Luteinizing Hormone-Releasing Hormone (LHRH) and Analogs
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Introduction
Luteinizing hormone-releasing hormone (LHRH), also known as Gonadotropin-releasing hormone (GnRH), is known for its role as the final common signaling molecule by stimulating the synthesis of LH and FSH to regulate reproductive behaviors in all vertebrates. Synthesized in the hypothalamus, LHRH primarily acts on the gonadotrophs in the pituitary gland, which expresses a recognized member of the G-protein coupled, Ca2+-dependent receptor. It also secretes Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH), which together, play a crucial role during puberty to allow both the male and female body to reach sexual maturity which eventually leads to the fertility.
Mechanism of action
The receptors of LHRH are found in breast tumors and pituitary gland in the brain. Moreover, neural plasma membrane is also found to contain specific binding site for LHRH. The mechanism by which LHRH binds to membrane before it binds to the receptors is a very critical step and can have a profound impact upon the translation of peptide across the membrane. A complex form of glycosphingolipids known as Ganglioside is an important component of plasma membrane of nerve cells and breast tumor tissues. They play an important role in various physiological membrane processes. Therefore, the interaction of ganglioside-containing membrane with LHRH might be crucial in aiding the LHRH to translate through the neural membrane and reach its receptor for binding and activation.
Application of Luteinizing Hormone-Releasing Hormones (LHRH) and Analogs
Cytotoxic analogs of LHRH (luteinizing hormone-releasing hormone) can be successfully used for the treatment of hormone-dependent cancers such as prostatic, ovarian, endometrial. Long-term administration of luteinizing hormone-releasing hormone analogs (LHRHa) is the main type of androgen-deprivation therapy (ADT) for lethal prostate cancer. In patients with advanced prostate cancer, LHRH agonists have been shown to achieve improvements in survival, progression-related outcomes, and time-to-treatment failure that are similar to bilateral orchiectomy, a procedure that many patients find psychologically difficult to accept.
References
- Meani D., Solarić M., Visapää H., Rosén RM., Janknegt R., &Soče M. (2017). Practical differences between luteinizing hormone-releasing hormone agonists in prostate cancer: perspectives across the spectrum of care. Ther Adv Urol,10(2):51-63.
- Oláh G., Dobos N., Vámosi G., Szabó Z., Sipos É., Fodor K., Harda K., Schally AV.,& Halmos G. (2018). Experimental therapy of doxorubicin resistant human uveal melanoma with targeted cytotoxic luteinizing hormone-releasing hormone analog (AN-152). Eur J Pharm Sci, 123:371-376.
- Zarrin Shahzadi., Chaitali Mukhopadhyay. (2017). Interaction Between Luteinizing Hormone-Releasing Hormone and GM1-Doped Cholesterol/Sphingomyelin Vesicles: A Spectroscopic Study. The Journal of Membrane Biology, 250(6), 617-627.
