Department of Investigative Medicine, Imperial College, London, UK.
Adv Exp Med Biol. 2013;784:63-87. doi: 10.1007/978-1-4614-6199-9_4.
The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which is cleaved into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter reviews in detail the effects of kisspeptin on gonadotropin secretion in non-human mammals. Studies of kisspeptin's effects have included both acute and chronic administration regimens via a number of administration routes. Acute kisspeptin stimulates gonadotropin secretion in a wide range of species of non-human mammals, including rats, mice, hamsters, sheep, pigs, goats, cows, horses, and monkeys. In general, the stimulatory effect of kisspeptin treatment is more pronounced for LH than FSH secretion. Kisspeptin is thought to exert its stimulatory effects on LH and FSH release via stimulation of GnRH release from the hypothalamus, since pre--administration of a GnRH antagonist prevents kisspeptin's stimulation of gonadotropin secretion. Although the kisspeptin receptor is also expressed on anterior pituitary cells of some species, and incubation of anterior pituitary cells with high concentrations of kisspeptin can stimulate in vitro LH release, the contribution of direct effects of kisspeptin on the pituitary is thought to be negligible in vivo. Continuous kisspeptin administration results in reduced sensitivity to the effects of kisspeptin, in some species. This desensitization is thought to occur at the level of the kisspeptin receptor, since the response of the pituitary gland to exogenous GnRH is maintained. Overall, the findings discussed in this chapter are invaluable to the understanding of the reproductive role of kisspeptin and the potential therapeutic uses of kisspeptin for the treatment of fertility disorders.
Kiss1 基因编码一个 145 个氨基酸的前肽，即 kisspeptin，它被切割成 54、14、13 和 10 个氨基酸的更小肽。本章详细回顾了 kisspeptin 对非人类哺乳动物促性腺激素分泌的影响。 kisspeptin 作用的研究包括通过多种给药途径进行的急性和慢性给药方案。急性 kisspeptin 刺激包括大鼠、小鼠、仓鼠、绵羊、猪、山羊、牛、马和猴子在内的多种非人类哺乳动物的促性腺激素分泌。一般来说，kisspeptin 处理对 LH 的刺激作用比 FSH 分泌更为明显。 kisspeptin 被认为通过刺激下丘脑 GnRH 的释放来发挥其对 LH 和 FSH 释放的刺激作用，因为 GnRH 拮抗剂的预先给药可防止 kisspeptin 对促性腺激素分泌的刺激。尽管 kisspeptin 受体也在一些物种的垂体前叶细胞上表达，并且用高浓度 kisspeptin 孵育垂体前叶细胞可以刺激体外 LH 释放，但 kisspeptin 对垂体的直接作用的贡献被认为在体内可以忽略不计。在一些物种中，持续给予 kisspeptin 会导致对 kisspeptin 作用的敏感性降低。这种脱敏被认为发生在 kisspeptin 受体水平，因为外源性 GnRH 对垂体的反应得以维持。总的来说，本章讨论的研究结果对于理解 kisspeptin 在生殖中的作用以及 kisspeptin 治疗生育障碍的潜在治疗用途是非常有价值的。
