Department of Reproductive Medicine, University of California San Diego, La Jolla, California 92093, USA.
Endocrinology. 2010 Dec;151(12):5807-17. doi: 10.1210/en.2010-0783. Epub 2010 Oct 6.
The Kiss1 gene and its product kisspeptin are important regulators of reproduction. In rodents, Kiss1 is expressed in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV)/rostral periventricular (PeN) nuclei. In the AVPV/PeN, females have more Kiss1 and tyrosine hydroxylase (TH) neurons than males. We explored the ontogeny of the Kiss1 sex difference, and the role of cell death in establishing Kiss1 and TH cell number. We also determined whether Kiss1 cells in AVPV/PeN coexpress TH. AVPV/PeN Kiss1 neurons were first detected in both sexes on postnatal d 10, but the Kiss1 sex difference did not emerge until postnatal d 12. The role of BAX-mediated apoptosis in generating this sex difference was tested in adult Bax knockout (KO) and wild-type mice. Deletion of Bax did not diminish the sex difference in Kiss1 expression in the AVPV/PeN. TH expression was sexually dimorphic in the AVPV of both wild-type and Bax KO mice but, unlike Kiss1, was not sexually dimorphic in the PeN of either genotype. Double-label analysis determined that most Kiss1 neurons coexpress TH mRNA, but many TH neurons do not coexpress Kiss1, especially in the PeN. These findings suggest that several subpopulations of TH cells reside within the AVPV/PeN, only one of which coexpresses Kiss1. In the ARC, Kiss1 cell number was markedly increased in Bax KO mice of both sexes, indicating that although BAX-dependent apoptosis does not generate the sex difference in either Kiss1 or TH expression in AVPV/PeN, BAX does importantly regulate Kiss1 cell number in the ARC.
Kiss1 基因及其产物 kisspeptin 是生殖的重要调节因子。在啮齿动物中，Kiss1 在下丘脑弓状核（ARC）和前腹侧脑室周围核（AVPV）/前脑室周围核（PeN）中表达。在 AVPV/PeN 中，雌性的 Kiss1 和酪氨酸羟化酶（TH）神经元比雄性多。我们探讨了 Kiss1 性别差异的发生机制，以及细胞死亡在建立 Kiss1 和 TH 细胞数量中的作用。我们还确定了 AVPV/PeN 中的 Kiss1 细胞是否共表达 TH。在出生后第 10 天，两性中均首次检测到 AVPV/PeN 的 Kiss1 神经元，但直到出生后第 12 天，Kiss1 的性别差异才显现出来。我们在成年 Bax 敲除（KO）和野生型小鼠中测试了 BAX 介导的细胞凋亡在产生这种性别差异中的作用。Bax 缺失并没有减少 AVPV/PeN 中 Kiss1 表达的性别差异。TH 在野生型和 Bax KO 小鼠的 AVPV 中均表现出性别二态性，但与 Kiss1 不同，在两种基因型的 PeN 中均无性别二态性。双标记分析确定，大多数 Kiss1 神经元共表达 TH mRNA，但许多 TH 神经元不共表达 Kiss1，尤其是在 PeN 中。这些发现表明，TH 细胞的几个亚群存在于 AVPV/PeN 中，只有其中一个亚群共表达 Kiss1。在 ARC 中，两性的 Bax KO 小鼠的 Kiss1 细胞数量显著增加，表明尽管 BAX 依赖性细胞凋亡不会导致 AVPV/PeN 中 Kiss1 或 TH 表达的性别差异，但 BAX 确实重要地调节 ARC 中的 Kiss1 细胞数量。
