Lecirelin, a synthetic hormone, is a strongly basic nonapeptide with sequence yr-His-Trp-Ser-Tyr-tBu-D-Gly-Leu-Arg-Pro-NHEt. The hormone is also a class of medicine that triggers the rapid secretion of luteinizing hormone (LH) by activating the pituitary gland, leading to ovulation and luteinization. Lecirelin is mainly developed for the treatment of cystic ovarian disease.
Follicular cysts (FC) are an important ovarian disorder associated with abnormal estrous behaviour and infertility. The main reason for the occurrence of FC is that low levels of progesterone inhibit the sensitivity of the hypothalamus to estradiol, causing the lower part of the thalamus to lose the ability to respond to elevated estradiol levels. The pituitary gland can not secrete LH, causing follicles not to ovulate, which results in ovarian follicular cysts. Cyst follicles have the ability to respond to LH, therefore the treatment of FC is injections of lecirelin to trigger the release of LH from the pituitary. LH can promote the ovulation of mature follicles and the luteinization of cyst follicles. Then the luteinized cysts are dissolved by PGF2a or its analogue for the purpose of cure.
Lecirelin has been registered as a veterinary drug Supergestran. The drug is intended for the induction of ovulation in livestock at the time of insemination, as well as for therapy of cystic ovarian disease and improvement of conception rates. For example, lecirelin is used for synchronization of oestrus and timing of ovulation in cows and buffalo. In addition, lecirelin is widely used to control follicular dynamics and ovulation in fixed timed insemination protocols at present.
Pharmacokinetics and metabolism
Lecirelin injected into the body is widely distributed in the extracellular fluid. The metabolism of lecirelin is completed by enzymatic degradation and renal excretion. Lecirelin is mainly cleared by the kidneys. In vitro perfusion experiment showed that lecirelin can be filtered by the glomerulus, degraded by the proximal renal tubule, but cannot be reabsorbed by the renal tubule. The lecirelin's liver metabolism is negligible because of its low intake and excretion. However, the net blood flow of the liver, muscle and skin is extremely large, so these organs are still of significance for the metabolic clearance rate of lecirelin. The main metabolites of lecirelin are the products produced by the lysis of pyroglutamyl aminopeptidase and neutral endopeptidase.
1. Sázelová P, Kašička V, Šolínová V, et al. Determination of purity degree and counter-ion content in lecirelin by capillary zone electrophoresis and capillary isotachophoresis[J]. Journal of Chromatography B, 2006, 841(1):145-151.
2. Picard-Hagen N, Lhermie G, Florentin S, et al. Effect of gonadorelin, lecirelin, and buserelin on LH surge, ovulation, and progesterone in cattle[J]. Theriogenology, 2015, 84(2):177-183.
3. Rizzo A, Annalisa R, Campanile D, et al. Epidural vs intramuscular administration of lecirelin, a GnRH analogue, for the resolution of follicular cysts in dairy cows.[J]. Animal Reproduction Science, 2011, 126(1-2):19-22.
4. Awan F S, Mehmood M U, Sattar A, et al. Comparative efficacy of hCG or GnRH analogue (lecirelin acetate) on follicular dynamics, degree of endometrial edema, sexual behavior, ovulation and pregnancy rate in crossbred broodmares[J]. Journal of Equine Veterinary Science, 2016, 41:71-72.