The neuro control of the ovarain cycle – a hypothesis

Abstract

Since more than 100 years, it is known that pituitary function depends upon the function of higher centers in the brain. It was already assumed at this time that pituitary extracts could influence the gonads and postulated that their use could have practical applications. In 1926, the ‘gonadal principle’ was discovered revealing the regulation of ovarian function by the pituitary. The two pituitary hormones were called ‘Prolan A’ and ‘Prolan B’ which are responsible for ovarian function especially secretion of the hormones: ‘lutein’ and ‘foliculin’. If the names of Prolan A and B are changed to follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and the names of foliculin and lutein to estrogen and progesterone, it becomes obvious that the pituitary–gonadal relationship, as we know it today, was first described in 1930. Then, the next step was the isolation, sequence and synthesis of gonadotropin releasing hormone (GnRH) responsible for the secretion of gonadotropins (Gn). It could be shown that GnRH pulse frequency has differential effects on Gn secretion: low-frequency pulses of GnRH stimulate preferentially FSH and high frequency LH secretion. The pulse frequency control depends from a subpopulation of kisspeptin neurons within the infundibular region of the hypothalamus with coexpression of neurokinin B and dynorphin A – KNDy neurons showing a negative feedback to estrogen. A second group of kisspeptide neurons in the rostral periventricular area of the third ventricle is devoid of neurokinin-B and dynorphin, mediates positive feedback from estrogen and so induces the midcycle LH-surge. Therefore, the variability in the frequency and amplitude of GnRH pulsatility is central to the differential regulation of LH and FSH and thus ovarian follicle development, the correct selection of a single dominant follicle for ovulation, the LH surge and the luteal phase.

Chinese abstract

一百多年以来, 众所周知, 垂体功能取决于大脑中的更高级别中心的功能。已经假定, 垂体提取物可以影响性腺, 并假定他们的使用可能具有实际应用。1926年, 性腺原理的发现揭示了脑垂体对卵巢功能的调控。两种垂体激素被称为”Prolan A”和”Prolan B” , 他们是负责卵巢功能, 尤其是”黄体”和”foliculin” 的分泌。如果把Prolan A和Prolan B的名字改为卵泡刺激素（FSH）和黄体生成激素（LH）, foliculin和黄体的名字改为雌激素和孕激素, 很显然就是我们今天所知道的垂体-性腺的关系, 这种关系在1930被第一次描述。然后, 下一步是对促性腺激素释放激素（GnRH）的分离、测序以及合成, GnRH负责促性腺激素（Gn）的分泌。可以看出, GnRH脉冲频率对Gn分泌有不同的影响：低频脉冲的GnRH优先刺激FSH, 而高频脉冲优先刺激LH分泌。脉冲频率控制取决于下丘脑漏斗区内kisspeptin神经元的一个亚群, 和KNDy神经元一起共同表达神经激肽B和强啡肽A, 对雌激素呈现出负反馈的作用。kisspeptin神经元的第二个亚群在第三脑室周围白质区, 缺乏神经激肽B和强啡肽, 介导雌激素正反馈, 从而诱导排卵期LH峰。因此, GnRH的频率和振幅的变化是LH和FSH差异调控的核心, 从而出现了卵巢卵泡的发育, 包括对单个优势卵泡的正确选择, LH峰以及黄体期的形成。

Keywords:

• Cycle function
• pituitary
• GnRH pulsatility
• gonadotropin secretion
• KNDy neurons

Disclosure statement

BL and KB have nothing to declare.