Lecture 15: Pituitary Hormones Flashcards
Anterior pituitary hormones
-gonadotropins
-GnRH
Pituitary gland
-master gland
-hypophysis
-size of a pea
Anterior pituitary hormones
-grwoth hormone (GH), prolactin
-TSH, FSH, LH
-Adrenocorticotropic hormone (ACTH)
GH and prolactin
-single-chain protein hormones
-activate JAK/STAT pathway
Thyroid stimulating hormone (TSH), FSH, LH
-dimeric protein hormones
-share common a chain
-activate GPCRs
adrentocorticotropic hormone (ACTH)
-single-chain peptide
-activates a GPCR
Gonadotropins
-FSH
-LH
-hCG
Follicle-stimulating hormone (FSH)
-stimulate conversion of testosterone to estrogens
-ovarian follicle development in women
-regulate spermatogenesis in men
Lutenizing hormone (LH)
-stimulates androgen production
-only in follicular phase for women
-controls estrogen and preogesterone production in luteal phase
Human chorionic gonadotropin (hCG)
-produced in placenta during pregnancy
-nearly identical with LH (B-chain)
-binds LH receptors
-controls estrogen and progesterone production during pregnancy
Gonadotropin structure
-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
Gonadotropin clinical products
-menotropins
-urofollitropin (uFSH)
-follitropin a and B
-Lutotropin a
-hCG
-Choriogonadotropin a
Menotropins
-human menopausal gonadotropins (hMG)
-1st product
-from urine of postmenopausal women
-FSH and LH but lower potency
Urofollitropin (uFSH)
-FSH purified from urine of postmenopausal women
-LH activity removed during purification
Follitropin a and Follitropin B
-recombinant FSH forms
-identical amino acid seq to FSH
-differ in carbohydrate chains
-more expensive than uFSH
Lutotropin a
-recombinant LH form
-combo with follitropin a for follicular development in women with LH deficiency
-discontinued
hCG clinical product
-extracted from urine of pregnant women
Choriogonadotropin a (rhCG)
-recombinant hCG
Gonadotropic ovulation induction
-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
Ovulation induction protocol
- FSH preparations (hMG, uFSH) during follicular phase
- admin of hCG = ovulation = insemination or oocyte retrieval
- hormonal support during luteal phase (exogenous progesterone)
How to prevent LH surge in ovulation induction
-endogenous GnRH needs to be blocked by continous admin of GnRH or GnRH antagonist
Male infertility treatment protocol
- injection of hCG for 8-12 weeks (initial phase)
- injection of hMG for months
Use of gonadotropins for male infertility treatment
-LH and FSH
-introduction of intracytoplasmic sperm injection (ICSI) reduces the minimume requirement of spermatogenesis
Adverse effects of gonadtropin fertility treatment
-ovarian hyperstimulation syndrome
-multiple pregnancy (15-20%)
ovarian hyperstimulation syndrome
-0.5-4%
-overproduction of estrogen and progesterone = vascular hyperpermeability
-ovarian enlargement, ascites, hydrothorax, hypovolemia
Gonadotropin-releasing hormone (GnRH)
-decapeptide hormone
-secreted by hypothalmus
-binds GPCR on gonadotrope cells in anterior pituitart
-gonadorelin
Gonadorelin
-acetate salt of synthetic GnRH
-4 min IV
-3 hr SC
Synthetic analogs of GnRH products
-goserelin
-histrelin
-leuprolide
-nafarelin
-triptorelin
synthetic analogs of GnRH features
-D-amino acid at position 6
-ethylamide substituted for glycine at position 10 (except nafarelin)
-more potent
-longer lasting
Pulsatile secretion of GnRH
-only way that stimulates LH and FSH release
-IV every 1-4 hr
Nonpulsatile admin of GnRH
-INHIBITS release of FSH and LH
=hypogonadism
GnRH to treat female infertility
-IV
-pulsatile using portable pump
-less likely to cause multiple pregnancies and hyperstimulation
-inconvienent and expensive
GnRH to treat male infertility
-hypothalmic hypogonadism
-PULSATILE IV using pump (months)
-gonadotropin treatment favored
GnRH as a suppressant treatment
-ovarian hyperstimulatino
-endometriosis
-prostate cancer
-central precocious puberty
continuous GnRH agonist treatment
=suppression of gonadotropin release
GnRH treatment of Controlled ovarian hyperstimulation
-suppression of endogenous LH surge that causes premature ovulation
-SC of leuprolide
-nasal application of nafarelin
GnRH treatment of endometriosis
-suppress gonadotropin release
=suppress ovaries
=reduce estrogen and progesterone production
GnRH treatment of prostate cancer
-combo with androgen agonist
=reduction of testosterone levels and effects
GnRH antagonists
-Ganirelix
-Cetrorelix
-Abarelix
-Degarelix
use of GnRH ANTAgonists
-ovarian hyperstimulation (shorter duration of treatment)
-advanced prostate cancer
