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大鼠妊娠晚期急性应激期间对胎儿神经内分泌系统的性别特异性影响以及酪氨酸同步治疗的作用

Sex-specific effects on the fetal neuroendocrine system during acute stress in late pregnancy of rat and the influence of a simultaneous treatment by tyrosine.

作者信息

Rohde W, Ohkawa T, Götz F, Stahl F, Tönjes R, Takeshita S, Arakawa S, Kambegawa A, Arai K, Okinaga S

机构信息

Institute of Experimental Endocrinology, Humboldt University School of Medicine, Berlin, GDR.

出版信息

Exp Clin Endocrinol. 1989 Sep;94(1-2):23-42. doi: 10.1055/s-0029-1210877.

Abstract

It is well-known that prenatal chronic intermittent stress affects the reproductive system of both sexes. Investigating the effects of an acute maternal stress on the fetal neuroendocrine system, parameters such as hypothalamic catecholamines. CRF, GRF, LH-RH, beta-endorphin, hypophysial beta-endorphin and beta-LPH as well as plasma LH, corticosterone and androstenedione were measured. Pregnant rats of Wistar strain were exposed to restraint stress at day 22 of gestation or to forced immobilization at day 20 of gestation, respectively, and were sacrificed before stress and 10, 30, 60, and 120 min after starting stress. A decrease of fetal hypothalamic catecholamines and an increase of LH-RH content of the hypothalamus as well as of plasma catecholamines were observed under stress on day 22 of gestation. On day 20 of gestation hypothalamic beta-endorphin was depleted in male and unchanged in female fetuses under stress. A depletion of hypothalamic CRF was observed in male fetuses, whereas female fetuses showed an increase of hypothalamic CRF. An increase of GRF was found in fetuses of both sexes. Pituitary opioid content increased in fetuses of both sexes initially, but was depleted secondarily in male fetuses. The LH plasma level was markedly reduced in male, the corticosterone level was elevated in fetuses of both sexes as well as the androstenedione level in female fetuses. A simultaneous treatment of mother animals with tyrosine--a catecholamine precursor--prevented the depletion of hypothalamic and pituitary beta-endorphin as well as in part the reduction of plasma LH levels in male fetuses. Hypothalamic GRF content does not increase under tyrosine treatment in male fetuses, whereas in female fetuses the stress-induced increase of GRF content was rather pronounced under tyrosine than attenuated. These results indicate that fetal hypothalamic neurotransmitters and neurohormones (such as LH-RH, CRF, GRF and opioids) are involved in changing circulating hypophysial and adrenal hormones in fetuses exposed to maternal stress in late pregnancy, whereby sex-specific different pathways might be effective in fetal stress processing. The prenatal administration of tyrosine prevented at least in part--those neurohormonal changes which are affecting the sex-specific brain differentiation.

摘要

众所周知,产前慢性间歇性应激会影响两性的生殖系统。为研究急性母体应激对胎儿神经内分泌系统的影响,对下丘脑儿茶酚胺、促肾上腺皮质激素释放因子(CRF)、生长激素释放因子(GRF)、促黄体生成激素释放激素(LH-RH)、β-内啡肽、垂体β-内啡肽和β-促脂素以及血浆促黄体生成素(LH)、皮质酮和雄烯二酮等参数进行了测量。将Wistar品系的怀孕大鼠分别在妊娠第22天进行束缚应激或在妊娠第20天进行强迫固定,在应激前以及开始应激后10、30、60和120分钟处死大鼠。在妊娠第22天应激时,观察到胎儿下丘脑儿茶酚胺减少,下丘脑LH-RH含量以及血浆儿茶酚胺增加。在妊娠第20天应激时,雄性胎儿下丘脑β-内啡肽减少,雌性胎儿下丘脑β-内啡肽无变化。在雄性胎儿中观察到下丘脑CRF减少,而雌性胎儿下丘脑CRF增加。在两性胎儿中均发现GRF增加。两性胎儿垂体阿片样物质含量最初增加,但随后在雄性胎儿中减少。雄性胎儿血浆LH水平明显降低,两性胎儿皮质酮水平升高,雌性胎儿雄烯二酮水平升高。用酪氨酸(一种儿茶酚胺前体)同时处理母鼠可防止下丘脑和垂体β-内啡肽的减少以及部分防止雄性胎儿血浆LH水平的降低。在酪氨酸处理下,雄性胎儿下丘脑GRF含量不增加,而在雌性胎儿中,酪氨酸处理下应激诱导的GRF含量增加比减弱更为明显。这些结果表明,胎儿下丘脑神经递质和神经激素(如LH-RH、CRF、GRF和阿片样物质)参与了晚期妊娠时暴露于母体应激的胎儿中循环垂体和肾上腺激素的变化,由此性别特异性的不同途径可能在胎儿应激处理中起作用。产前给予酪氨酸至少部分地预防了那些影响性别特异性脑分化的神经激素变化。

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