Spinedi E, Giacomini M, Jacquier M C, Gaillard R C
Department of Medicine, University Hospital, Geneva, Switzerland.
Neuroendocrinology. 1991 Feb;53(2):160-70. doi: 10.1159/000125713.
Bilateral adrenalectomy (ADX) leads to increased ACTH synthesis and secretion. It is thought that endogenous glucocorticoids exert a feedback mechanism at both pituitary and brain levels. The present study has been performed in order to determine the effect of ADX on the release of hypothalamic neuropeptides with corticotropin-releasing activity (CRA) and if there exists a median eminence site of glucocorticoid action to regulate hypothalamic-pituitary-adrenal (HPA) function. Adrenalectomized and sham-operated male rats were killed at different periods after surgery (2, 5, 7 and 14 days) and trunk blood was collected for ACTH and corticosterone (B) concentrations measurement. Brain (median eminence, ME; and medial basal hypothalamus, MBH) and pituitary (anterior lobe, AP; and neurointermediate lobe, NIL) tissues were dissected in order to evaluate either peptide content or in vitro hormone release. The results indicate that ADX blunted plasma B levels and increased AP ACTH content and secretion in a time-related fashion up to the 14th day. ADX significantly decreased both CRF and CRA contents in the ME at all periods studied; ME arginine-vasopressin (AVP) increased 7 and 14 days after ADX. MBH CRF decreased after ADX, but returned to sham value 2 weeks later; similarly, MBH AVP decreased at all periods after ADX. Removal of endogenous glucocorticoids did not vary neither oxytocin (OXY) content in the ME and MBH nor AVP and OXY contents in the NIL. In our superfusion experiments, we found that ADX increased basal AVP release and did not change spontaneous CRF secretion from ME terminals. Dexamethasone (Dxm, 10 nM) diminished AVP but not CRF output by ME tissues from adrenalectomized rats. A direct relationship was found between ME CRF and 28 mM KCl (hK+)-induced CRF release by MEs from adrenalectomized rats. ME fragments from adrenalectomized rats were hyperresponsive to kH+ stimulation of AVP release. Dxm (10 nM) decreased the hK(+)-evoked CRF and AVP release by MEs from adrenalectomized rats. ADX and dexamethasone treatment did not influence basal and hK(+)-elicited ME OXY release. Additionally, a rapid glucocorticoid inhibitory effect on ACTH secretion by isolated AP cells from both sham and adrenalectomized rats was found, and an in vitro corticotrope hyporesponse to 0.63 nM CRF and 9.25 nM AVP stimulation during several days after ADX.(ABSTRACT TRUNCATED AT 400 WORDS)
双侧肾上腺切除术（ADX）会导致促肾上腺皮质激素（ACTH）合成和分泌增加。据认为，内源性糖皮质激素在垂体和脑水平均发挥反馈机制。进行本研究是为了确定ADX对具有促肾上腺皮质激素释放活性（CRA）的下丘脑神经肽释放的影响，以及是否存在糖皮质激素作用的正中隆起部位来调节下丘脑-垂体-肾上腺（HPA）功能。在手术后不同时间段（2、5、7和14天）处死肾上腺切除和假手术的雄性大鼠，并采集躯干血以测量ACTH和皮质酮（B）浓度。解剖脑（正中隆起，ME；和内侧基底下丘脑，MBH）和垂体（前叶，AP；和神经中间叶，NIL）组织，以评估肽含量或体外激素释放。结果表明，ADX使血浆B水平降低，并使AP中ACTH含量和分泌以时间相关的方式增加，直至第14天。在所有研究时间段，ADX均显著降低ME中促肾上腺皮质激素释放因子（CRF）和CRA的含量；ADX后7天和14天，ME中精氨酸加压素（AVP）增加。ADX后MBH中CRF降低，但2周后恢复到假手术值；同样，ADX后所有时间段MBH中AVP均降低。去除内源性糖皮质激素对ME和MBH中催产素（OXY）含量以及NIL中AVP和OXY含量均无影响。在我们的灌注实验中，我们发现ADX增加基础AVP释放，且不改变ME终末的自发CRF分泌。地塞米松（Dxm，10 nM）减少肾上腺切除大鼠ME组织的AVP释放，但不改变CRF释放。发现肾上腺切除大鼠ME中CRF与28 mM KCl（hK +）诱导的CRF释放之间存在直接关系。肾上腺切除大鼠的ME片段对kH +刺激AVP释放反应过度。Dxm（10 nM）减少肾上腺切除大鼠ME中hK（+）诱发的CRF和AVP释放。ADX和地塞米松处理不影响基础和hK（+）诱发的ME OXY释放。此外，发现糖皮质激素对假手术和肾上腺切除大鼠分离的AP细胞分泌ACTH有快速抑制作用，并且在ADX后数天内，体外促肾上腺皮质细胞对0.63 nM CRF和9.25 nM AVP刺激反应低下。（摘要截取自400字）
