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Significance The concept that ovarian cycles in female mammals are regulated by gonadal steroids released from the ovary is well-established dogma. The findings of this study, however, showing that the removal of neuroestradiol synthesis in the median eminence of the hypothalamus by the aromatase inhibitor, letrozole, greatly attenuates estrogen-induced gonadotropin releasing hormone and luteinizing hormone surges in ovariectomized female monkeys, indicate that neuroestradiol locally synthesized and released in the hypothalamus is an integral part of the ovary-initiated positive feedback mechanism of estradiol.

Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys