Function of Gonadorelin Acetate in Central Precocious Puberty
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Function of Gonadorelin Acetate in Central Precocious Puberty

2018-09-21

Introduction 

Gonadorelin acetate, a synthetic decapeptide with sequence Glp-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, is a gonadotropin-releasing hormone (GnRH), which is synthesized and secreted from GnRH neurons within the hypothalamus. GnRH analogues are generally considered to be very safe drugs and have been extensively applied in all sorts of clinical applications, especially reproductive medicine. Among them, gonadorelin acetate has been proved to be very effective in the treatment of central precocious puberty (CPP) in children.

Pharmacologic action

CPP, the essence of which is GnRH-dependent precocious puberty, is caused by the increasing secretion and release of GnRH in advance by the hypothalamus leading to premature reactivation of the gonadotropic axis along with progressive pubertal development, accelerated growth rate and advancement of skeletal age. It is much more common in girls than boys. The treatment target of CPP is usually to reduce the secretion and release of GnRH. Gonadorelin acetate competitively binds to the GnRH receptor of gonadotropin cells in the anterior pituitary, to induce a transient increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the initial treatment, resulting in desensitization and down-regulation of GnRH receptors and a suppression of LH, FSH, and GnRH with the continuous administration of gonadorelin acetate later.

Function

Gonadorelin acetate, as one of the GnRH agonist analogues, possesses plenty of applications in reproductive medicine. It is well recognized that the LH-RH stimulation test with gonadorelin acetate test is the gold standard for diagnosis of CPP. Meanwhile gonadorelin acetate can be seen as an effective drug for the treatment of CPP. In addition to the above, gonadorelin acetate has also been developed as a good choice for the treatment of cryptorchism, as well as the diagnosis of the hypothalamic-pituitary-gonadal axis function.

Pharmacokinetics and metabolism

Gonadorelin acetate is usually injected into body by intravenous administration. After the injection of gonadorelin acetate, there are a distribution half-life of 2 to 10 minutes and a very short terminal half-life of 10 to 40 minutes. Gonadorelin acetate works for 3 to 5 hours and then is rapidly metabolized into inactive peptide components by hydrolysis in plasma and excreted in urine.

References:

1. Akın O, Yavuz S T, Hacıhamdioğlu B, et al. Anaphylaxis to gonadorelin acetate in a girl with central precocious puberty[J]. Journal of Pediatric Endocrinology & Metabolism, 2015, 28(11-12):1387-1389.

2. Chirico V, Lacquaniti A, Salpietro V, et al. Central precocious puberty: from physiopathological mechanisms to treatment[J]. International Journal of Immunopathology & Pharmacology, 2014, 28(27):367-375.

3. Kaplowitz P B. Treatment of central precocious puberty[J]. Curr Opin Endocrinol Diabetes Obes, 2009, 15(5):31-36.

4. Heger S, Partsch C J, Sippell W G. Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function[J]. Journal of Clinical Endocrinology & Metabolism, 1999, 84(12):4583-4590.

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