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


ABSTRACT: Negative and positive feedback effects of ovarian 17?-estradiol (E2) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo-pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a part of estrogen's positive feedback loop. In experiment 1, E2 benzoate-induced LH surges in ovariectomized female monkeys were severely attenuated by systemic administration of the aromatase inhibitor, letrozole. Aromatase is the enzyme responsible for synthesis of E2 from androgens. In experiment 2, using microdialysis, GnRH and kisspeptin surges induced by E2 benzoate were similarly attenuated by infusion of letrozole into the median eminence of the hypothalamus. Therefore, neuroestradiol is an integral part of the hypothalamic engagement in response to elevated circulating E2 Collectively, we will need to modify the concept of estrogen's positive feedback mechanism.

SUBMITTER: Kenealy BP 

PROVIDER: S-EPMC5748216 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Kenealy Brian P BP   Keen Kim L KL   Garcia James P JP   Kohlenberg Lucille K LK   Terasawa Ei E  

Proceedings of the National Academy of Sciences of the United States of America 20171211 52


Negative and positive feedback effects of ovarian 17β-estradiol (E<sub>2</sub>) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo-pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a part of estrogen's positive feedback loop. In experiment 1, E<sub>2</sub> benzoate-induced LH surges  ...[more]

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