GnRH receptor

Initial evidence for such patching and uptake was provided by Hopkins and Gre- 

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Hypogonadotropic hypogonadism Gonadotropin-releasing hormone (GnRH) receptor GnRH peptidomimetic antagonist... 

The genetic defects for two of the more common X-linked subtypes of IHH, congenital IHH with anosmia (or Kalhnann syndrome, KS), and IHH with adrenal insufficiency (adrenal hypoplasia congenita) are distinct from the forms of the disease caused by GnRH receptor (GnRHR) mutations. These forms of IHH are included for the sake of clarity. 

GnRH itself has a short half-life, 7 minutes, if given intravenously. Structural variations of the decapeptide have resulted in more stable analogues with higher affinity for the GnRH receptor a common modification is to substitute a D-amino acid for the sixth amino acid, glycine, in GnRH. 

Four synthetic decapeptides that function as competitive antagonists of GnRH receptors are available for clinical use. Ganirelix, cetrorelix, abarelix, and degarelix inhibit the secretion of FSH and LH in a dose-dependent manner. Ganirelix and cetrorelix are approved for use in controlled ovarian hyperstimulation procedures, whereas abarelix and degarelix are approved for men with advanced prostate cancer. 

Leuprolide Agonist of GnRH receptors Increased LH and FSH secretion with intermittent administration reduced LH and FSH secretion with prolonged continuous administration Ovarian suppression, controlled ovarian hyperstimulation, central precocious puberty advanced prostate cancer Administered IV, SC, IM or intranasally depot formulations are available Toxicity Headache, lightheadedness, nausea, injection site reactions t symptoms of hypogonadism with continuous treatment... 

Ganirelix Blocks GnRH receptors Reduces endogenous production of LH and FSH Prevention of premature LH surges during controlled ovulation hyperstimulation SC injection Toxicity Nausea, headache... 

Control of androgen secretion and activity and some sites of action of antiandrogens (1), competitive inhibition of GnRH receptors (2), stimulation (+, pulsatile administration) or inhibition via desensitization of GnRH receptors (-, continuous administration) (3), decreased synthesis of testosterone in the testis (4), decreased synthesis of dihydrotestosterone by inhibition of 5a-reductase (5), competition for binding to cytosol androgen receptors. 

In one case, a complex cyst, thought to be due to ovarian hyperstimulation, resolved after monthly administration of a depot gonadorelin (GnRH) receptor agonist without abandoning tamoxifen (72). One might expect some patients to react to tamoxifen with ovarian hyperstimulation, since another non-steroidal antiestrogen (that is clomiphene) is used for ovarian stimulation and also on occasion produces cysts. 

Cetrorelix is a synthetic decapeptide that reversibly binds to pituitary GnRH receptors without activating them. Cetrorelix thus inhibits the secretion of FSH and LH in a dose-dependent manner by competing with natural hypothalamic GnRH for pituitary cell surface receptors. At the doses used for in vitro fertilization, cetrorelix produces an immediate suppression of LH this delays the LH surge and thus delays ovulation. At higher doses, cetrorelix also suppresses FSH secretion, thus inhibiting the secretion of estradiol from the ovaries. 

Although the GnRH receptor contains a conserved Asn in TM1, this TM1 residue was not included in Weinstein s study. 

Bookstaff RC, Kamel F, Moore RW, et al. 1990b. Altered regulation of pituitary gonadotropin-releasing hormone (GnRH) receptor number and pituitary responsiveness to GnRH in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats. Toxicol Appl Pharmacol 105 78-92. 

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