Lecture 15: Pituitary Hormones

Question 1

Anterior pituitary hormones

Answer 1

-gonadotropins
-GnRH

Question 2

Pituitary gland

Answer 2

-master gland
-hypophysis
-size of a pea

Question 3

Anterior pituitary hormones

Answer 3

-grwoth hormone (GH), prolactin
-TSH, FSH, LH
-Adrenocorticotropic hormone (ACTH)

Question 4

GH and prolactin

Answer 4

-single-chain protein hormones
-activate JAK/STAT pathway

Question 5

Thyroid stimulating hormone (TSH), FSH, LH

Answer 5

-dimeric protein hormones
-share common a chain
-activate GPCRs

Question 6

adrentocorticotropic hormone (ACTH)

Answer 6

-single-chain peptide
-activates a GPCR

Question 7

Gonadotropins

Answer 7

-FSH
-LH
-hCG

Question 8

Follicle-stimulating hormone (FSH)

Answer 8

-stimulate conversion of testosterone to estrogens

-ovarian follicle development in women
-regulate spermatogenesis in men

Question 9

Lutenizing hormone (LH)

Answer 9

-stimulates androgen production
-only in follicular phase for women
-controls estrogen and preogesterone production in luteal phase

Question 10

Human chorionic gonadotropin (hCG)

Answer 10

-produced in placenta during pregnancy
-nearly identical with LH (B-chain)
-binds LH receptors
-controls estrogen and progesterone production during pregnancy

Question 11

Gonadotropin structure

Answer 11

-heterodimeric proteins
-common a chain
-distinct B-chain confers specificity
-B-chain of LH and hCG nearly identical
-SC, IM
-10-40 hour half life

Question 12

Gonadotropin clinical products

Answer 12

-menotropins
-urofollitropin (uFSH)
-follitropin a and B
-Lutotropin a
-hCG
-Choriogonadotropin a

Question 13

Menotropins

Answer 13

-human menopausal gonadotropins (hMG)
-1st product
-from urine of postmenopausal women
-FSH and LH but lower potency

Question 14

Urofollitropin (uFSH)

Answer 14

-FSH purified from urine of postmenopausal women
-LH activity removed during purification

Question 15

Follitropin a and Follitropin B

Answer 15

-recombinant FSH forms
-identical amino acid seq to FSH
-differ in carbohydrate chains
-more expensive than uFSH

Question 16

Lutotropin a

Answer 16

-recombinant LH form
-combo with follitropin a for follicular development in women with LH deficiency
-discontinued

Question 17

hCG clinical product

Answer 17

-extracted from urine of pregnant women

Question 18

Choriogonadotropin a (rhCG)

Answer 18

-recombinant hCG

Question 19

Gonadotropic ovulation induction

Answer 19

-in women with anovulation secondary to hypogonadotropic hypogonadism, pcos, etc
-controlled ovarian hyperstimulation in reproductive technology procedures
-protocols based on physiology of normal menstrual cycle
-high cost
-need close monitoring during admin
-reserved for patients who fail other treatments

Question 20

Ovulation induction protocol

Answer 20

1. FSH preparations (hMG, uFSH) during follicular phase
2. admin of hCG = ovulation = insemination or oocyte retrieval
3. hormonal support during luteal phase (exogenous progesterone)

Question 21

How to prevent LH surge in ovulation induction

Answer 21

-endogenous GnRH needs to be blocked by continous admin of GnRH or GnRH antagonist

Question 22

Male infertility treatment protocol

Answer 22

1. injection of hCG for 8-12 weeks (initial phase)
2. injection of hMG for months

Question 23

Use of gonadotropins for male infertility treatment

Answer 23

-LH and FSH
-introduction of intracytoplasmic sperm injection (ICSI) reduces the minimume requirement of spermatogenesis

Question 24

Adverse effects of gonadtropin fertility treatment

Answer 24

-ovarian hyperstimulation syndrome
-multiple pregnancy (15-20%)

Question 25

ovarian hyperstimulation syndrome

Answer 25

-0.5-4%
-overproduction of estrogen and progesterone = vascular hyperpermeability
-ovarian enlargement, ascites, hydrothorax, hypovolemia

Question 26

Gonadotropin-releasing hormone (GnRH)

Answer 26

-decapeptide hormone
-secreted by hypothalmus
-binds GPCR on gonadotrope cells in anterior pituitart
-gonadorelin

Question 27

Gonadorelin

Answer 27

-acetate salt of synthetic GnRH
-4 min IV
-3 hr SC

Question 28

Synthetic analogs of GnRH products

Answer 28

-goserelin
-histrelin
-leuprolide
-nafarelin
-triptorelin

Question 29

synthetic analogs of GnRH features

Answer 29

-D-amino acid at position 6
-ethylamide substituted for glycine at position 10 (except nafarelin)
-more potent
-longer lasting

Question 30

Pulsatile secretion of GnRH

Answer 30

-only way that stimulates LH and FSH release
-IV every 1-4 hr

Question 31

Nonpulsatile admin of GnRH

Answer 31

-INHIBITS release of FSH and LH
=hypogonadism

Question 32

GnRH to treat female infertility

Answer 32

-IV
-pulsatile using portable pump
-less likely to cause multiple pregnancies and hyperstimulation
-inconvienent and expensive

Question 33

GnRH to treat male infertility

Answer 33

-hypothalmic hypogonadism
-PULSATILE IV using pump (months)
-gonadotropin treatment favored

Question 34

GnRH as a suppressant treatment

Answer 34

-ovarian hyperstimulatino
-endometriosis
-prostate cancer
-central precocious puberty

Question 35

continuous GnRH agonist treatment

Answer 35

=suppression of gonadotropin release

Question 36

GnRH treatment of Controlled ovarian hyperstimulation

Answer 36

-suppression of endogenous LH surge that causes premature ovulation
-SC of leuprolide
-nasal application of nafarelin

Question 37

GnRH treatment of endometriosis

Answer 37

-suppress gonadotropin release
=suppress ovaries
=reduce estrogen and progesterone production

Question 38

GnRH treatment of prostate cancer

Answer 38

-combo with androgen agonist
=reduction of testosterone levels and effects

Question 39

GnRH antagonists

Answer 39

-Ganirelix
-Cetrorelix
-Abarelix
-Degarelix

Question 40

use of GnRH ANTAgonists

Answer 40

-ovarian hyperstimulation (shorter duration of treatment)
-advanced prostate cancer