长期低剂量γ线照射和照射加电击对老年前期大鼠性激素、肝功能和脂质过氧化物的影响

本文观察了长期低剂量γ射线照射和照射加电击对老年前期(18～21月龄)大鼠血浆性激素水平、肝微粒体混合功能氧化酶(MFO)活力以及组织脂质过氧化物的影响。长期照射加电击使雄性大鼠血浆睾酮水平明显降低(p<0.05),照射与照射加电击均使雄鼠肝微粒体MFO活力明显下降(p<0.05)。长期低剂量γ射线照射和照射加电击组的睾丸自由基浓度较对照组明显升高(p<0.05),长期照射使雄性大鼠肝匀浆与微粒体,睾丸匀浆与线粒体的脂质过氧化物较对照组明显增高,但照射加电击组的脂质过氧化物较照射组(以及对照组)明显下降。实验结果说明照射与照射加电击对老年前期大鼠的作用有所不同,这些环境因素具有加速老化的作用。     

成年去胸腺大鼠和老年大鼠肝微粒体混合功能氧化酶及血浆性激素水平的变化

成年去胸腺(ATx)大鼠和老年大鼠肝微粒体混合功能氧化酶(MFO,包括细胞色素P450、氨基比林-N-脱甲基酶)的活力比成年对照大鼠的低,且降低幅度雄性明显大于雌性。雄性ATx大鼠和老年大鼠血浆睾酮(T)水平降低,雌二醇(E_2)水平增高,E_2/T比值明显增高;雌性ATx大鼠和老年大鼠血浆E_2和T水平均降低,E_2/T比值无明显变化。给雄性ATx大鼠皮下注射丙酸睾丸素可使其肝微粒体MFO活力恢复。提示胸腺对肝脏MFO的影响可能是通过性激素介导的。     

6周自由转轮运动对高脂饲养雄性大鼠性激素及下丘脑-垂体-睾丸轴的影响

目的观察高脂膳食对青春期雄性大鼠下丘脑、垂体、睾丸结构及性激素水平的影响,并探讨6周自由转轮运动的干预效果。方法 3周龄初断乳雄性SD大鼠40只,随机分为普通膳食对照组(C组)、普通膳食运动组(CE组)、高脂膳食组(D组)、高脂膳食运动组(DE组)。C、D组安静饲养8周,CE、ED组在适应性喂养2周后进行6周自由转轮运动,每天上、下午各1 h,每周5 d。8周后,大鼠腹主动脉取血,测血清T、E2、FSH、LH;制备睾丸组织匀浆液测T、E2;制备下丘脑、垂体、睾丸组织切片,光镜下观察其结构变化。结果 (1)与C组比较,D组血清T、E2检出率降低,且睾丸组织中T水平显著降低(P0.05),而血清E2、FSH、LH显著升高(P0.05);下丘脑出现空泡脂滴,垂体中嗜酸性和嗜碱性细胞均减少,睾丸生精小管面积、精子细胞比例和睾丸间质细胞数量降低。(2)与D组相比,DE组大鼠血清T检出值及睾丸T值均增高,而血清E2、FSH、LH显著降低(P0.05);下丘脑组织结构出现空泡脂滴,垂体中嗜酸性细胞数量显著增高,嗜碱性细胞数量无变化,睾丸组织中生精小管面积较高但差异无显著性。结论 6周自由转轮运动可有效改善高脂饲养大鼠导致的性激素分泌异常,雌雄激素比例失衡,但对下丘脑-垂体-睾丸轴的组织结构病理变化改善效果不明显。     

β-内啡肽在雌激素负反馈调节中的作用机理

本文在大鼠的整体实验中,测定了下丘脑和中脑中央灰质的β-内啡肽(β-endorphin,β-EP)和促黄体素释放激素(luteinizing hormone-releasing hormone,LHRH)含量,以研究在雌激素负反馈调节中β-EP和LHRH释放之间的关系。结果表明,体内雌激素水平升高而产生负反馈调节时,下丘脑和中脑中央灰质的β-EP含量明显升高,而下丘脑LHRH的释放受到明显的抑制;纳洛酮阻断β-EP的作用后,下丘脑LHRH释放增加。结果提示,下丘脑和中脑中央灰质β-EP可能同时参与了雌激素对下丘脑LHRH释放的负反馈调节作用。     

心钠素在GABA调节下丘脑正中隆起LHRH释放的介导作用研究

已证明脑神经递质GABA可促进下丘脑正中隆起LHRH神经元末梢的释放功能,这一作用可能通过抑制某些抑制性神经递质或调质释放而实现。本研究旨在观察作为体内循环调节肽的心钠素在大鼠脑内的分布,对LHRH释放的影响及对GABA调节LHRH释放的中介作用。实验结果发现:(1)雄性大鼠不同脑区心钠素的含量不同,其中以下丘脑正中隆起组织含量最高;(2)不同浓度的心钠素(10~(-8)-10~(-6)mol/L)可显著抑制LHRH从下丘脑正中隆起释放,并呈现剂量反应关系。(3)GABA(10~(-6)mol/L组)可显著抑制心钠素的释放;GABA的这一抑制作用可被GABA受体拮抗剂荷包牡丹碱(Bicuculline)完全反转。上述结果提示心钠素参与调节下丘脑正中隆起(ME)LHRH神经元末梢的释放机能,它亦可能介导GABA对下丘脑正中隆起LHRH的调节作用。     

冷适应大鼠脑垂体、下丘脑、脾淋巴细胞和血浆β-内啡肽及其mRNA的变化

本文采用β-内啡肽(β-EP)mRNA打点杂交,反相高效液相色谱和放免测定研究了冷适应SD雄性大鼠垂体、下丘脑、淋巴细胞(LC)和血浆β-EP及其mRNA的变化,结果为:(1)冷暴一周时垂体β-EP mRNA明显增加,从而激活细胞免疫功能。(2)免疫中枢下丘脑和LC β-EP mRNA在冷适应建立(冷暴二周)时增加。(3)血浆β-EP从冷暴二周起持续增加,增强细胞免疫功能。虽然LC和血浆β-EP产物增加,但是垂体β-EP mRNA量从冷暴二周起恢复到对照组水平,很可能是通过LC-垂体-下丘脑轴,信息反馈到中枢神经系统造成的。     

前列腺素与雄性生殖生理

小剂量前列腺素(PGs)作用于下丘脑,增加LHRH释放,后者促使垂体分泌LH、FSH,从而刺激睾酮分泌。睾丸间质细胞的功能还直接受PGs的调节,睾酮也显著影响雄性生殖道中PGs水平。PGs可增加大鼠睾丸重量,刺激生精过程,增加精子细胞数目,提高精子活力,维持生殖道中平滑肌的收缩,参与射精过程,促进精子在雌体生殖道内的运行,故利于受精。大剂量PGs抑制雄性生殖,使血中LH、FSH、睾酮水平下降,使睾丸动脉收缩,导致睾丸萎缩,减少睾丸及副性腺的重量,抑制生精作用,降低附睾精子活力,增加畸精率。     

前列腺素与雄性生殖生理

小剂量前列腺素(PGs)作用于下丘脑,增加LHRH释放,后者促使垂体分泌LH、FSH,从而刺激睾酮分泌。睾丸间质细胞的功能还直接受PGs的调节,睾酮也显著影响雄性生殖道中PGs水平。PGs可增加大鼠睾丸重量,刺激生精过程,增加精子细胞数目,提高精子活力,维持生殖道中平滑肌的收缩,参与射精过程,促进精子在雌体生殖道内的运行,故利于受精。大剂量PGs抑制雄性生殖,使血中LH、FSH、睾酮水平下降,使睾丸动脉收缩,导致睾丸萎缩,减少睾丸及副性腺的重量,抑制生精作用,降低附睾精子活力,增加畸精率。     

雄性大鼠某些机体功能的衰老变化

随着衰老过程雄性 Wistar 大鼠许多系统功能逐渐衰退。与青年鼠相比,中老年大鼠胸-腺明显萎缩。随着衰老,细胞免疫功能、血浆睾酮(T)和雌二醇(E_2)水平、肝微粒体细胞色素 P-450浓度和混合功能氧化酶(MFO)活力均明显衰退。     

Orexin-1受体参与调节老年大鼠异氟醚麻醉苏醒延迟

目的:探索orexin能神经系统是否参与调节老年大鼠异氟醚麻醉觉醒延迟及其具体机制。方法:选择雄性SD大鼠,将其分为老年大鼠组(n=6,20月龄,体重600~800g)和青年大鼠组(n=6,3~4月龄,体重230~250 g)。采用翻正反射恢复时间作为麻醉觉醒时间,记录异氟醚麻醉下老年大鼠和青年大鼠各自的麻醉觉醒时间;通过免疫荧光染色和细胞计数确定老年大鼠和青年大鼠神经元数目,放射免疫法检测两组大鼠血浆orexin-A含量;Western blot检测老年大鼠和青年大鼠orexin-1和-2受体含量。结果:老年大鼠异氟醚麻醉觉醒时间明显长于青年大鼠(P0.05);老年大鼠orexin能神经元的数目与青年大鼠相比差异无统计学意义(P0.05),但其血浆orexin-A含量显著高于青年大鼠(P0.05);老年大鼠orexin-1受体在蛋白质表达中明显低于青年大鼠(P0.05),而orexin-2受体的表达与青年大鼠相比差异无统计学意义(P0.05)。结论:在老龄化过程中,虽然血浆中orexin-A含量代偿性增加,但是由于全脑中orexin-1受体含量的减少,使其并不能充分发挥促觉醒作用,这可能是导致老年人麻醉苏醒延迟的原因之一。     

阉割和睾丸酮替代对雄性老年大鼠下丘脑和血浆促黄体生成...

Hypothalamic and plasma luteinizing hormone-releasing hormone (LHRH) levels following orchidectomy (ORDX) and testosterone (T)-replacement were compared between young (2-3 months old) and aged (24-26 months old) male rats by radioimmunoassay. Plasma T level and hypothalamic LHRH content are markedly decreased in the aged rat as compared to those of the young rat, whereas plasma LHRH levels are similar in the two groups. Following ORDX and ORDX plus T-replacement, plasma T levels in both groups are about the same, whereas the rates of variation of hypothalamic and plasma LHRH levels in the aged rat are significantly lower than those in the young rat. These results suggest that the negative feedback mechanism of the hypothalamic LHRHergic system is impaired in the aged rat, which may be one of the important reasons causing age-dependent deterioration of the functional control of hypothalamic-pituitary-testicular axis.     

Hypothalamic luteinizing hormone-releasing hormone (LHRH) and LH secretion in aging female rats

Age-related changes in hypothalamic luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) secretion were studied in young (6 months), middle-aged (12 months) and old (18 months) female rats. The LHRH levels in the mid-hypothalamic area were higher in intact middle-aged and old females than in young ones. Additionally, there was no age difference in the hypothalamic LHRH levels in male rats. In order to clarify the significance of this age-related increase in female rats, we examined the effects of progesterone treatment in estrogen-primed ovariectomized young and old rats on the LHRH levels in the median eminence (ME) and on plasma LH levels. We found phasic changes in ME-LHRH and plasma LH levels in estrogen-primed rats following progesterone treatment in rats of both ages, but the progesterone-induced change in ME-LHRH levels tended to be delayed in old rats compared with young females. This delay may correspond to the delayed onset, slow and low magnitude of plasma LH increase in old females. The ME-LHRH levels were generally higher in old rats than in young rats. Nevertheless, we found that the increase in plasma LH in response to progesterone treatment in estrogen-primed ovariectomized females was smaller in old rats than young rats. These results suggest that the LHRH secretory mechanism changes with age in female rats. Such alterations may result in the accumulation of LHRH in the mid-hypothalamic area and an increase in ME-LHRH.     

Effects of aging on LH and prolactin after LHRL L-dopa, methyl-dopa, and stress in male rat.

Hypothalamic-pituitary control of prolactin and LH secretion was tested in young (4-6 months) and aged (22-30 months) male Long-Evans rats given L-dopa, methyl dopa, LHRH, or stress treatments. Pretreatment serum LH levels were consistently higher in young than in the aged groups. The increase in serum LH after LHRH injection was only about half as much in aged as compared to young control males. Although acute stress caused a prompt increase in serum LH in young male rats, this treatment was without effect in the aged group. Methyl dopa treatment stimulated serum prolactin secretion in both young and old rats. Although L-dopa treatment caused a reduction in serum prolactin in both age groups, the sensitivity, magnitude, and duration of the reduction was smaller in the aged rats.     

Effects of aging on pituitary and testicular luteinizing hormone-releasing hormone receptors in the rat

Aging exerts profound influences on the function of the hypothalamic-pituitary-testicular-axis. This work has been performed in order to verify whether, in male rats, the decreased secretion of LH and testosterone (T) occurring in old animals is reflected by modifications of luteinizing hormone-releasing hormone (LHRH) receptors at the level of the anterior pituitary and of the testes. To this purpose, the affinity constant (Ka) and the maximal binding capacity (Bmax) for the LHRH analog [D-Ser(tBu)6]des-Gly10-LHRH-N-ethylamide were evaluated, by means of a receptor binding assay, in membrane preparations derived from the anterior pituitary and testicular Leydig cells of male rats of 3 and 19 months of age. Serum levels of LH and T were measured by specific RIAs. The results obtained show that, in aged male rats, the concentration of pituitary LHRH receptors is significantly lower than that found in young animals. On the other hand, the concentration of LHRH binding sites is significantly increased on the membranes of Leydig cells of old rats. In no instance the Ka for the LHRH analog is significantly affected. Serum levels of LH and T are significantly lower in old than in young male rats. In conclusion, these results suggest that the reduced secretion of LH in old male rats may be linked, at least partially, to a decrease of the number of pituitary LHRH receptors. The impaired production of testosterone occurring in aged rats is accompanied by a significant increase of the number of testicular LHRH receptors, indicating that also the intratesticular mechanisms controlling testosterone release undergo significant alterations with aging.     

Functional and morphological changes in the hypothalamo-pituitary-gonadal axis of aged female rats.

Age-related functional and morphological alterations in the hypothalamo-pituitary-gonadal axis were investigated in old recurrently pseudopregnant (RPP) female rats, and these alterations were compared with those in young diestrous rats. LHRH in the median eminence (ME) and mediobasal hypothalamus (MBH) as well as plasma FSH, LH, and progesterone were measured by RIA. LHRH in the lateral ME (LME) and pituitary FSH and LH were evaluated by morphometry and densitometrical immunocytochemistry. Furthermore, by light microscopy, we classified and counted the number of ovarian follicles and corpora lutea. LHRH concentrations in the ME and MBH were similar in old and young rats, whereas in old rats, plasma FSH was markedly increased, LH was moderately increased, and plasma progesterone was unchanged. The number and the total area and immunoreactivity of LHRH-labeled axon cross sections in the LME were reduced in old rats. The number of nucleated FSH-labeled cells and total FSH area and immunoreactivity were almost twice in old compared with young animals. The measurements of LH-labeled cells were not different between the two groups. In old rats, the numbers of ovarian follicles and corpora lutea were reduced and that of atretic follicles increased. In conclusion, age-related morphological impairments of LHRH axons associated with an increased number of FSH gonadotropes and higher plasma FSH in our old RPP rats suggest hypothalamic and pituitary disturbances, which may largely contribute to the complex hormonal disarrangement responsible for the decline of reproductive functions in old female rats.     

Thyroid status in the obese syndrome of rats

The thyroid function was explored by comparing serum total and free iodothyronine levels in young male genetically obese Zucker rats and in their lean littermates, aged from 6 to 8 weeks old. Total and free thyroxine (T4) and 3,5,3'triiodothyronine (T3) levels were significantly decreased in obese rat serum while total 3,3',5'-triiodothyronine (rT3) remained constant. Radioactive T4 half life is slower in the plasma of obese rats. Peripheral synthesis of T3 from deiodination of T4 is also decreased in obese rat liver homogenate. These modifications produce changes in liver mitochondria oxidative phosphorylation and in marker enzyme activity, which are usually associated with hypothyroidism and hypothalamic disturbances. Genetic obesity probably involves activation of peripheral deiodination of T4 to rT3 which induces biochemical and metabolic changes.     

LHRH and LH in peripubertal female rats following prenatal and/or postnatal ethanol exposure

The effects of pre- and postnatal exposure to ethanol (ETOH) on LHRH and LH were investigated. Pregnant and/or lactating dams were fed ETOH during: 1) gestation, 2) lactation, or 3) gestation-lactation. Female offspring were decapitated at 30 or 40 days-of-age; trunk blood was collected for plasma LH RIA; and hypothalamic tissues were collected for LHRH RIA. Hypothalamic LHRH content of all ETOH-exposed groups was less than that of non-ETOH-fed controls at 30 and 40 days-of-age (p less than 0.05). Plasma LH concentrations of all ETOH-exposed groups were less than those of non-ETOH-fed controls at 30 and 40 days-of-age (p less than 0.05). Also, at 30 and 40 days-of-age, the plasma LH concentrations of the animals exposed to ETOH during lactation and gestation-lactation were less than those of the animals exposed to ETOH during gestation (p less than 0.05). These data suggest that ETOH exposure during gestation and/or lactation negatively affects hypothalamic LHRH content of female rat offspring. Decreased hypothalamic LHRH content with corresponding lowered plasma LH concentration suggests that ETOH influences development or maturation of hypothalamic LHRH neurons by possibly decreasing their number or synthesizing capability.     

Effects of ethanol on rat hypothalamic luteinizing hormone releasing hormone. A study utilizing radioimmunoassay

To further understand the mechanism of action by which ethanol (ETOH) decreases plasma luteinizing hormone (LH) levels, the effects of multiple i.p. injections of EOH (1.0--1.5 g/kg) or saline on hypothalamic luteinizing hormone releasing hormone (LHRH) and plasma LH concentrations were evaluated in intact and castrate male rats. After injections, animals were decapitated, brains rapidly removed, and blocks containing the hypothalamus [with median eminence (ME)] were isolated. Hypothalami were subjected to acetic acid extraction and LHRH content quantitated via radioimmunoassay (RIA). Hypothalamic LHRH was found to be inversely correlated with plasma LH. In response to castration, both saline and ETOH-treated rats showed a decrease in hypothalamic LHRH content with a concomitant increase in plasma LH; however, the ETOH-treated animals retained significantly greater concentrations of LHRH and showed significantly lower plasma LH levels when compared to saline-treated controls. Likewise, ETOH-treated intact animals showed significant increases in LHRH content, with LH levels remaining significantly lower than the saline-treated intact controls. Thus, these data from both intact and castrate rats provide evidence to support the hypothesis that alcohol-induced decreases in LH levels are due to a diminished release rate of hypothalamic LHRH.     

Correlation of hypothalamic LHRH, pituitary LH and plasma LH in developing rats.

Hypothalamic LHRH, pituitary LH and plasma LH levels were measured in rats of both sexes from day 5-60 after birth. The content of hypothalamic LHRH was very high in one-week-old male and female rats. It declined gradually till day 17 in the female rat and sharply on day 10 in the male rat. Subsequently the content of hypothalamic LHRH increased and showed peak values on day 25 in the female rat and on day 45 in the male rat. It decreased markedly at respective times of puberty in both sexes (day 37 in the female rat and day 52-60 in the male rat). Results of the study suggest that maturation of hypothalamo-hypophyseal-axis proceeds in three distinct stages. Observations on days 17, 25 and 37 in the female rat and on days 5, 7, 10 and 22 in the male rat clearly show an inverse relationship between hypothalamic LHRH and plasma LH and a parallel relationship between pituitary and plasma LH. Marked decline in the content of hypothalamic LHRH at respective times of puberty in both sexes indicates that the release of threshold levels of LHRH from the hypothalamus may apparently be the event initiating the pubertal changes in rat.     

The effect of luteinizing hormone releasing hormone on the copulatory behavior of hyperprolactinemic male rats

The present study was undertaken to test the hypothesis that the deficits in copulatory behavior observed in hyperprolactinemic male rats may be related to a reduction in hypothalamic release of luteinizing hormone releasing hormone (LHRH). Adult male Fischer 344 rats were made hyperprolactinemic by ectopic pituitary grafts or were sham operated and 30 min prior to being tested for copulatory performance received a single subcutaneous injection of 500 ng LHRH, 100 ng LHRH, or saline. On different occasions, testosterone (T) levels were measured in plasma collected 30 min following identical treatments. Plasma prolactin (PRL) levels were determined in samples collected 30 min after injection of 500 ng LHRH. Pituitary grafting produced the expected, significant increase in plasma PRL levels and significant deficits in copulatory behavior. Treatment of hyperprolactinemic subjects with 500 ng LHRH significantly reduced both the time to first intromission and the time to ejaculation to times comparable with those of sham-operated subjects. The 100-ng dose produced a significant reduction in mount frequency. Plasma T levels were significantly elevated following either dose of LHRH. These results demonstrate that exogenous LHRH can restore normal copulatory performance in hyperprolactinemic male rats and support the hypothesis that a reduction in hypothalamic LHRH release is responsible for the behavioral deficits observed in those animals.