Chronic estradiol exposure suppresses LH surge without affecting kisspeptin neurons and ERα in anteroventral periventricular nucleus

Yuyu Kunimura
Kinuyo Iwata
Hirotaka Ishii
Hitoshi Ozawa

Abstract Mammalian ovulation is induced by a luteinizing hormone (LH) surge
 which is triggered by elevated plasma estrogen levels; however
 chronic exposure to high levels of estradiol (E2) is known to inhibit LH secretion. In the present study
 we hypothesized that the inhibition of the LH surge by chronic E2 exposure is due to the downregulation of the estrogen receptor α (ERα) in kisspeptin neurons at the hypothalamic anteroventral periventricular nucleus (AVPV)
 which is known as the gonadotropin-releasing hormone (GnRH)/LH surge generator. Animals exposed to E2 for 2?days showed an LH surge
 whereas those exposed for 14?days showed a significant suppression of LH. Chronic E2 exposure did not affect the number of AVPV kisspeptin neurons and the percentage of kisspeptin neurons with ERα or c-Fos
 but did affect the number of kisspeptin neurons in the arcuate nucleus (ARC). Furthermore
 chronic E2 exposure did not affect GnRH neurons. In the pituitary
 14-day E2 exposure significantly reduced the expression of Lhb mRNA and LHβ-immunoreactive areas. GnRH-induced LH release was also reduced significantly by 14-day E2 exposure. We revealed that the suppression of an LH surge by chronic E2 exposure was induced in association with the significant reduction in kisspeptin neurons in the ARC
 LH expression in the pituitary
 and pituitary responsiveness to GnRH
 and was not caused by changes in the ERα-expressing kisspeptin neurons in the AVPV and GnRH neurons
 which are responsible for E2 positive feedback.

Biology of Reproduction

Oxford University Press (OUP)

10.1093/biolre/ioad129

https://doi.org/10.1093/biolre/ioad129
https://academic.oup.com/biolreprod/advance-article-pdf/doi/10.1093/biolre/ioad129/51800250/ioad129.pdf