Seymour Patricia L, Dettloff Samantha L, Jones Juli E, Wade George N
Center for Neuroendocrine Studies, University of Massachusetts, 135 Hicks Way, Amherst, MA 01003, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R418-R423. doi: 10.1152/ajpregu.00168.2005. Epub 2005 Apr 14.
Caloric deprivation inhibits reproduction, including copulatory behaviors, in female mammals. Decreases in metabolic fuel availability are detected in the hindbrain, and this information is relayed to the forebrain circuits controlling estrous behavior by neuropeptide Y (NPY) projections. In the forebrain, the nutritional inhibition of estrous behavior appears to be mediated by corticotropin-releasing factor (CRF) or urocortin-signaling systems. Intracerebroventricular (ICV) infusion of the CRF antagonist, astressin, prevents the suppression of lordosis by food deprivation and by NPY treatment in Syrian hamsters. These experiments sought to determine which CRF receptor type(s) is involved. ICV infusion of the CRF receptor subtype CRFR2-selective agonists urocortin 2 and 3 (UCN2, UCN3) inhibited sexual receptivity in hormone-primed, ovariectomized hamsters. Furthermore, the CRFR2-selective antagonist, astressin 2B, prevented the inhibition of estrous behavior by UCN2 and by NPY, consistent with a role for CRFR2. On the other hand, astressin 2B did not prevent the inhibition of behavior induced by 48-h food deprivation or ICV administration of CRF, a mixed CRFR1 and CRFR2 agonist, suggesting that activation of CRFR1 signaling is sufficient to inhibit sexual receptivity in hamsters. Although administration of CRFR1-selective antagonists (NBI-27914 and CP-154,526) failed to reverse the inhibition of receptivity by CRF treatment, we could not confirm their biological effectiveness in hamsters. The most parsimonious interpretation of these findings is that, although NPY inhibits estrous behavior via downstream CRFR2 signaling, food deprivation may exert its inhibition via both CRFR1 and CRFR2 and that redundant neuropeptide systems may be involved.
热量剥夺会抑制雌性哺乳动物的繁殖，包括交配行为。后脑会检测到代谢燃料可用性的降低，并且这些信息通过神经肽Y（NPY）投射传递到控制发情行为的前脑回路。在前脑中，发情行为的营养抑制似乎是由促肾上腺皮质激素释放因子（CRF）或尿皮质素信号系统介导的。脑室内（ICV）注入CRF拮抗剂阿斯特辛，可防止食物剥夺和NPY处理对叙利亚仓鼠弓背姿势的抑制。这些实验旨在确定涉及哪种CRF受体类型。脑室内注入CRF受体亚型CRFR2选择性激动剂尿皮质素2和3（UCN2、UCN3）可抑制激素预处理的去卵巢仓鼠的性接受能力。此外，CRFR2选择性拮抗剂阿斯特辛2B可防止UCN2和NPY对发情行为的抑制，这与CRFR2的作用一致。另一方面，阿斯特辛2B不能防止48小时食物剥夺或脑室内注射CRF（一种混合的CRFR1和CRFR2激动剂）诱导的行为抑制，这表明CRFR1信号的激活足以抑制仓鼠的性接受能力。尽管给予CRFR1选择性拮抗剂（NBI-27914和CP-154,526）未能逆转CRF处理对接受能力的抑制，但我们无法证实它们在仓鼠中的生物学有效性。对这些发现最简洁的解释是，尽管NPY通过下游CRFR2信号抑制发情行为，但食物剥夺可能通过CRFR1和CRFR2两者发挥其抑制作用，并且可能涉及冗余的神经肽系统。
