McCarthy M M, Besmer H R, Jacobs S C, Keidan G M, Gibbs R B
Department of Physiology and the Center for Studies in Reproduction, University of Maryland, Baltimore 21201, USA.
Dev Neurosci. 1997;19(6):488-96. doi: 10.1159/000111246.
The medial preoptic area (mPOA) of the hypothalamus contains a sexually dimorphic nucleus (SDN-POA) that is 5-7 times larger in males than females and which contributes to the development and expression of male-specific sex behaviors in adulthood. Aside from a critical role for estrogen, the mechanisms that establish and maintain this sex difference are largely unknown. Differences in the size of the SDN-POA are thought to be related to estrogen-associated effects on programmed cell death (apoptosis) during early neonatal development. The expression of male sex behavior is also influenced by maternal behavior during development. During the postnatal period, the dam grooms the anogenital region of the pups to stimulate urination and defecation; however, male pups are groomed significantly more often than females and this maternal attention influences the expression of normal male sexual behavior in adulthood. Based on these observations, we hypothesized that different amounts of anogenital sensory stimulation might contribute to the sexually dimorphic development of the SDN-POA, specifically by providing for different levels of neuronal activation in the SDN-POA resulting in different degrees of cell death. Two experiments were conducted to test this hypothesis. In the first experiment, male and female rat pups on postnatal day 3 (PN 3) received simulated anogenital grooming with a stiff bristle paint brush. One hour later, the brains were removed and sections through the POA were cut and processed for the immunocytochemical detection of Fos-like immunoreactivity (IR) as an indicator of neuronal activation. In the second experiment, male and female littermates were killed on PN 3, 5, 7 and 12 and the number of Fos-immunoreactive cells and pyknotic cells detected in the SDN-POA were counted and compared. Our data demonstrate that anogenital stimulation on PN 3 results in a rapid induction of Fos-immunoreactive in the POA of both males and females. However, the majority of Fos-immunoreactive cells were located in the ventral POA and were distinctly lacking in the SDN-POA. In experiment 2, again no Fos-immunoreactive cells were detected in the SDN-POA of animals examined on PN 5-12. However, there was an increase in the number of pyknotic cells in the area surrounding and including the SDN-POA of females relative to males at PN 5, 7 and 12. Collectively, the data suggest that (1) anogenital grooming during early postnatal development induces a rapid activation of cells in the ventral mPOA, but not in the SDN-POA of rats, (2) there is a greater incidence of cell death in and around the SDN-POA of females vs. males during neonatal development, particularly toward the end of the hormone-sensitive critical period, and (3) Fos expression does not appear to be correlated with the sexually dimorphic development of, and/or programmed cell death within, the developing SDN-POA.
下丘脑的内侧视前区（mPOA）包含一个性二态核（SDN-POA），雄性的该核比雌性大5至7倍，它有助于成年期雄性特异性性行为的发育和表现。除了雌激素起关键作用外，建立和维持这种性别差异的机制在很大程度上尚不清楚。SDN-POA大小的差异被认为与新生儿早期发育过程中雌激素对程序性细胞死亡（凋亡）的相关影响有关。雄性性行为的表达在发育过程中也受到母性行为的影响。在出生后的时期，母鼠会舔舐幼崽的肛门生殖器区域以刺激排尿和排便；然而，雄性幼崽被舔舐的频率明显高于雌性，这种母性关注会影响成年后正常雄性性行为的表达。基于这些观察结果，我们推测不同量的肛门生殖器感觉刺激可能有助于SDN-POA的性二态发育，具体而言是通过在SDN-POA中提供不同水平的神经元激活，从而导致不同程度的细胞死亡。进行了两个实验来检验这一假设。在第一个实验中，出生后第3天（PN 3）的雄性和雌性幼鼠用硬毛漆刷接受模拟肛门生殖器舔舐。一小时后，取出大脑，切取通过POA的切片并进行处理，用于免疫细胞化学检测Fos样免疫反应性（IR），作为神经元激活的指标。在第二个实验中，在PN 3、5、7和12处死雄性和雌性同窝幼崽，并对SDN-POA中检测到的Fos免疫反应性细胞和固缩细胞的数量进行计数和比较。我们的数据表明，PN 3时的肛门生殖器刺激会导致雄性和雌性POA中Fos免疫反应性的快速诱导。然而，大多数Fos免疫反应性细胞位于腹侧POA，而SDN-POA中明显缺乏。在实验2中，在PN 5 - 12检查的动物的SDN-POA中同样未检测到Fos免疫反应性细胞。然而，在PN 5、7和12时，雌性相对于雄性，在包括SDN-POA在内的周围区域固缩细胞的数量增加。总体而言，数据表明：（1）出生后早期发育过程中的肛门生殖器舔舐会诱导腹侧mPOA中的细胞快速激活，但不会诱导大鼠SDN-POA中的细胞激活；（2）在新生儿发育期间，尤其是在激素敏感关键期结束时，雌性SDN-POA及其周围的细胞死亡发生率高于雄性；（3）Fos表达似乎与发育中的SDN-POA的性二态发育和/或程序性细胞死亡无关。
