The neuro control of the ovarain cycle - a hypothesis.

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.