L 15 pituitary hormones 1 Flashcards
pituitary glands
-the master gland
-hypophysis
-size of a pea
anterior pituitary hormones: growth hormone
-GH
-prolactin
-single chain protein hormones
-activate receptors associated with JAK/STAT pathway
anterior pituitary hormone: thyroid stimulating hormones
-TSH, FSH, LH
-dimeric protein hormones sharing a common alpha chain
-activates GPCRs
anterior pituitary hormones: adrencorticotropic hormones
-ACTH
-single chain peptide
-activiates a GPCR
gonadotropins and human chorionic gonadotropin
-follicle stimulating hormones (FSH)
-luteinizing hormones (LH)
-human chlorionic gonadotropin (hCG)
follicle stimulating hormones (FSH)
-in women: Directs ovarian follicle development and Stimulates the conversion of testosterone to estrogens
-in men: Regulates spermatogenesis and Stimulates the conversion of testosterone to estrogens
luteinizing hormone
in women: Stimulates androgen production in the follicular phase and Controls estrogen and progesterone production in the luteal phase
-in men:Stimulates androgen production
human chorionic gonadotropin
-Produced in the placenta during pregnancy
-Nearly identical with LH (binds LH receptors).
-Controls estrogen and progesterone production during pregnancy
structures of gonadotropins
-FSH, LH, and hCG are all heterodimeric proteins.
Shares the same α-chain.
Distinct β-chain confers receptor specificity.
The β-chains of hCG and LH are nearly identical.
-Administered subcutaneous or intramuscular injection.
-Half-life: 10 – 40 hrs (dependent on the preparation and route of injection
preparations used clinically: menotropins
-Human menopausal gonadotropins (hMG)
-First commercial gonadotropin product
-Extracted from the urine of postmenopausal women.
-Mixture of FSH and LH
-Lower potency than purified FSH or LH.
preparation used clinically: urofollitropin (uFSH)
-FSH purified from the urine of postmenopausal women.
-LH activity is removed during purification
preparations used clinically: follitropin alpha and follitropin beta
-Recombinant forms of FSH
-Identical in amino acid sequence with FSH.
-Differ from each other and uFSH in carbohydrate chains.
-Considerably more expensive than uFSH
preparations used clinically: lutropin alpha
-recombinant form of LH
-Approved for use in combination with follitropin α for stimulation of follicular development in infertile women with LH deficiency.
-Discontinued from US market in 2012
preparations used clinically: hCG
Extracted and purified from the urine of pregnant women
preparations used clinically: choriogonadotropin alpha (rhCG)
recombinant form of hCG
clinical uses -ovulation induction
-in women with anovulation secondary to hypogonadotropic hypogonadism, polycystic ovary syndrome, etc.
High cost
Needs close monitoring during the administration.
Reserved for patients who fail to respond to other treatments (Ex. clomiphene).
-Controlled ovarian hyperstimulation in reproductive technology procedures
-Protocols are based on the physiology of a normal menstrual cycle.
ovulation induction protocol
1)FSH preparations (hMG, uFSH) during the follicular phase.
To prevent premature endogenous surge in LH, the effects of endogenous GnRH need to be blocked by continuous administration of GnRH or GnRH receptor antagonist.
2. Administration of hCG –> ovulation –> insemination or oocyte retrieval
3. Hormonal support during the luteal phase typically by exogenous progesterone.
clinical uses- male infertility
-Most of the symptoms of hypogonadism in men can be treated with exogenous androgens.
-However, treatment of infertility in hypogonadal men requires LH and FSH.
-Protocol
1. Injection of hCG for 8-12 weeks (initial phase)
2. Injection of hMG for months
-Introduction of intracytoplasmic sperm injection (ICSI) reduces significantly the minimum requirement of spermatogenesis.
adverse effects of ovarian hyperstimulation syndrome
-Occurs in 0.5-4% of patients.
-Overproduction of estrogen and progesterone –> vascular hyperpermeability
-Ovarian enlargement, ascites, hydrothorax, and hypovolemia
adverse effects of mulitple pregnancy
15-20% when ovulation induction is used. (1% in general population)
gonadrotropin releasing hormone
-Decapeptide hormone secreted by neurons in the hypothalamus.
-Binds to GPCRs on the plasma membranes of gonadotrope cells in the anterior pituitary.
-Gonadorelin
Acetate salt of synthetic human GnRH
Half-life: 4 mins (intravenous), 3 hrs (subcutaneous)
synthetic analogs of GnRH
-Goserelin, histrelin, leuprolide, nafarelin, triptorelin
-D-amino acid at position 6
-Ethylamide substituted for glycine at position 10 (except nafarelin)
-More potent and longer-lasting than GnRH and gonadorelin
pulsatile secretion of GnRH
-GnRH stimulates the production and release of LH and FSH only when its secretion is pulsatile.
-In the pharmacological use of GnRH and its analog, the pulsatile secretion of GnRH is mimicked.
Intravenous administration of every 1-4 hrs.
-Nonpulsatile administration of GnRH or GnRH analogs inhibits the release of FSH and LH in both women and men, resulting in hypogonadism.
clinical uses stimulation: female infertility
-Injected intravenously in a pulsatile fashion using a portable battery-powered programmable pump.
-Less likely than gonadotropins to cause multiple pregnancies and the ovarian hyperstimulation syndrome.
-Not commonly used due to the inconvenience and cost.
clinical uses stimulation: male infertility
-In men with hypothalamic hypogonadotropic hypogonadism.
-Pulsatile injection using a portable pump (for months).
-Treatment with gonadotropins (hCG and hMG) is more favored.
clinical uses; suppression
-Continuous treatment with a GnRH agonist
- Suppression of gonadotropin release
-Central precocious puberty
Controlled ovarian hyperstimulation: suppression
Suppression of endogenous LH surge that could cause premature ovulation
Daily subcutaneous injection of leuprolide or daily nasal application of nafarelin
endometriosis: suppression
Suppression of gonadotropin releases suppression of ovaries –> reduced production of estrogen and progesterone
prostate cancer: suppression
Combination with an androgen receptor antagonist –> reduction of testosterone levels and effects
GnRH receptor antagonist
-synthetic decapepetides that function as competitive antagonist
-controlled ovarian hyperstimulation (ganirelix, centrorelix)
-advanced prostate cancer
GnRH receptor antagonist: synthetic decapepetides that function as competitive antagonist
-Ganirelix
-Cetrorelix
-Abarelix
-Degarelix
GnRH receptor antagonist: controlled ovarian hyperstimulation
-Produce an immediate antagonist effect –> shorter duration of treatment
-Lower risk of ovarian hyperstimulation syndrome
gonadotropins
-Menotropins
-Urofollitropin
-Follitropin α and follitropin β
-Lutropin α
-hCG
-Choriogonadotropin
GnRH agonist
Gonadorelin
Goserelin
Histrelin
Leuprolide
Nafarelin
Triptorelin
GnRH antagonist
Ganirelix
Cetrorelix
Abarelix
Degarelix
