Estradiol benzoate infusion into the stalk median eminence (S-ME) of ovariectomized female rhesus monkeys rapidly stimulates kisspeptin release. — ASN Events
  1. Schedule
  2. Submitted Orals 2: Reproduction 1
  3. Estradiol benzoate infusion into the stalk median eminence (S-ME) of ovariectomized female rhesus monkeys rapidly stimulates kisspeptin release.

Estradiol benzoate infusion into the stalk median eminence (S-ME) of ovariectomized female rhesus monkeys rapidly stimulates kisspeptin release. (#80)

Brian P Kenealy 1 , Kim L Keen 1 , James P Garcia 1 2 , Joseph R Kurian 1 , Ei Terasawa 1 3
  1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
  2. Endocrinology and Reproductive Physiology Training Program, University of Wisconsin-Madison, Madison, WI, USA
  3. Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA

Pulsatile GnRH release in the S-ME is essential for reproductive function. Recently we discovered that estradiol (E2), synthesized and released in the S-ME of ovariectomized female monkeys, plays a role in regulation of GnRH release. Specifically, using a microdialysis method, we found that a brief infusion of estradiol benzoate (EB) into the S-ME rapidly stimulates GnRH release. This EB-induced GnRH release appears to represent local action of neuroestradiol in the S-ME: 1) EB infusion to the S-ME induced oscillatory E2 increases (peaks reached 700-1500 pg/ml), 2) electrical stimulation of the hypothalamus induced E2 increases, and 3) infusion of the aromatase inhibitor letrozole into the S-ME blocked EB-induced GnRH release 1. Changes in E2 in dialysates, measured by LC/MS/MS, are not due to hydrolysis/metabolism of EB. To further examine the role of local neuroestradiol in regulation of GnRH release, in the present study we investigated the effects of EB on kisspeptin release in the S-ME of ovariectomized monkeys. After 60 min of control sampling, EB was infused through the microdialysis probe for 20 min, while dialysates were continuously collected for 80 min. Kisspeptin concentrations in dialysates were assessed by RIA. The results indicate that EB stimulated kisspeptin release with a latency, peak duration, and interpulse-interval similar to those with the EB-induced GnRH release, although the magnitude of EB-induced kisspeptin release was smaller than the EB-induced GnRH release. These results are interpreted to mean that the EB-induced GnRH release and kisspeptin release occur independently, as GnRH release is stimulated by kisspeptin in ovarian intact, but not ovariectomized monkeys 2. Whether the aromatase inhibitor letrozole blocks the EB-induced kisspeptin release remains to be investigated. Nevertheless, the results suggest that neuroestradiol release in the S-ME may have broad neurostimulatory properties, facilitating release of both GnRH and kisspeptin.

  1. Kenealy BP, Kapoor A, Guerriero KA, Keen KL, Garcia JP, Kurian JR, Ziegler TE, Terasawa E. 2013 Neuroestradiol in the hypothalamus contributes to the regulation of gonadotropin releasing hormone release. J. Neurosci. 33: 19051-19059.
  2. Guerriero KA, Keen KL, Millar RP, Terasawa E. 2012 Developmental changes in GnRH release in response to kisspeptin agonist and antagonist in female rhesus monkeys (Macaca mulatta): implications for the mechanism of puberty. Endocrinology 153: 825-836.