Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
Front Endocrinol (Lausanne). 2011 Dec 1;2:80. doi: 10.3389/fendo.2011.00080. eCollection 2011.
The secretory output of gonadotropin-releasing hormone (GnRH) neurons is critically influenced by peptidergic neurons synthesizing kisspeptins (KP) and neurokinin B (NKB) in the hypothalamic infundibular nucleus (Inf). These cells mediate negative feedback effects of sex steroids on the reproductive axis. While negative feedback is lost in postmenopausal women, it is partly preserved by the sustained testosterone secretion in aged men. We hypothesized that the different reproductive physiology of aged men and women is reflected in morphological differences of KP and NKB neurons. This sexual dimorphism was studied with immunohistochemistry in hypothalamic sections of aged human male (≥50 years) and female (>55 years) subjects. KP and NKB cell bodies of the Inf were larger in females. The number of KP cell bodies, the density of KP fibers, and the incidence of their contacts on GnRH neurons were much higher in aged women compared with men. The number of NKB cell bodies was only slightly higher in women and there was no sexual dimorphism in the regional density of NKB fibers and the incidence of their appositions onto GnRH cells. The incidences of NKB cell bodies, fibers, and appositions onto GnRH neurons exceeded several-fold those of KP-IR elements in men. More NKB than KP inputs to GnRH cells were also present in women. Immunofluorescent studies identified only partial overlap between KP and NKB axons. KP and NKB were colocalized in higher percentages of afferents to GnRH neurons in women compared with men. Most of these sex differences might be explained with the lack of estrogen negative feedback in aged women, whereas testosterone can continue to suppress KP, and to a lesser extent, NKB synthesis in men. Overall, sex differences in reproductive physiology of aged humans were reflected in the dramatic sexual dimorphism of the KP system, with significantly higher incidences of KP-IR neurons, fibers and inputs to GnRH neurons in aged females vs. males.
促性腺激素释放激素（GnRH）神经元的分泌输出受到下丘脑漏斗核（Inf）中合成 kisspeptins（KP）和神经激肽 B（NKB）的肽能神经元的严格影响。这些细胞介导性激素对生殖轴的负反馈作用。虽然绝经后妇女的负反馈作用丧失，但在老年男性中，由于持续分泌睾酮，部分得到保留。我们假设，老年男性和女性的不同生殖生理学反映在 KP 和 NKB 神经元的形态差异上。这项研究使用免疫组织化学方法，对年龄在 50 岁以上的老年男性和 55 岁以上的老年女性的下丘脑切片进行了研究。Inf 中的 KP 和 NKB 细胞体在女性中更大。与男性相比，老年女性的 KP 细胞体数量、KP 纤维密度以及与 GnRH 神经元接触的发生率都要高得多。女性的 NKB 细胞体数量仅略高，而 NKB 纤维的区域密度和与 GnRH 细胞的接触发生率没有性别二态性。NKB 细胞体、纤维和与 GnRH 神经元的接触发生率在男性中是 KP-IR 元素的数倍以上。与男性相比，NKB 对 GnRH 细胞的输入多于 KP。免疫荧光研究仅发现 KP 和 NKB 轴突之间存在部分重叠。与男性相比，女性中 GnRH 神经元的 KP 和 NKB 传入的比例更高。这些性别差异中的大多数可能可以用绝经后女性缺乏雌激素负反馈来解释，而睾酮可以继续抑制 KP，并在较小程度上抑制男性的 NKB 合成。总的来说，人类老年的生殖生理学的性别差异反映在 KP 系统的显著性别二态性上，与男性相比，老年女性的 KP-IR 神经元、纤维和对 GnRH 神经元的输入发生率更高。
