Sex Steroid Regulation of Kisspeptin Circuits - Kisspeptin Signaling in Reproductive Biology - page 274

Fig. 13.3 In females, estradiol (E2) regulation of Kiss1 in the anteroventral periventricular nucleus
(AVPV) and arcuate nucleus (ARC) is mediated via estrogen receptor ) signaling. ( a ) Data

show the effects of ovariectomy (OVX) with or without estradiol (E2) replacement on Kiss1
mRNA in the AVPV and ARC of wild-type (WT) and ER

α (ER α

α knockout (ER α KO) mice. Note the

lack of effect in ER KO mice. Asterisk , P < 0.05. Data taken from Smith JT, Cunningham MJ,

Rissman EF, Clifton DK, Steiner RA 2005 Regulation of Kiss1 gene expression in the brain of
the female mouse. Endocrinology 146:3686-3692 with permission from The Endocrine Society.
( b ) Schematic diagram demonstrating the likely pathways leading to Kiss1 regulation by E2 in the
female. ER

α

α estrogen receptor α

sought to determine the independent role of progesterone on kisspeptin neurons), or
be more likely due to reduced progesterone receptor expression in the absence of
estradiol in OVX ewes [ 55 ]. Not surprisingly, all kisspeptin neurons in the ovine
ARC express ER [ 28 ], as well as progesterone receptor [ 27 ] (determined in ovary-

intact animals during the luteal phase), but a much smaller proportion of kisspeptin
cells in the POA appears to do so [ 28 ]. In the ovine POA, estradiol treatment
increases Kiss1 mRNA expression [ 27 ], as it does in the rodent AVPV, and so the
differential regulation of kisspeptin persists in this animal model, again suggesting
different regions controlling negative (ARC) and positive feedback (POA). In this
species, however, an additional layer of complexity exists (as described earlier) in that
estradiol-induced positive feedback is generated from the mediobasal hypothalamus

α