Figure 7:

Schematic illustration of the positive feedback effects of E₂. The current concept shown in (A) is that an increase in E₂ from ovarian follicles during the late follicular phase gives a signal to interneurons expressing estrogen receptor (ER) α, such as kisspeptin neurons, in the hypothalamus, which stimulates perikarya and neuroterminals of GnRH neurons resulting in GnRH surge and subsequent LH surge from the pituitary. However, the results of a recent study indicate that the current concept is insufficient, as the removal of locally synthesized E₂ (neuroestradiol) in the median eminence by the aromatase inhibitor, letrozole, reduces the amount of GnRH and LH. Therefore, we will need to revise the concept (B): An increase in E₂ from the ovary stimulates not only the interneurons such as kisspeptin neurons, but also cells that locally synthesize E₂ (neuroestradiol), which stimulates GnRH neurons directly or indirectly resulting in a full GnRH and LH surge (B). From Kenealy et al., 2017. Permission pending.