Dagerlind A, Schalling M, Eneroth P, Goldstein M, Hökfelt T
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Neurochem Int. 1990;17(2):343-56. doi: 10.1016/0197-0186(90)90157-o.
Reserpine treatment has been shown to cause a long-lasting decrease in phenylethanolamine N-methyltransferase mRNA levels and a simultaneous increase in tyrosine hydroxylase and neuropeptide tyrosine mRNA levels in chromaffin cells of rat adrenal medulla. In this study, in situ hybridization histochemistry was used to further investigate factors involved in the differential regulation of the catecholamine synthesizing enzymes and the coexisting peptide neuropeptide tyrosine. Pretreatment with the synthetic glucocorticoid analogue dexamethasone followed by the administration of a single dose of reserpine completely reversed the decrease in phenylethanolamine N-methyltransferase mRNA seen after reserpine treatment alone, but had no effect on the reserpine-induced increase in tyrosine hydroxylase mRNA. Dexamethasone alone did not change phenylethanolamine N-methyltransferase or tyrosine hydroxylase mRNA levels in the adrenal medulla. When reserpine-treated rats were given adrenocorticotropic hormone a partial reversal of the decrease in phenylethanolamine N-methyltransferase mRNA was seen. Furthermore, the reserpine-induced increase in neuropeptide tyrosine mRNA levels was markedly reduced when animals were pretreated with dexamethasone, whereas dexamethasone alone had no effect on neuropeptide tyrosine mRNA levels. The drop in phenylethanolamine N-methyltransferase mRNA levels after reserpine treatment was not due to a depression of the pituitary adrenal axis, since proopiomelanocortin mRNA levels in the anterior pituitary increased and plasma corticosterone levels were stable following reserpine treatment. A possible local regulation within the adrenal gland that may involve the glucocorticoid receptor and/or other factors is discussed.
利血平治疗已显示可导致大鼠肾上腺髓质嗜铬细胞中苯乙醇胺N - 甲基转移酶mRNA水平长期下降，同时酪氨酸羟化酶和神经肽Y mRNA水平升高。在本研究中，采用原位杂交组织化学进一步研究参与儿茶酚胺合成酶和共存肽神经肽Y差异调节的因素。用合成糖皮质激素类似物地塞米松预处理，然后给予单剂量利血平，可完全逆转单独使用利血平治疗后出现的苯乙醇胺N - 甲基转移酶mRNA水平下降，但对利血平诱导的酪氨酸羟化酶mRNA升高没有影响。单独使用地塞米松不会改变肾上腺髓质中苯乙醇胺N - 甲基转移酶或酪氨酸羟化酶mRNA水平。当给利血平处理的大鼠注射促肾上腺皮质激素时，可观察到苯乙醇胺N - 甲基转移酶mRNA水平下降的部分逆转。此外，当动物用地塞米松预处理时，利血平诱导的神经肽Y mRNA水平升高明显降低，而单独使用地塞米松对神经肽Y mRNA水平没有影响。利血平治疗后苯乙醇胺N - 甲基转移酶mRNA水平的下降并非由于垂体 - 肾上腺轴的抑制，因为利血平治疗后垂体前叶中阿片促黑激素皮质素原mRNA水平升高，血浆皮质酮水平稳定。本文讨论了肾上腺内可能涉及糖皮质激素受体和/或其他因素的局部调节。
