Hooi S C, Maiter D M, Martin J B, Koenig J I
Laboratory of Neuroendocrinology, Neurology Service, Massachusetts General Hospital, Boston 02114.
Endocrinology. 1990 Nov;127(5):2281-9. doi: 10.1210/endo-127-5-2281.
Galanin (GAL), a 29-amino acid peptide, affects the secretion of several anterior pituitary hormones, including PRL and GH. Since GAL coexists with vasopressin and CRH in the hypothalamic paraventricular nucleus (PVN), we have studied the pharmacological and physiological actions of GAL on ACTH and TSH secretion in freely moving male rats. Cannulae were surgically implanted in the right atria and brain, intraventricular or adjacent to the PVN, of adult Sprague-Dawley rats. Seven days later, GAL (500 or 1000 ng) or saline was infused into the PVN, and serial blood samples were obtained 5, 10, 20, and 40 min after the infusion. Some animals were also stressed by the inhalation of ether vapors for 2 min after the PVN infusion. Basal ACTH concentrations were increased 2-fold in saline-treated rats; however, plasma ACTH levels were unchanged after GAL infusion. The exposure of rats to ether vapors for 2 min after the infusion of saline into the PVN increased plasma ACTH concentrations from 22.8 +/- 6.0 to 596.6 +/- 59.9 pg/ml 10 min later. However, the infusion of GAL into the PVN attenuated stress-induced ACTH secretion. After GAL infusion, peak ACTH levels (332.7 +/- 84.0 pg/ml) were attained 5 min after ether exposure, followed by a rapid decline at 10 min (P less than 0.001) and 20 min (P less than 0.05). Plasma TSH concentrations were unchanged by GAL or saline infusion and were not affected by ether vapor inhalation. To determine the physiological significance of GAL in the control of ACTH and TSH secretion, endogenous GAL was immunoneutralized by the infusion of 3 microliters GAL antiserum (GAL-AS) into the third cerebral ventricle 25 and 1 h before withdrawing blood samples every 15 min for 6 h. Animals treated with normal rabbit serum (NRS) served as controls. Plasma ACTH concentrations were unchanged by NRS during the 6-h period. However, infusion of GAL-AS raised plasma ACTH concentrations to over 400 pg/ml 75 min after infusion in some animals. In general, plasma ACTH concentrations were increased 4 h of the 6-h sampling period compared to levels in NRS-treated controls. In contrast, GAL-AS reduced TSH concentrations by 50% compared to control values. In contrast to these marked actions of centrally administered GAL, ACTH secretion from dispersed anterior pituitary cells in vitro was unaffected by GAL in concentrations up to 10(-6) M. Furthermore, GAL did not alter CRH (1 nM)-induced ACTH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
甘丙肽（GAL）是一种由29个氨基酸组成的肽，可影响几种垂体前叶激素的分泌，包括催乳素（PRL）和生长激素（GH）。由于GAL与血管加压素和促肾上腺皮质激素释放激素（CRH）在下丘脑室旁核（PVN）中共存，我们研究了GAL对自由活动雄性大鼠促肾上腺皮质激素（ACTH）和促甲状腺激素（TSH）分泌的药理和生理作用。将套管通过手术植入成年Sprague-Dawley大鼠的右心房和脑内，分别为脑室内或靠近PVN处。7天后，将GAL（500或1000 ng）或生理盐水注入PVN，并在注入后5、10、20和40分钟采集系列血样。一些动物在PVN注入后还通过吸入乙醚蒸气应激2分钟。生理盐水处理的大鼠基础ACTH浓度增加了2倍；然而，注入GAL后血浆ACTH水平未改变。在将生理盐水注入PVN后，大鼠暴露于乙醚蒸气2分钟，10分钟后血浆ACTH浓度从22.8±6.0 pg/ml增加到596.6±59.9 pg/ml。然而，将GAL注入PVN可减弱应激诱导的ACTH分泌。注入GAL后，乙醚暴露5分钟时达到ACTH峰值水平（332.7±84.0 pg/ml），随后在10分钟（P<0.001）和20分钟（P<0.05）迅速下降。血浆TSH浓度不受GAL或生理盐水注入的影响，也不受乙醚蒸气吸入的影响。为了确定GAL在控制ACTH和TSH分泌中的生理意义，在每15分钟采集一次血样共6小时之前的25分钟和1小时，通过向第三脑室注入3微升GAL抗血清（GAL-AS）对内源性GAL进行免疫中和。用正常兔血清（NRS）处理的动物作为对照。在6小时期间，NRS对血浆ACTH浓度没有影响。然而，在一些动物中，注入GAL-AS后75分钟血浆ACTH浓度升高至400 pg/ml以上。总体而言，与NRS处理的对照相比，在6小时采样期的4小时内血浆ACTH浓度升高。相比之下，GAL-AS使TSH浓度比对照值降低了50%。与中枢给予GAL的这些显著作用相反，体外分散的垂体前叶细胞分泌的ACTH不受浓度高达10^(-6) M的GAL影响。此外，GAL不改变CRH（1 nM）诱导的ACTH分泌。（摘要截短于400字）
