Marshall J C, Eagleson C A, McCartney C R
Division of Endocrinology/Department of Medicine, Center for Research in Reproduction, University of Virginia Health Sciences Center, PO Box 800612, Charlottesville, VA 22908-0612, USA.
Mol Cell Endocrinol. 2001 Oct 25;183(1-2):29-32. doi: 10.1016/s0303-7207(01)00611-6.
A pulsatile GnRH stimulus is required to maintain gonadotropin synthesis and secretion. The frequency and amplitude of GnRH pulses determine gonadotropin subunit gene expression and secretion of pituitary LH and FSH. Rapid frequency (more than 1 pulse per h) GnRH pulses favor LH while slower frequencies favor FSH secretion. During ovulatory cycles, an increase in GnRH frequency during the follicular phase favors LH synthesis prior to the LH surge, while following ovulation, luteal steroids slow GnRH pulses to favor FSH synthesis. Thus, a changing frequency of GnRH stimulation of the gonadotrope is one of the mechanisms involved in differential gonadotropin secretion during ovulatory cycles. In hypothalamic amenorrhea a majority of women exhibit a persistent slow frequency of LH (GnRH) pulses, which reflects excess hypothalamic opioid tone and can be temporarily reversed by opioid antagonists. At the other end of the spectrum, in polycystic ovarian syndrome, LH (GnRH) pulses are persistently rapid and favor LH synthesis, hyperandrogenism and impaired follicular maturation. Administration of progesterone can slow GnRH pulse secretion, favor FSH secretion and induce follicular maturation. Thus, the ability to change the pattern of GnRH secretion is an important factor in the maintenance of cyclic ovulation, and loss of this function leads to anovulation and amenorrhea.
维持促性腺激素的合成与分泌需要脉冲式GnRH刺激。GnRH脉冲的频率和幅度决定促性腺激素亚基基因的表达以及垂体LH和FSH的分泌。快速频率(每小时超过1次脉冲)的GnRH脉冲有利于LH分泌,而较慢频率则有利于FSH分泌。在排卵周期中,卵泡期GnRH频率增加有利于LH峰之前LH的合成,而排卵后,黄体类固醇使GnRH脉冲减慢以利于FSH合成。因此,对促性腺细胞GnRH刺激频率的改变是排卵周期中促性腺激素分泌差异所涉及的机制之一。在下丘脑性闭经中,大多数女性表现出LH(GnRH)脉冲持续缓慢,这反映了下丘脑阿片样物质张力过高,且可被阿片样物质拮抗剂暂时逆转。在另一个极端,多囊卵巢综合征患者的LH(GnRH)脉冲持续快速,有利于LH合成、高雄激素血症和卵泡成熟受损。给予孕酮可减慢GnRH脉冲分泌,有利于FSH分泌并诱导卵泡成熟。因此,改变GnRH分泌模式的能力是维持周期性排卵的重要因素,而该功能丧失会导致无排卵和闭经。