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编号: | 200226 |
中文名称: | 黄体生成素释放激素LHRH (1-2) (free acid) |
英文名: | LHRH (1-2) (free acid) |
CAS号: | 32159-22-1 |
单字母: | Pyr-H-OH |
三字母: | Pyr 焦谷氨酸(Glp、pGlu、Pyr)是一种在蛋白质N端位置发现的蛋白质生成氨基酸。它是由N端谷氨酸残基环化形成内酰胺而产生的。 -HisL-组氨酸:histidine。系统命名为(2S)-氨基-3-(4-咪唑基)丙酸。其侧链带有弱碱性的咪唑基,为编码氨基酸。是幼小哺乳动物的必需氨基酸。符号:H,His。 -OHC端羧基:C-terminal carboxyl group。在肽或多肽链中含有游离羧基的氨基酸一端。在表示氨基酸序列时,通常将C端放在肽链的右边。 |
氨基酸个数: | 1 |
分子式: | C11H14N4O4 |
平均分子量: | 266.25 |
精确分子量: | 266.1 |
等电点(PI): | - |
pH=7.0时的净电荷数: | 0.24 |
平均亲水性: | -0.5 |
疏水性值: | -3.2 |
消光系数: | - |
来源: | 人工化学合成,仅限科学研究使用,不得用于人体。 |
储存条件: | 负80℃至负20℃ |
标签: | 促黄体生成激素释放激素(LHRH) 组氨酸类 垂体和下丘脑激素 |
The GnRH II sequence pEHWSHGWYPG amide, first detected in chicken, is highly conserved in vertebrates.
Definition
Luteinizing hormone-releasing hormone (LHRH), also known as Gonadotropin-Releasing Hormone (GnRH) or Luteinizing Hormone-Releasing Factor (LRF) is a hypothalamic neuropeptide which acts on the pituitary to stimulate the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
Discovery
LHRH was first characterized by the groups of two Nobel Laureates Guillemin and Schally in 1977. The hypophysiotropic form of the peptide is part of a larger family of decapeptides and was the first to be discovered and characterized in mammals. The discovery of multiple LHRHs in mammalian and non-mammalian species across a wide evolutionary taxa [over 20 LHRHs identified to date] has resulted in a nomenclature based on the species each of the LHRHs was first discovered 1.
Structural Characteristics
LHRH is translated from the mRNA as a pro-hormone, which is subsequently converted to the mature decapeptide (pGlu-His- Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) in secretory vesicles prior to its release 2. Subsequent to its secretion, LHRH may be further cleaved by soluble peptidases for the purposes of degrading, converting, or transforming 3.
Mode of Action
The effects of LHRH are mediated by high-affinity G protein-coupled LHRH-receptor (LHRH-R) on pituitary gonadotropes. In humans and most vertebrates, there are two forms of LHRHs, LHRH-I and LHRH-II that exist in the brain and in peripheral tissues. Furthermore, the processed peptide of LHRH-I, LHRH-(1–5), appears also to have biological activities that are in contrast to its parent activities. Enormous interest has been focused on LHRH-I and LHRH-II and their cognate receptors as targets for designing therapies to treat cancers of the reproductive system. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth and sixth bond of the decapeptide (Tyr5-Gly6) to form LHRH-(1–5). Autoregulation of LHRH gene expression can also be mediated by its processed peptide, LHRH-(1–5). LHRH-(1–5) may act through one of the alternative LHRH receptors, such as the LHRH-RII. This is plausible since LHRH-(1–5) share the first 4 amino acids with at least 9 LHRH-I forms. LHRH-(1–5) have contrasting effects from its parent peptide, LHRH-I, could help explain the lack of correlation between the action of LHRH-I analogs that behave as antagonists at the pituitary level but result in agonist-like anti-proliferative effects in many cancers 4, ,5.
Functions
As growth modulatory factor: LHRH may act as a growth modulatory factor in tumors of the reproductive system. LHRH and LHRH receptors (LHRH-Rs) are expressed in human melanoma cells and LHRH-Rs are found in greater than 50% of human breast cancers 6.
Action on ovary: LHRH is released in pulses and triggers the production of gonadotropins, which stimulate the growth and release of eggs by the ovary. This fact has been best illustrated by experiments in which the actions of the decapeptide have been blocked by immunoneutralization or receptor antagonist treatment, which invariably leads to cessation or reduction of gonadotropin secretion, disruption of gonadal function, and infertility. Sterility in mutant, non-LHRH-producing mice and human infertility associated with LHRH insufficiency also provide a clear demonstration of the reproductive consequences of inappropriate or deficient LHRH neurosecretion 6. In the rat, administration of an LHRH antagonist during proestrus results in a rapid and complete inhibition of ovulation, demonstrating the importance of this neuropeptide in reproductive function.
Hypothalamic anovulation: In women, a disorder called hypothalamic anovulation occurs when the hypothalamus does not produce LHRH, which in turn results in a lack of egg production and release by the ovaries. Similarly, if the LHRH secretion pattern is altered by prolonged stressful situations, a female will show symptoms of dysmenorrhea or amenorrhea, while a male will exhibit alteration of steroidogenesis as well as spermatogenesis.
Reproductive maturation: Regulation of the synthesis and secretion of hypothalamic LHRH neurons plays a fundamental role in the process of reproductive maturation in both mammalian genders. Indeed, an increase in pulsatile LHRH release is the critical factor for the onset of puberty; hypothalamic LHRH content shows a steady increase during the first three months of life in male rats, and an increase in pulsatile LHRH release occurs at the onset of puberty in female rhesus monkeys.
References
1. Walters K, Wegorzewska IN, Chin YP, Parikh MG, Wu TJ (2008). Luteinizing Hormone-Releasing Hormone I (LHRH-I) and Its Metabolite in Peripheral Tissues. Experimental Biology and Medicine, 233 (2):123-130.
2. Wetsel WC, Mellon PL, Weiner RI, Negro-Vilar A (1991). Metabolism of pro-luteinizing hormone-releasing hormone in immortalized hypothalamic neurons. Endocrinology, 129:1584-1595.
3. Wu TJ, Mani SK, Glucksman MJ, Roberts JL (2005). Stimulation of luteinizing hormone-releasing hormone (LHRH) gene expression in GT1–7 cells by its metabolite, LHRH-(1–5). Endocrinology, 146:280–286.
4. Ramakrishnappa N, Rajamahendran R, Lin Y-M, Leung PCK (2005). GnRH in non-hypothalamic reproductive tissues. Anim Reprod Sci., 88:95-113.
5. Swanson TA, Kim SI, Myers M, Pabon A, Philibert KD, Wang M, Glucksman MJ. The role of neuropeptide processing enzymes in endocrine (prostate) cancer: EC 3.4.24.15 (EP24.15). Protein Pept Lett., 11:471-478.
6. Bajo AM, Schally AV, Halmos G, Nagy A (2003). Targeted Doxorubicin-containing Luteinizing Hormone-releasing Hormone Analogue AN-152 Inhibits the Growth of Doxorubicin-resistant MX-1 Human Breast Cancers. Clinical Cancer Research, 9: 3742-3748.
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