Seger M A, van Eekelen J A, Kiss J Z, Burbach J P, de Kloet E R
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Neuroendocrinology. 1988 Apr;47(4):350-7. doi: 10.1159/000124936.
The effect of frontal deafferentation of the medial basal hypothalamus on pro-opiomelanocortin (POMC) gene expression was studied in the intermediate lobe (IL) and anterior lobe (AL) of the pituitary gland in the absence and presence of corticosterone (CORT). The lesion in the basal hypothalamus removed neural inputs to the IL and induced the glucocorticoid receptor (GR) in this tissue. The GR was visualized in the denervated IL by immunocytochemistry. Induction of the GR had a slow onset and was detectable at 3 weeks after lesion, but not at one week after the lesion. In order to study the effect of IL denervation on pro-opiomelanocortin (POMC) gene expression, the level of messenger RNA specifically encoding POMC was measured 1 and 3 weeks after lesion, in the IL and AL. In adrenalectomized (ADX) animals, the changes in POMC mRNA levels were not significant 1 week after lesion in the IL. Three weeks after denervation there was a 3-fold decrease in POMC mRNA in the IL in ADX rats which was blocked by chronic CORT replacement via subcutaneously implanted pellets. In the AL, CORT reduced the level of POMC gene expression in both the lesioned and control animals. It is concluded that (1) removal of neural input induces GR in the denervated IL cells; (2) with the appearance of the GR, POMC gene expression in the IL becomes sensitive to circulating glucocorticoids; (3) under these conditions, CORT may stimulate POMC gene expression in the IL as opposed to its inhibitory effect in the AL.
在有无皮质酮（CORT）的情况下，研究了内侧基底下丘脑额叶去传入对垂体中间叶（IL）和前叶（AL）中阿片-促黑素细胞皮质素原（POMC）基因表达的影响。下丘脑基底病变消除了对IL的神经输入，并诱导了该组织中的糖皮质激素受体（GR）。通过免疫细胞化学在去神经支配的IL中观察到GR。GR的诱导起效缓慢，在损伤后3周可检测到，但在损伤后1周未检测到。为了研究IL去神经支配对POMC基因表达的影响，在损伤后1周和3周测量了IL和AL中特异性编码POMC的信使RNA水平。在肾上腺切除（ADX）的动物中，损伤后1周IL中POMC mRNA水平的变化不显著。去神经支配3周后，ADX大鼠IL中的POMC mRNA下降了3倍，这一现象被通过皮下植入丸剂进行的慢性CORT替代所阻断。在AL中，CORT降低了损伤动物和对照动物中POMC基因的表达水平。得出的结论是：（1）神经输入的去除诱导去神经支配的IL细胞中GR的产生；（2）随着GR的出现，IL中的POMC基因表达对循环糖皮质激素变得敏感；（3）在这些条件下，与它在AL中的抑制作用相反，CORT可能刺激IL中的POMC基因表达。
