Androgen-sensitive changes in regulation of restraint-induced adrenocorticotropin secretion between early and late puberty in male rats

Androgen-sensitive changes in regulation of restraint-induced adrenocorticotropin secretion between early and late puberty in male rats
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DOI:
10.1210/en.2003-0565
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发表时间:
2004-01-01
期刊:
影响因子:
4.8
通讯作者:
Dallman, MF
Dallman, MF
中科院分区:
医学2区
文献类型:
--
作者:
Gomez, F;Manalo, S;Dallman, MF

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雄性大鼠青春期早期(40d)和晚期(60d)ACTH分泌的调节变化。我们测试了这种情况是否因为睾丸激素对大脑的激活作用而发生。我们测量了肾上腺切除、皮质酮替代的大鼠进入和离开青春期时,在接受或不接受非类固醇雄激素受体拮抗剂氟他胺治疗的情况下,睾酮和ACTH对反复束缚的反应。氟他胺可增加睾酮水平。40d时ACTH反应较强,氟他胺对ACTH反应有抑制作用,60d时ACTH反应较低,而氟他胺使ACTH反应增强。在d4,在室旁内侧核(MpPVN)和杏仁内侧核,基础精氨酸加压素(AVP)mRNA在束缚后增加,而在终纹床核则随年龄增加而增加。计数AVP免疫反应阳性(AVP-ir)和促肾上腺皮质激素释放因子(CRF)阳性神经元的数量。杏仁内侧核AVP+细胞无明显变化。束缚后40d中央核CRF+细胞减少,60d增加,40d氟他胺不影响束缚反应,60d阻断束缚诱导的CRF+细胞增加,束缚后40d终纹床核与mpPVN CRF-ir呈负相关,60d与mpPVN AVP-ir呈负相关,PVN对CRF+细胞无影响。然而,AVP+细胞仅在束缚+氟他胺组在40d时增加,在束缚+氟他胺组在60d时趋于增加。我们得出结论:在青春期,睾酮诱导在决定自主神经、神经内分泌和行为对慢性应激反应的通路中神经肽的调节发生显著变化。
Regulation of ACTH secretion changes between early (40 d) and late (60 d) puberty in male rats. We tested whether this occurs because of activating effects of testosterone on the brain. We measured testosterone and ACTH responses to repeated restraint in adrenalectomized, corticosterone-replaced rats entering and leaving puberty with or without treatment with flutamide, a nonsteroidal androgen-receptor antagonist. Flutamide increased testosterone. ACTH responses were high and suppressed by flutamide at 40 d. At 60 d, ACTH responses were low and increased by flutamide. On d 4, basal arginine vasopressin (AVP) mRNA was increased by restraint, but not age, in the medial parvicellular paraventricular nucleus (mpPVN) and medial amygdala and increased with age in the bed nucleus of the stria terminalis. We counted numbers of AVP-immunoreactive (AVP-ir) and corticotropin-releasing factor (CRF)-ir neurons. In medial amygdala, there was no change in AVP+ cells. With restraint, CRF+ cells in the central nucleus decreased at 40 d and increased at 60 d. Flutamide did not affect the response at 40 d but blocked restraint-induced increases at 60 d. After restraint, the bed nucleus of the stria terminalis AVP-ir correlated negatively with mpPVN CRF-ir at 40 d and with mpPVN AVP-ir at 60 d. In PVN, there were no effects on CRF+ cells. However, AVP+ cells increased only with restraint plus flutamide at 40 d and tended to increase with restraint and decrease with restraint plus flutamide at 60 d. We conclude that during puberty testosterone induces marked changes in regulation of neuropeptides in pathways known to determine autonomic, neuroendocrine, and behavioral responses to chronic stress.