer 48

* vasopressin * hemophilia A

Question 49

# 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

Answer 49

* Na+ * limited * cardiovascular * abdominal

Question 50

# Vasopressin antagonists * Used to treat ___. * Hyponatremia is frequently associated with acute ___.

Answer 50

* hyponatrmia * heart failure

Question 51

# Vasopressin antagonists Conivaptan * ___ antagonist of V1 and V2 receptors * administered ___

Answer 51

* non peptide * IV

Question 52

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

Answer 52

* V2 * V2, V1 * orally

Question 53

What is this?

Answer 53

Conivaptan | V1 and V2 antagonist

Question 54

What is this?

Answer 54

Talvaptan | V2 antagonist

Question 55

# 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

Answer 55

* contraction * prostaglandins, leukotrienes * milk, alveoli * Ca2+, constriction * antidiuretic

Question 56

# 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)

Answer 56

* induction * hemorrhage * milk

Question 57

# 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___ )

Answer 57

* distress, abruption, rupture, trauma * fluid retention * intoxification * hyponatremia