Eghbal-Ahmadi M, Hatalski C G, Avishai-Eliner S, Baram T Z
Department of Anatomy & Neurobiology, University of California, Irvine 92697-4475, USA.
Endocrinology. 1997 Nov;138(11):5048-51. doi: 10.1210/endo.138.11.5647.
The stress neurohormone corticotropin releasing factor (CRF) activates at least two receptor types. Expression of corticotropin releasing factor receptor type II (CRF2) has been demonstrated in the hypothalamic ventromedial nucleus (VMH) of the adult and developing rat, but the physiological functions of VMH-CRF2 have not been elucidated. The VMH has been documented as an important participant in the regulation of food intake and its interactions with the hypothalamic-pituitary-adrenal axis and circadian rhythms. Regulation of VMH-CRF2 may thus play a role in the interplay of physiological alterations in metabolic state with the neuroendocrine and anorexic effects of CRF. This study determined the regulation of CRF2-mRNA expression in infant rats by the physiological consequences of maternal deprivation, i.e., fasting and stress. Using in situ hybridization, maternally deprived pups had an average 62% reduction of VMH-CRF2-mRNA levels compared with stress-free controls. Maternal deprivation also resulted in elevated plasma corticosterone levels (3.8 +/- 0.3 vs. 1.3 +/- 0.1 microg/dl) and an average 5.7% body weight loss. This study demonstrates that maternal deprivation, via fasting and HPA activation, leads to a dramatic decrease of CRF2-mRNA levels in the VMH. These results are consistent with a role for CRF2 activation in mediating some of the complex interactions of CRF (or urocortin) with regulation of food intake in the developing rat.
应激神经激素促肾上腺皮质激素释放因子(CRF)可激活至少两种受体类型。促肾上腺皮质激素释放因子II型受体(CRF2)已在成年和发育中的大鼠下丘脑腹内侧核(VMH)中得到证实,但其生理功能尚未阐明。VMH被证明是调节食物摄入以及与下丘脑-垂体-肾上腺轴和昼夜节律相互作用的重要参与者。因此,VMH-CRF2的调节可能在代谢状态的生理改变与CRF的神经内分泌和厌食作用之间的相互作用中发挥作用。本研究通过母体剥夺的生理后果,即禁食和应激,来确定幼鼠中CRF2-mRNA表达的调节情况。使用原位杂交技术,与无应激对照组相比,母体剥夺的幼崽VMH-CRF2-mRNA水平平均降低了62%。母体剥夺还导致血浆皮质酮水平升高(3.8±0.3对1.3±0.1微克/分升),体重平均减轻5.7%。本研究表明,母体剥夺通过禁食和HPA激活,导致VMH中CRF2-mRNA水平显著下降。这些结果与CRF2激活在介导CRF(或尿皮质素)与发育中大鼠食物摄入调节的一些复杂相互作用中的作用一致。