Lehman M N, Goodman R L, Karsch F J, Jackson G L, Berriman S J, Jansen H T
Department of Cell Biology, University of Cincinnati College of Medicine, OH 45267-0521, USA.
Brain Res Bull. 1997;44(4):445-57. doi: 10.1016/s0361-9230(97)00225-6.
Seasonal breeders, such as sheep and hamsters, by virtue of their annual cycles of reproduction, represent valuable models for the study of plasticity in the adult mammalian neuroendocrine brain. A major factor responsible for the occurrence of seasonal reproductive transitions is a striking change in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the inhibitory effects of gonadal steroids. However, the neural circuitry mediating these seasonal changes is still relatively unexplored. In this article, we review recent findings that have begun to define that circuitry and its plasticity in a well-studied seasonal breeder, the ewe. Tract tracing studies and immunocytochemical analyses using Fos and FRAs as markers of activation point to a subset of neuroendocrine GnRH neurons in the MBH as potential mediators of pulsatile GnRH secretion. Because the vast majority of GnRH neurons lack estrogen receptors, seasonal changes in responsiveness to estradiol are most probably conveyed by afferents. Two possible mediators of this influence are dopaminergic cells in the A14/A15 cell groups of the hypothalamus, and estrogen receptor-containing cells in the arcuate nucleus that project to the median eminence. The importance of GnRH afferents in the regulation of season breeding is underscored by observations of seasonal changes in the density of synaptic inputs onto GnRH neurons. Thyroid hormones may participate in this remodeling, because they are important in seasonal reproduction, influence the morphology of other brain systems, and thyroid hormone receptors are expressed within GnRH neurons. Finally, in the hamster, neonatal hypothyroidism affects the number of caudally placed GnRH neurons in the adult brain, suggesting that thyroid hormones may influence development of the GnRH system as well as its reproductive functions in the adult brain.
季节性繁殖动物，如绵羊和仓鼠，凭借其年度繁殖周期，成为研究成年哺乳动物神经内分泌脑可塑性的宝贵模型。导致季节性繁殖转变发生的一个主要因素是促性腺激素释放激素（GnRH）神经元对性腺类固醇抑制作用的反应性发生显著变化。然而，介导这些季节性变化的神经回路仍相对未被探索。在本文中，我们回顾了最近的研究发现，这些发现已开始在一种经过充分研究的季节性繁殖动物——母羊中定义该神经回路及其可塑性。使用Fos和FRA作为激活标记的示踪研究和免疫细胞化学分析表明，下丘脑弓状核中的一部分神经内分泌GnRH神经元可能是GnRH脉冲式分泌的潜在介导者。由于绝大多数GnRH神经元缺乏雌激素受体，对雌二醇反应性的季节性变化很可能是由传入神经传递的。这种影响的两个可能介导者是下丘脑A14/A15细胞群中的多巴胺能细胞，以及投射到正中隆起的弓状核中含雌激素受体的细胞。对GnRH神经元突触输入密度季节性变化的观察强调了GnRH传入神经在季节性繁殖调节中的重要性。甲状腺激素可能参与了这种重塑，因为它们在季节性繁殖中很重要，影响其他脑系统的形态，并且GnRH神经元中表达甲状腺激素受体。最后，在仓鼠中，新生儿甲状腺功能减退会影响成年大脑中尾侧GnRH神经元的数量，这表明甲状腺激素可能影响GnRH系统的发育及其在成年大脑中的生殖功能。
