Introduction
Gonadorelin is a synthetic GnRH, a peptide compound, and a decapeptide whose structure is exactly the same as the natural extract of gonadorelin secreted by the hypothalamus of mammals. Gonadorelin stimulates the anterior pituitary to secrete follicular hormone (FSH) and luteinizing hormone (LH), which together promote female ovulation and is thus used to treat infertility caused by hypothalamus amenorrhea.
Pharmacologic action
The study found that GnRH levels in human body plays a vital role in human development. Too much of it will lead to early puberty in children, and too little will lead to infertility. Usually, GnRH is secreted by the hypothalamus, but many women with infertility cannot ovulate normally due to insufficient hypothalamus secretion. In the process of action of gonadotropin on pituitary-gonadotropin cells, a typical G protein coupled receptor and specific binding of protein produce inositol triphosphate (IP3) and diacylglycerol (DG), which work with Ca2+ to activate phospholipase C (PKC). The activated PKC activates the expression of receptor genes in the nucleus through two ways, thus promoting the release of LH and FSH.
Function
Clomiphene, also a GnRH, is used to treat infertility drugs. It can activate the hypothalamus when the dosage is low and promote ovulation successfully, but when the dosage is increased, there will be obvious antagonism. So clomiphene doesn't work for all patients. Unlike Clomiphene and other GnRH analogues, Gonadorelin is not used to suppress sex hormone production. Some patients who do not respond to clomiphene can be treated with Gonadorelin. As early as 1978, Gonadorelin was available for medical use.. And now, it is available throughout the world for clinical treatment including the United States, Canada, Australia, Japan, and in many other countries.
Pharmacokinetics and metabolism
In the study of intravenous injection of Gonadorelin, the blood concentration reached the peak after 3 minutes of injection and excreted after rapid metabolism of the kidney. The effect of Gonadorelin on LH in plasma was fast and strong, while the effect on FSH was slow and weak. After intravenous injection, the initial phase of t1/2 was 2-10 min, the final phase was 10-40 min, and the action time was 3-5 h. Gonadorelin is quickly metabolized into an inactive segment in plasma, which is excreted through urine without residual problems.
References:
1. Robert Grosse, et al. Gonadotropin -releasing hormone receptor initiates multiple signaling pathways by exclusively coupling to Gq/ 11 proteins. The Journal of Biological Chemistry. 2000, 275(13):9193 -9200
2. Nachum Reiss, et al. Mechanism of mitogen -activated protein kinase activation by gonadot ropin -releasing hormone in the pituitary α T3 -1 cell line: Diferenti al roles of calcium and protein kinase c. Endocrinology .1997 , 138(4):1673 -1682
