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雌性幼鼠多巴胺受体的慢性激活:对垂体激素及青春期启动的影响

Chronic activation of dopamine receptors in the female infantile rat: effect on hypophyseal hormones and on the onset of puberty.

作者信息

de Mengido I M, Becú-Villalobos D, Díaz G, Libertun C

机构信息

Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.

出版信息

Endocrinology. 1989 Feb;124(2):746-53. doi: 10.1210/endo-124-2-746.

Abstract

In the female rat the period from days 7-20 of age is special with regard to regulation of hypophyseal hormone secretion. This period is characterized by high FSH levels and the occurrence of sporadic LH peaks. As it has been reported that haloperidol could enhance both gonadotropins at 12 days of age and not at later ages, it was of interest to treat rats during the infantile period with pergolide, a dopaminergic agent of long action, and evaluate its effect on hormone levels and puberty onset. Three different schedules of drug injections were applied: 1) daily injections (0.05 mg/kg.day) on days 1-10, 2) daily injections on days 5-14, and 3) daily injections on days 11-20. It was found that only animals treated with daily injections of pergolide on days 11-20 showed an advance in the age of vaginal opening and first estrus compared to distilled water-injected controls. Thus, the rest of the experiments were performed using injection schedule 3. In this group of animals serum LH and FSH levels were decreased 3 and 6 days after the beginning of pergolide treatment (13 and 16 days of age); at 19 days of age pergolide did not modify gonadotropin levels. One day after the end of pergolide treatment (day 21 of age), there was a rebound in LH levels in drug-injected rats, and a nonsignificant increment in FSH levels was observed. There were no differences in serum gonadotropin levels on days 22, 23, and 25 or peripubertally (29, 33, or 36 days of age). On the other hand, pergolide did not significantly modify PRL levels during the treatment, probably due to the already low values of PRL at these ages. Furthermore, PRL levels were not different between control and pergolide-injected rats at all other ages studied. After puberty onset, animals were observed for eight consecutive cycles, and both groups cycled regularly. Furthermore, PRL and gonadotropins levels were similar at diestrus and proestrus. To evaluate if pergolide treatment during the infantile period had caused permanent alteration in dopamine receptor sensitivity, animals were injected with haloperidol (0.1 or 0.25 mg/kg), and PRL release was evaluated. There were no differences in the hyperprolactinemic effect of the drug between groups. Finally, gonadotropin sensitivity to LHRH was similar in adult female rats in proestrus of both groups. The present results suggest that chronic activation of dopamine receptors during the infantile period evokes specific responses on gonadotropin secretion and advances the age of puberty onset.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

在雌性大鼠中,7至20日龄这段时期在垂体激素分泌调节方面具有特殊性。此时期的特点是促卵泡激素(FSH)水平较高且会出现散发性促黄体生成素(LH)峰值。据报道,氟哌啶醇在12日龄时可增强两种促性腺激素的分泌,而在之后的年龄则无此作用,因此,用长效多巴胺能药物培高利特在幼年期对大鼠进行治疗并评估其对激素水平和青春期启动的影响很有意义。采用了三种不同的药物注射方案:1)在第1至10天每日注射(0.05毫克/千克·天);2)在第5至14天每日注射;3)在第11至20天每日注射。结果发现,只有在第11至20天每日注射培高利特的动物与注射蒸馏水的对照组相比,阴道开口和首次发情的年龄提前。因此,其余实验采用注射方案3进行。在这组动物中,培高利特治疗开始后3天和6天(13和16日龄)血清LH和FSH水平下降;在19日龄时,培高利特未改变促性腺激素水平。培高利特治疗结束后一天(21日龄),注射药物的大鼠LH水平出现反弹,FSH水平有不显著的升高。在第22、23和25天或青春期前后(29、33或36日龄),血清促性腺激素水平无差异。另一方面,培高利特在治疗期间未显著改变催乳素(PRL)水平,可能是因为这些年龄时PRL值本来就低。此外,在所有其他研究年龄,对照组和注射培高利特的大鼠之间PRL水平无差异。青春期启动后,连续观察动物八个周期,两组均正常发情。此外,在动情间期和动情前期,PRL和促性腺激素水平相似。为评估幼年期培高利特治疗是否导致多巴胺受体敏感性发生永久性改变,给动物注射氟哌啶醇(0.1或0.25毫克/千克),并评估PRL释放情况。两组之间该药物的高催乳素血症作用无差异。最后,两组成年雌性大鼠在动情前期对促性腺激素释放激素(LHRH)的敏感性相似。目前的结果表明,幼年期多巴胺受体的慢性激活会引起对促性腺激素分泌的特异性反应,并使青春期启动年龄提前。(摘要截选至400字)

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