Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands.
Endocrinology. 2013 Aug;154(8):2739-49. doi: 10.1210/en.2013-1120. Epub 2013 Jun 6.
In rodents, kisspeptin-expressing neurons are localized in 2 hypothalamic brain nuclei (anteroventral periventricular nucleus/periventricular nucleus continuum [AVPv/PeN] and arcuate nucleus [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 postnatal ages (postnatal day 5 [P5] to P25), whereas WT males did not show any expression before 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 (E(2)) or DHT. In the ARC, kisspeptin peptide expression decreased after gonadectomy but was completely rescued by either E(2) or DHT treatment in each sex/genotype. However, kisspeptin peptide expression was lower in ArKO compared with WT subjects. In the AVPv/PeN, ArKO females showed a male-typical kisspeptin peptide expression, and adult E(2) treatment partially restored kisspeptin peptide expression. Finally, we showed that, after E2 treatment of WT and ArKO mice between either P5 and P15 or P15 and P25, AVPv/PeN kisspeptin 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 E(2).
在啮齿动物中， kisspeptin 表达神经元位于 2 个下丘脑脑核（前腹侧室旁核/室旁核连续体（AVPv/PeN）和弓状核（ARC）），并受性激素调节。通过使用野生型（WT）和芳香酶敲除（ArKO）小鼠（不能将睾酮转化为雌二醇）和免疫组织化学，我们观察到 WT 雌性在整个产后年龄（产后第 5 天[P5]至 P25）中，ARC 中的 kisspeptin 肽表达持续增加，而 WT 雄性在 P25 之前没有任何表达。ARC 中也存在 kisspeptin 肽表达，但在这个早期产后阶段没有增加，这表明 ARC 中的 kisspeptin 肽表达是由雌二醇依赖和非依赖机制组织的。我们还比较了成年雄性和雌性小鼠之间的 kisspeptin 肽表达，这些小鼠要么性腺完整，要么性腺切除术，并用雌二醇（E(2)）或二氢睾酮（DHT）处理或不处理。在 ARC 中，性腺切除术后 kisspeptin 肽表达减少，但在每一种性别/基因型中，E(2)或 DHT 处理均可完全挽救。然而，ArKO 与 WT 相比，ArKO 的 kisspeptin 肽表达较低。在 AVPv/PeN 中，ArKO 雌性表现出典型的雄性 kisspeptin 肽表达，而成年 E(2)处理部分恢复了 kisspeptin 肽表达。最后，我们表明，在 WT 和 ArKO 小鼠之间，无论是在 P5 和 P15 之间还是 P15 和 P25 之间用 E2 处理后，AVPv/PeN kisspeptin 肽表达仍可在 P5 时雄性化，但从 P15 开始女性化。总之，这 2 种 kisspeptin 神经元群体（AVPv/PeN 与 ARC）似乎通过 E(2)以不同的方式组织和激活。
