Regulation of Kiss1 gene expression in the brain of the female mouse
Date
2005-09Author
Smith, Jeremy T.
Steiner, Robert A.
Cunningham, Matthew J.
Clifton, Donald K.
Rissman, Emilie F.
Metadata
Show full item recordAbstract
The Kiss1 gene encodes a family of neuropeptides called kisspeptins, which
activate the receptor G protein-coupled receptor-54 and play a role in the
neuroendocrine regulation of 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 after ovariectomy and decreased with E2
treatment. Conversely, in the anteroventral periventricular nucleus
(AVPV), KiSS-1 expression was reduced after ovariectomy and increased with
E2 treatment. To determine whether the effects of E2 on KiSS-1 are
mediated through estrogen receptor (ER)alpha or ERbeta, we evaluated the
effects of E2 in OVX mice that lacked functional ERalpha or ERbeta. In OVX
mice that lacked functional ERalpha, KiSS-1 mRNA did not respond to E2 in
either the Arc or AVPV, suggesting that ERalpha is essential for mediating
the inhibitory and stimulatory effects of E2. In contrast, KiSS-1 mRNA in
OVX mice that lacked functional ERbeta responded to E2 exactly as
wild-type animals. Double-label in situ hybridization revealed that
virtually all KiSS-1-expressing neurons in the Arc and AVPV coexpress
ERalpha, 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.