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25 Cards in this Set
- Front
- Back
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hypothalamic-pituitary-gonadal axis |
-hypothalamus releases Gonadotrophin releasing hormone (GnRH) -GnRH acts on the anterior pituitary to release Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) -LH and FSH act on Gonads to secrete the sex steroids (androgens, estrogens, progesterone) -sex steroids negatively feed back on hypothalamus and anterior pituitary *note the pre-ovulatory surge of estrogen actually has a stimulatory effect on GnRH and Gn production |
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gonadotropins |
follicle-stimulating hormone (FSH) luteinizing hormone (LH) Chorionic gonadotropin (CG) |
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what is chorionic gonadotropin |
a gonadotropin -produced by fertilized ovum, then by placenta in pregnancy -sequence similar to LH, interacts with LH receptors in both men and women |
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FSH action in females
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-stimulates the growth of the developing ovarian follicles during the first half of the menstrual cycle -promotes the synthesis of estrogen (LH is also required) |
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LH action in females |
-induces ovulation -stimulates progesterone and estrogen synthesis by the corpus luteum (formed from the remaining cells of the ruptured follicle) during the second half of the menstrual cycle |
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CG action in females |
acts to maintain the corpus luteum when ovum is fertilized |
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LH action in males |
stimulates the synthesis of testosterone by the Leydig cells of the testes |
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FSH action in males |
promotes spermatogenesis (testosterone is also required) |
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CG action in males |
not produced -exogenous CG acts like LH |
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diagnostic uses of gonadotropins |
1. pregnancy testing -CG levels in maternal blood and urine 2. prediction of ovulation -ovulation occurs ~36h after onset of LH surge and 10-12h after peak 3. to assist in determining cause of impaired sex hormone production -primary gonadal failure: ovaries or testes fail to respond to stimulation by gonadotropins -secondary gonadal failure: failure of hypothalamus to secrete GnRH or pituitary to secrete gonadotropins (this is also known as hypogonadotrophic hypogonadism) |
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therapeutic uses of gonadotropins |
treatment of infertility in both men and women -usually hypogonadotrophic hypogonadism |
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side effects in women who use gonadotropins to treat infertility |
-multiple births -ovarian hyperstimulation syndrome (massive ovarian enlargement, fluid accumulation leading to abdominal pain, renal failure) |
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gonadotropin preparations |
originally obtained from human urine -menotropins: roughly equal amounts of FSH and LH -urofollitropin: FSH only -chorionic gonadotropin recombinant versions of FSH, LH and CG now available |
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endometriosis |
-presence of fxnal endometrial tissue outside the uterine cavity -development and growth are estrogen-dependent; implants produce prostaglandins (contribute to pain and inflammation) -may result in chronic pain, as well as infertility |
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pharmacological approaches to treat endometriosis |
-involve disrupting the normal hormonal environment, including producing a hypoestrogenic state by interfering with gonadotropin produciton |
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GnRH |
-decapeptide -very short half-life (2-4 min) -necessary for pulsitile action |
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GnRH agonist/antagonist |
-both GnRH agonists and GnRH antagonists now available -both groups of drugs are analogues of GnRH with changes to aa sequence that alters their activity -both used in situations where we want to decrease release of Gn and sex steroids |
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how do GnRH agonists work? |
-have increased affinity for GnRH receptor on pituitary gland - more potent -less susceptible to proteolysis - longer duration -results in down-regulation of GnRH receptors on pituitary gland (agonist phase at beginning of tx) |
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uses of GnRH agonists |
in conditions in which we want to suppress Gn and sex steroid secretion: -endometriosis -advanced prostate cancer -precocious puberty -uterine fibroids -hyperandrogenism in women |
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GnRH antagonists |
-analogues of GnRH that are competitive reversible antagonists of GnRH at its receptor on pituitary cells -induce a rapid, reversible inhibition of LH and FSH secretion, with no agonist phase at beginning of tx -ADRs appear to be similar to GnRH agonists (result of decreased steroid production) |
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GnRH analogue uses |
used to investigate delayed puberty and tx of infertility in both men and women |
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example of GnRH analogue |
Gonadorelin acetate |
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examples of GnRH agonists |
Buserelin Leuprolide Nafarelin |
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examples of GnRH antagonist |
Ganirelix |
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uses of GnRH antagonists |
approved to prevent premature LH surge and ovulation in in vitro fertilization cycles for use in advanced prostate cancer |
