The Two Kisspeptin Neuronal Populations Are Differentially Organized and Activated by Estradiol in Mice

In rodents, kisspeptin-expressing neurons are localized in 2 hypothalamic brain nuclei (anteroventralperiventricularnucleus/periventricularnucleuscontinuum[AVPv/PeN]andarcuatenucleus [ARC]) and modulated by sex steroids. By using wild-type (WT) and aromatase knockout (ArKO) mice (which cannot convert testosterone into estradiol) and immunohistochemistry, we observed that WT females showed a continuous increase in kisspeptin peptide expression in the ARC across postnatalages(postnatalday5[P5]toP25),whereasWTmalesdidnotshowanyexpressionbefore P25. Kisspeptin peptide expression was also present in ArKO females but did not increase over this early postnatal period, suggesting that kisspeptin peptide expression in the ARC is organized by estradiol-dependent and -independent mechanisms. We also compared kisspeptin peptide expression between groups of adult male and female mice that were left gonadally intact or gonadectomized and treated or not with estradiol (E2) or DHT. In the ARC, kisspeptin peptide expression decreased after gonadectomy but was completely rescued by either E2 or DHT treatment in eachsex/genotype.However,kisspeptinpeptideexpressionwaslowerinArKOcomparedwithWT subjects.IntheAVPv/PeN,ArKOfemalesshowedamale-typicalkisspeptinpeptideexpression,and adult E2 treatment partially restored kisspeptin peptide expression. Finally, we showed that, after E2treatmentofWTandArKOmicebetweeneitherP5andP15orP15andP25,AVPv/PeNkisspeptin peptide expression could be still masculinized at P5, but was feminized from P15 onward. In conclusion, the 2 kisspeptin neuronal populations (AVPv/PeN vs ARC) seem to be differentially organized and activated by E2. (Endocrinology 154: 2739–2749, 2013)