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This version published online on May 26, 2005
Endocrinology, doi:10.1210/en.2005-0488
A more recent version of this article appeared on September 1, 2005
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Submitted on April 25, 2005
Accepted on May 17, 2005

Regulation of Kiss1 Gene Expression in the Brain of the Female Mouse

Jeremy T. Smith, Matthew J. Cunningham, Emilie F. Rissman, Donald K Clifton, and Robert A. Steiner*

Departments of Physiology and Biophysicsand Obstetrics and Gynecology, University of Washington, Seattle WA, USA; Department of Biochemistry and Molecular Genetics. University of Virginia, Charlottesville, VA, USA

* To whom correspondence should be addressed. E-mail: steiner{at}u.washington.edu.

The Kiss1 gene encodes a family of neuropeptides called kisspeptins, which activate the receptor GPR54 and play a role in the neuroendocrine regulation of gonadotropin-releasing hormone (GnRH) secretion. We examined whether estradiol (E2) regulates KiSS-1 in the forebrain of the female mouse by comparing KiSS-1 mRNA expression among groups of ovary-intact (diestrus), ovariectomized (OVX), and OVX plus E2-treated mice. In the arcuate nucleus (Arc), KiSS-1 expression increased following ovariectomy and decreased with E2 treatment. Conversely, in the anteroventral periventricular nucleus (AVPV), KiSS-1 expression was reduced following ovariectomy and increased with E2 treatment. To determine whether the effects of E2 on KiSS-1 are mediated through estrogen receptor {alpha} (ER{alpha}) or ER {beta} (ER{beta}), we evaluated the effects of E2 in OVX mice that lacked functional ER{alpha} (ER{alpha}KO) or ER{beta} (ER{beta}KO). In ER{alpha}KO mice, KiSS-1 mRNA did not respond to E2 in either the Arc or AVPV, suggesting that ER{alpha} is essential for mediating the inhibitory and stimulatory effects of E2. In contrast, KiSS-1 mRNA in ER{beta}KO mice responded to E2 exactly as WT animals. Double-label in situ hybridization revealed that virtually all KiSS-1-expressing neurons in the Arc and AVPV coexpress ER{alpha}, suggesting that the effects of E2 are mediated directly through KiSS-1 neurons. We conclude that KiSS-1 neurons in the Arc, which are inhibited by E2, may play a role in the negative feedback regulation of GnRH secretion, whereas KiSS-1 neurons in the AVPV, which are stimulated by E2, may participate in the positive feedback regulation of GnRH secretion.
Key words: KiSS-1 • Metastin • Arcuate • AVPV • Estrogen




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