Wade George N, Jones Juli E
Center for Neuroendocrine Studies, University of Massachusetts, 135 Hicks Way, Amherst, MA 01003, USA.
Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1277-96. doi: 10.1152/ajpregu.00475.2004.
Natural selection has linked the physiological controls of energy balance and fertility such that reproduction is deferred during lean times, particularly in female mammals. In this way, an energetically costly process is confined to periods when sufficient food is available to support pregnancy and lactation. Even in the face of abundance, nutritional infertility ensues if energy intake fails to keep pace with expenditure. A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels (e.g., undereating, excessive energy expenditure, diabetes mellitus) can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors. Decreases in metabolic fuel availability appear to be detected by cells in the caudal hindbrain. Hindbrain neurons producing neuropeptide Y (NPY) and catecholamines (CA) then project to the forebrain where they contact GnRH neurons both directly and also indirectly via corticotropin-releasing hormone (CRH) neurons to inhibit GnRH secretion. In the case of estrous behavior, the best available evidence suggests that the inhibitory NPY/CA system acts primarily via CRH or urocortin projections to various forebrain loci that control sexual receptivity. Disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits, indicating that the circuitry responds to energy deficits and that no signal is necessary to indicate that there is an adequate energy supply. While there is a large body of evidence to support this hypothesis, the data do not exclude nutritional inhibition of reproduction by other pathways and processes, and the full story will undoubtedly be more complex than this.
自然选择将能量平衡和生育能力的生理控制联系起来，使得繁殖在食物匮乏时期被推迟，尤其是在雌性哺乳动物中。通过这种方式，一个能量消耗巨大的过程被限制在有足够食物来支持怀孕和哺乳的时期。即使在食物充足的情况下，如果能量摄入跟不上消耗，也会出现营养性不孕。本文提出了一个可行的假说，即任何限制可氧化燃料可用性的活动或状况（例如，饮食不足、能量消耗过多、糖尿病）都可能抑制促性腺激素释放激素（GnRH）/促黄体生成素的分泌以及雌性的交配行为。代谢燃料可用性的降低似乎是由尾侧后脑的细胞检测到的。产生神经肽Y（NPY）和儿茶酚胺（CA）的后脑神经元随后投射到前脑，在那里它们直接以及通过促肾上腺皮质激素释放激素（CRH）神经元间接接触GnRH神经元，从而抑制GnRH的分泌。就发情行为而言，现有最好的证据表明，抑制性的NPY/CA系统主要通过CRH或尿皮质素投射到控制性接受能力的各种前脑位点来发挥作用。这些信号传导过程的中断使得正常繁殖能够在能量不足的情况下继续进行，这表明该神经回路对能量不足做出反应，并且不需要信号来表明有足够的能量供应。虽然有大量证据支持这一假说，但这些数据并不排除其他途径和过程对繁殖的营养抑制作用，而且实际情况无疑会比这更复杂。
