砷暴露人群指甲砷硒含量与砷中毒临床分度关系分析

目的研究砷暴露地区居民饮用水砷浓度与指甲砷、硒含量及砷暴露人群临床分度之间的关系。方法对内蒙古巴彦淖尔市杭锦后旗和五原县不同水砷浓度暴露的599位居民进行指甲采样和临床砷中毒检查。利用电感耦合等离子质谱仪（ICPMS）测定水砷浓度,中子活化分析法（INAA）测定指甲内砷和硒的含量。结果水砷与指甲砷含量呈正相关（r=0.896,P〈0.01）,水砷与指甲硒含量呈负相关（r=-0.322,P〈0.01）,指甲砷与指甲硒含量也呈负相关（r=-0.355,P〈0.01）,指甲砷与砷暴露人群临床分度呈正相关（r=0.225,P〈0.01）。不同浓度砷暴露人群砷中毒临床分度构成不同,差异显著（P〈0.01）。结论砷暴露人群指甲砷与指甲硒呈负相关,提示在人体内砷与硒存在着拮抗效应,且指甲砷含量与砷暴露人群临床分度呈一致趋势,指甲砷对地方性砷中毒的诊断具有重要价值。     

慢性砷暴露对雌鼠卵巢发育的影响

目的通过观察慢性砷暴露昆明种雌鼠卵巢的形态学改变和血清激素雌二醇、孕酮含量变化,探讨砷发挥雌激素效应对卵巢发育的影响及内分泌干扰机理。方法选择暴露于不同浓度As2O3(0、0.05、0.10、0.20、0.40μg/ml)饮水20周的昆明种雌鼠为研究对象,通过HE染色,光镜观察卵巢组织形态变化,采用放射免疫法测定血清激素雌二醇与孕酮含量。结果随着As2O3浓度增加,各剂量组卵巢的卵泡数均有减少趋势,发育异常。血清雌二醇和孕酮含量均有变化。结论慢性砷暴露可造成卵巢组织形态学改变,扰乱血清激素水平,砷具有雌激素效应。     

新疆砷中毒地区水砷和人体尿砷含量的调查

目的了解新疆奎屯地方性砷中毒高砷暴露区与非高砷暴露区水中砷和其他微量元素含量的分布,探讨砷在人体内蓄积排泄情况与水砷的关系。方法采用原子吸收光谱法检测奎屯地方性砷中毒（地砷病）高砷暴露区与非高砷暴露区23份水样中元素含量;选择奎屯129团高砷暴露区83人作为砷暴露组1,29团非高砷暴露区50人作为内对照组,选择123团98人作为外对照组,采用原子吸收光谱法检测各组人群的尿砷含量。结果统计分析表明地砷病高砷暴露区水砷含量明显高于非高砷暴露区（P〈0.05）。高砷暴露区水样中Cu、Pb含量高于非高砷暴露区,Zn含量低于非高砷暴露区（P〈0.05）。砷暴露组尿砷含量明显高于对照组,砷暴露组和内对照组男女尿砷含量无明显差异（P〉0.05）,不同年龄组尿砷含量未见差异（P〉0.05）。结论地砷病高砷暴露区水中Zn含量低,Cu、Pb含量高,可能伴随高砷增加居民患地砷病的危险性;水砷含量与尿砷排泄量之间有一定相关关系。     

饮水砷暴露小鼠肝和脑组织多形态砷检测分析

目的观察饮用含不同质量浓度和不同形态的无机砷(iAsⅢ,iAsⅤ)水,砷化物在小鼠肝和脑组织中的分布及代谢情况。方法小鼠以自由饮水方式暴露iAsⅢ或iAsⅤ42d,采用氢化物发生-超低温捕集-原子吸收分光光度法,测定小鼠肝和脑组织中无机砷(iAs)、一甲基胂(MA)、二甲基胂(DMA)和三甲基胂(TMA)水平。结果在小鼠肝组织中,iAs、MA及DMA均随染砷量的增加而升高;在脑组织中,iAs在各染砷组与对照组之间,差异无统计学意义。DMA在各染砷组中随染砷剂量的增加而升高,但脑组织中未检测到MA。结论经饮水进入小鼠体内的iAsⅢ或iAsⅤ,主要在肝组织内进行甲基化代谢,低质量浓度的iAsⅢ较iAsⅤ更容易进入肝组织,并被甲基化代谢。砷化物可以透过成鼠的血脑屏障,脑组织分布的砷化物形态以DMA为主。     

氟砷暴露致家兔主动脉损伤及系统性炎症反应

目的探讨砷氟单独及联合暴露对家兔动脉组织的损伤作用及其机制。方法 32只新西兰白兔,分为4组,分别给予ddH_2O,50 mg/L氟化钠和(或)13 mg/L三氧化二砷6个月建立中毒模型。采用石蜡切片HE染色进行动脉组织病理学分析;采用ELISA方法检测血清炎症标志物MCP-1和IL-6水平。结果加氟组骨氟浓度显著升高;加砷组血砷、肝脏砷及心脏砷浓度显著升高;联合暴露组同时表现为氟中毒及砷中毒。主动脉病理学结果显示加氟组可见中层弹性膜排列不整齐,疏松;加砷组可见内膜层增厚,内皮下间隙增宽,中层弹性膜排列紊乱、不规则;联合组可见内膜显著增厚,细胞外基质增多,中层弹性膜排列紊乱。氟砷单独及联合暴露组血清MCP-1和IL-6水平升高。结论氟砷单独及联合染毒可引起家兔不同程度的动脉损伤,系统性炎症在氟砷血管毒性的发生中发挥了重要的作用。     

姜黄素干预对慢性饮水砷暴露小鼠肝脏Nrf2信号通路的影响

目的观察姜黄素干预对慢性饮水砷暴露小鼠肝脏核转录因子Nrf2信号通路的影响。方法实验小鼠自由饮用不同浓度亚砷酸钠(NaAsO2,10、50、100 mg/L)6周,再分别给予姜黄素灌胃干预(200 mg/kg和600 mg/kg,每周2次),采用Western blotting和免疫组化技术分别检测肝脏Nrf2、NQO1和HO-1的蛋白表达水平及Nrf2的细胞定位。结果与单纯砷染毒组相比,姜黄素干预组的肝脏Nrf2、NQO1和HO-1蛋白表达均显著增高,同时肝脏细胞的胞浆和胞核中棕褐色阳性颗粒均显著增多,且Nrf2明显入核增多。结论姜黄素干预能诱导饮水砷暴露小鼠肝脏Nrf2蛋白活化,并进一步激活Nrf2下游信号通路。     

吸烟与饮酒对不同浓度饮水型砷暴露人群尿砷代谢模式的影响

目的 探讨吸烟、饮酒对砷暴露人群尿砷代谢的影响.方法 2008年选择山西省高砷地区不同饮水砷浓度暴露的年龄≥18岁的成年人作为调查对象,根据饮水砷浓度将调查对象分为3组:高砷暴露组(饮水砷浓度≥0.05 mg/L),低砷暴露组(0.01 mg/L≤饮水砷浓度＜0.05 mg/L),对照组(饮水砷浓度＜0.01mg/L).排除近期食用过海产品以及有慢性饮水型砷中毒症状的人群,通过问卷调查方式确定吸烟、饮酒的情况,同时采集居民家水样,以及调查对象的即时尿样.采用氢化物发生原子吸收分光光度法检测尿中无机砷(iAs)、一甲基砷(MMA)和二甲基砷(DMA)含量.以iAs、MMA及DMA的总和表示总砷(tAs)水平;以iAs/tAs、MMA/tAs和DMA/tAs分别计算iAs％、MMA％、DMA％;以(MMA+ DMA)/tAs及DMA/(MMA+ DMA)分别计算一甲基化率(FMR)和二甲基化率(SMR)水平.结果 共调查395人,高砷暴露组中烟酒嗜好者MMA％(16.24％)高于无烟酒嗜好者(12.16％),烟酒嗜好者的SMR水平(82.19％)低于无烟酒嗜好者(86.13％),差异有统计学意义(P均＜ 0.05),吸烟者、饮酒者与无烟酒嗜好者相比,各评价指标差异无统计学意义(P＞0.05);在低砷暴露组中吸烟者、烟酒嗜好者的MMA％( 13.86％、13.99％)均高于无烟酒嗜好者(11.83％),吸烟者、烟酒嗜好者的DMA％(72.87％、77.76％)和SMR水平(83.48％、83.90％)均低于无烟酒嗜好者(80.35％、86.54％),差异有统计学意义(P均＜0.05),饮酒者与无烟酒嗜好者相比,各评价指标差异无统计学意义(P＞0.05).对照组人群中吸烟者、烟酒嗜好者的MMA％( 17.27％、17.06％)均高于无烟酒嗜好者(11.52％),吸烟者、烟酒嗜好者的DMA％(73.89％、72.29％)和SMR水平(81.48％、82.58％)均低于无烟酒嗜好者(79.68％、87.19％),差异有统计学意义(P均＜ 0.05),饮酒者与无烟酒嗜好者相比,各评价指标差异无统计学意义(P＞0.05).结论 在不同浓度砷暴露的情况下,吸烟饮酒人群对砷的甲基化能力低于非吸烟饮酒人群.     

长期染砷致家兔肝脏蛋白巯基水平及巯基代谢相关酶活力下降

目的 探讨长期砷暴露对家兔肝脏蛋白巯基水平及与巯基代谢相关酶活力的影响及机制。方法 家兔以自由饮水方式慢性暴露于无机3价砷（iAs^Ⅲ）及5价砷（iAs^Ⅴ），18周后，测定肝脏组织中蛋白巯基、非蛋白巯基、硫氧还蛋白（TRX）水平，以及硫氧还蛋白还原酶（TR）、谷胱甘肽还原酶（GR）活性，同时检测血、尿及毛发中无机砷及其代谢产物甲基砷（MMAs）和二甲基砷（DMAs）。结果 经过18周的砷暴露，两个染毒组血和尿中iAs、MMAs、DMAs以及毛发中iAs、DMAs均显著高于对照组；iAs^Ⅴ组血中iAs、MMAs及尿中MMAs水平显著低于iAs^Ⅲ组，而尿及毛发中iAs水平显著高于iAs^Ⅲ组。iAs^Ⅴ组总巯基及蛋白巯基水平显著低于对照组。iAs^Ⅵ组TRX水平、TR及GR活力以及iAs^Ⅲ组TR活力与对照组相比亦显著下降。结论 家兔长期砷暴露导致肝脏中蛋白巯基水平及与巯基代谢密切相关的TR、GR活力显著下降，提示慢性无机砷暴露会引起肝脏内氧化及抗氧化失衡从而引发组织氧化损伤。     

牛磺酸对砷暴露小鼠肾组织核酸损伤的保护作用

目的 观察牛磺酸对砷暴露小鼠肾组织核酸损伤的保护作用。方法 昆明种小鼠40只，随机分为3组：4mg/L三氧化二砷染毒组、150m异／kg牛磺酸拈抗组以及生理盐水对照组。连续染毒60d，取小鼠肾组织固定，用免疫组织化学方法观察肾组织细胞8-硝基鸟嘌呤（8-NO2-G）的表达。结果 染砷组小鼠肾细胞出现肿胀，胞浆内有空泡变性，部分胞质溶解，核肿胀、溶解等明显的病理学变化。牛磺酸拮抗组小鼠肾组织的病理变化相对较轻。小鼠肾皮质细胞的胞浆中8-NO2-G吸光度值，染砷组（0．043±0．014）明显高于对照组（0．004±0．002），差异有统计学意义（P〈0．01）；牛磺酸拮抗组（0．016±0．013），低于染砷组（P〈0．05），但仍明显高于对照组（P〈0．05）。结论 牛磺酸对砷暴露小鼠肾组织核酸损伤具有保护作用。     

内蒙地砷病病区人群的形态砷暴露研究

对内蒙地砷病病区人群通过饮水而暴露于不同形态砷化合物的种类和水平进行了研究，结果表明，病区饮水中砷主要以无机砷形式存在，其中Ａｓ（Ｖ）水平高于Ａｓ（Ⅲ），有机砷普遍以低浓度水平存在于水中。在该病区开展饮水中不同形态砷暴露水平与地砷病发病关系的横断面流行病学研究所得数据资料，无论单因素分层分析还是多元逐步Ｌｏｇｉｓｔｉｃ回归分析，结果均显示不同形态砷暴露对地砷病的发病有着不同的影响，地砷病的患病率随     

Hormonal modulation of prolyl endopeptidase and dipeptidyl peptidase IV activities in the mouse uterus and ovary.

Prolyl endopeptidase and dipeptidyl peptidase IV are proline-specific peptidases, and are ubiquitously distributed in various tissues in mammals. The specific activities of these peptidases in both uterus and ovary were examined in the SHN strain of mice at estrus or diestrus. A marked change in prolyl endopeptidase activity was found in the uterus and ovary in intact mice during the estrous cycle, the activity being high at estrus and low at diestrus. In ovariectomized mice, prolyl endopeptidase activity was significantly higher in the uterus treated with progesterone or estradiol than in the uterus treated with vehicle oil only or a dopamine antagonist (perphenazine) which stimulates prolactin secretion. On the other hand, notable change in dipeptidyl peptidase IV activity during the estrous cycle was found only in the uterus of intact mice. The activity was low at estrus and high at diestrus. In ovariectomized mice, the uterus exposed to estradiol showed a lower dipeptidyl peptidase IV activity than the uteri treated with progesterone, the dopamine antagonist or vehicle oil. These findings reveal that there is a close correlation between the circulating level of ovarian steroids and the activities of these proline-specific enzymes.     

Role of LH and prostaglandin F2alpha on the development and regression of corpus luteum in mithun (Bos frontalis) estrous cycle

The present investigation was designed to study the role of LH and prostaglandin F2alpha (PGF2alpha) on the development and regression of corpus luteum (CL) in the mithun estrous cycle. Blood samples were collected from jugular vein and PGF2alpha secretion was evaluated on the basis of peripheral 15-keto-13,14-dihydro-PGF2alpha (PGFM) concentration. The daily variations in plasma LH, PGFM, and progesterone (P4) concentrations throughout the estrous cycle were monitored in morning and evening blood samples. The variations in plasma LH, PGFM, and P4 concentrations during the early luteal phase were monitored in blood samples that were collected every 2 h until 120 h following the onset of estrus (Day 0). The pulsatile secretion patterns of plasma LH, PGFM and P4 during estrus (Day 1), mid-diestrus (Day 10), and luteolysis (Day 14) were assessed in blood samples that were collected every 15 min for 6h. In the estrous cycle, P4 concentration increased above basal level on day 6-7, peaked on day 10-12 and declined thereafter. Following estrus, a significant (P<0.01) gradual increase in P4 concentration was observed. LH concentration was found to be significantly (P<0.01) greater around estrus and it declined gradually (P<0.01) following estrus. In the estrous cycle, PGFM concentration increased above basal level on day 9-11, peaked on day 16-17, and declined thereafter. The frequency of LH pulses and basal LH concentration were found to be significantly (P<0.01) greater on day 1, but significantly (P<0.01) greater amplitude of LH pulses was found on day 10 and 14. The frequency of P4 and PGFM pulses was found to be significantly (P<0.01) greater on day 1. In contrast, the amplitude of P4 and PGFM pulses and basal P4 and PGFM concentrations were found to be significantly (P<0.01) greater on day 10 and 14. The results indicate that probably the early stages of CL development continued until day 5-6 of the estrous cycle and a fully functional CL existed approximately at the mid estrous cycle. Luteolysis probably started since day 11-13 of the cycle and completed before the onset of the next estrus. The elevated basal LH concentration along with frequent low amplitude LH pulses were probably required for the early stages of CL development. In contrast, the high amplitude LH pulses of lower frequency during the mid estrous cycle were either sufficient or not required for maintaining the luteal function. Whereas, PGF2alpha pulses of greater amplitude and elevated basal PGF2alpha concentration during the mid and late estrous cycle were probably responsible for luteolysis.     

Variations of liver prolactin receptors during the estrous cycle in normal rats and in the genetically hypoprolactinemic IPL nude rat

Ovine prolactin (oPRL) binding to liver membranes was studied during the estrous cycle in normal and in genetically hypoprolactinemic rats. Serum levels of hormones were measured by radioimmunoassay and prolactin (PRL) binding was determined using 125I-ovine PRL in the 100,000 X g pellet. Scatchard plots obtained were curvilinear throughout the estrous cycle in the normal rat. They were analyzed in reference to the co-operativity model and to the Hill model which give the factor delta and Hill's coefficient (nH), respectively. During the estrous cycle, delta values varied from 3.77 +/- 0.66 on the day of estrous to 13.48 +/- 1.34 on the day of proestrus at 16.00 h. At the same time, nH were 0.97 +/- 0.033 on the day of estrus and 0.72 +/- 0.025 on the day of proestrus at 16.00 h. On the other hand, the number of PRL receptors did not change significantly throughout the estrous cycle. Moreover, the dissociation of 125I-oPRL from its receptor was accelerated by the presence of native ovine oPRL. These results suggest the presence of a negative co-operativity which reached a maximum on the day of proestrus in the normal rat. This co-operativity during the estrous cycle was not found in liver from genetically hypoprolactinemic (IPL nude) rats, which present a total absence of lactation. The delta values did not vary significantly and were 6.52 +/- 1.30 on the day of estrus and 4.41 +/- 0.52 on the day of proestrus at 16.00 h. The difference between the two rat strains was statistically significant on the day of proestrus at 16.00 h for both delta and nH values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proestrous surge of gonadotropin-releasing hormone secretion inhibits apoptosis of anterior pituitary cells in cycling female rats

Estrogen affects apoptotic cell death in estrogen-responsive tissues. The purpose of the present study was to examine dynamic changes in apoptotic cell death in the anterior pituitary gland during the estrous cycle and to investigate neuroendocrine regulation of these changes in cycling female rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) for in situ detection of DNA strand breaks revealed that the number of TUNEL-positive anterior pituitary cells was changing during the estrous cycle, with a maximum in the morning of proestrus and a minimum in the morning of estrus. A similar pattern was observed with Bax immunostaining; however, no difference was observed in Bcl-2 immunostaining. Most of Bax-immunoreactive cells were identified as a subpopulation of gonadotropes. Pentobarbital administered in the afternoon of proestrus attenuated the decrease in TUNEL-positive or Bax-immunoreactive cells in the morning of estrus, although estradiol treatment failed to affect it. This action of pentobarbital was reduced by simultaneous treatment with an ovulation-inducing dose of gonadotropin-releasing hormone (GnRH), but not with progesterone, an ovarian steroid also released after GnRH treatment. These results suggest that anterior pituitary cells, mostly gonadotropes, undergo a cyclic change in apoptotic cell death during the estrous cycle and that the inhibition of apoptosis on estrus is due, at least in part, to the proestrous surge of GnRH secretion.     

The hormonal responses of lipoprotein lipase activity and lipolysis in adipose tissue differ depending on the stage of the estrous cycle in female rats

OBJECTIVE: This study was designed to elucidate whether there were differences in the hormonal responses of the parameters involving triacylglycerol (TG) deposition and mobilization in adipose tissue among the stages of the estrous cycle in female rats. MEASUREMENTS: Adipose tissue was obtained from the parametrial region in female rats at each stage of the estrous cycle. Lipoprotein lipase (LPL) activity in the extracts of acetone/ether powders of the tissues was measured as a parameter for TG deposition. Norepinephrine-stimulated lipolysis in isolated fat cells was measured as a parameter for TG mobilization. RESULTS: LPL activity changed periodically during the estrous cycle; the activity level was highest at diestrus, began to decrease at proestrus, reached a minimum at estrus, began to increase again at metestrus-1, and increased further at metestrus-2. At diestrus and proestrus, LPL activity was increased with an increase in plasma insulin levels, suggesting that plasma insulin was the predominant up-regulator of LPL. But at estrus, metestrus-1 and metestrus-2, LPL activity remained low even when plasma insulin levels were high, indicating that it was not up-regulated by plasma insulin. Norepinephrine-stimulated lipolysis in fat cells was high at estrus and metestrus-1 and low at diestrus. CONCLUSION: The hormonal responses of LPL activity and lipolysis in adipose tissue differed depending on the stage of the estrous cycle.     

Selective regulation of glutamic decarboxylase isoform 65, but not isoform 67, in the bed nucleus of the stria terminalis and the preoptic area of the ewe brain across the estrous cycle.

gamma-Aminobutyric acid neurons in the preoptic area (POA) of the brain may regulate GnRH neurons. The level of expression of two isoforms (65 and 67) of glutamic acid decarboxylase (GAD) in the ewe brain was determined across the estrous cycle by in situ hybridization. GAD mRNA expression (cell number and silver grains/cell) was examined in the subdivisions of the bed nucleus of stria terminalis (BnST), in the diagonal band of Broca, and the POA. The number of cells expressing GAD(65) and GAD(67) mRNA did not change across the cycle. Within the rostro-dorsal BnST, the number of silver grains/cell for GAD(65) mRNA was lower in the follicular phase than the luteal phase or at estrus. In the rostro-lateral division, expression was lower in the follicular phase. In the POA, the number of silver grains/cell for GAD(65) mRNA was lower at estrus than during the luteal phase. The number of silver grains/cell for GAD(67) mRNA did not change across the estrous cycle. GAD(65) is thought to be the active enzyme during periods of high demand of GABA and our results are consistent with the GABA neurons of BnST being most active during the luteal phase of the estrous cycle.     

Estrous Cycle Effects on Operant Responding for Ethanol in Female Rats

Human females have been reported to be uniquely sensitive to the deleterious effects of ethanol, thus it is important to study the characteristics of and mechanisms underlying alcohol consumption that may be specific to females. Models of ethanol self-administration in female rats that take into consideration the estrous cycle have the potential to provide important information concerning these characteristics and mechanisms. The purpose of this study was to explore the effect of the cycle on ethanol self-administration using a limited access operant paradigm. Female Wistar rats were trained to lever press for 10% ethanol versus water using a saccharin fading procedure. Responses were examined across the four phases of the estrous cycle. No effects of estrous cycle phase were observed when these rats were allowed to cycle freely. Subsequently, estrous phase effects were investigated in females whose cycles had been synchronized. Under this condition, an effect of estrous phase was present, with lower ethanol intake observed in estrus (and in some cases proestrus). Synchronized rats all showed at least one very clear 4-day estrous cycle, whereas free-running rats' cycles ranged from 3 to 5 days. Thus, it is more likely that synchronized rats were tested in the identical portion of each phase, when hormone levels were less variable. These results suggest that ethanol may be more reinforcing during diestrus than proestrus and estrus in female rats.     

Distinct pulsatile prolactin secretory patterns during the estrous cycle: possible encoding for diverse physiological responses

PRL levels during the estrous cycle have been reported to be low, with the notable exception of the afternoon proestrous surge. The present study was designed to evaluate the pulsatile pattern of PRL secretion during the low secretory phases of the cycle. Animals were bled at 3-min intervals for 150 min during proestrus morning (AM), estrus AM and evening (PM), metestrus AM, and diestrus AM and PM. Using the algorithm Detect, pulse frequency, duration, interval, peak and trough values, area under the pulses, and mean PRL levels were calculated. PRL secretion was pulsatile during all stages of the estrous cycle, although the pattern varied considerably among the different cycle stages. Pulse frequency was highest during estrus and lowest during diestrus. All quantitative pulse parameters (peak, trough, amplitude, and area under pulse) were also higher during estrus and lowest in diestrus. Analysis of area under the pulse using frequency distribution indicated that at least two subpopulations of pulses, i.e. small mass and large mass pulses, were observed in certain stages of the cycle. Small mass pulses were present at all stages of the cycle; while their frequency remained unchanged, changes in other parameters were observed at different stages which did not always correlate with changes in mean PRL levels. Big mass pulses, on the other hand, presented a clear change in pulse frequency with values rising progressively from diestrus PM through proestrus to peak at estrus. Between estrus PM and metestrus AM these big mass PRL pulses essentially disappeared. In contrast to the marked changes in frequency, big mass PRL pulses were remarkably homogeneous in other quantitative characteristics. The results indicate that distinct changes in PRL pulsatility patterns occur during the estrous cycle; these changes are related to both the pattern and the quality of PRL pulses. Based on the observations of a companion study (28) and other data, we suggest that the genesis of the big mass and small mass PRL pulses involves dopaminergic and nondopaminergic mechanisms, respectively. The timing and selectivity of the changes in PRL pulsatile patterns suggest that those patterns may encode different signals for expression of the diverse actions of PRL on reproductive tissues.     

Changes of prolactin response to dopamine during the rat estrous cycle

The effects of dopamine (DA) on prolactin (PRL) secretion in anterior pituitary tissue from rats selected during various stages of the estrous cycle were analyzed under in vitro conditions. The results were examined in relation to plasma PRL, estradiol and progesterone levels. During the estrous cycle there was a marked variation in the responsiveness of the lactotrophs to the inhibitory action of DA. Rapid changes occurred during proestrus: pituitary lactotrophs were not sensitive to the inhibitory action of 10 nM DA at 15.00 and 17.00 h and were less sensitive to 1 microM DA compared to 09.00 h (p less than 0.01), 12.00 h (p less than 0.05) and 19.00 h (p less than 0.05). This lowest PRL response to DA was associated with the preovulatory PRL surge. The recovery of a higher PRL response at 19.00 h coincided with the decrease of plasma PRL levels. During the remainder of the cycle, plasma PRL levels remained low in estrus, diestrus 1 and diestrus 2. Lactotrophs were sensitive to 1 microM and 10 nM DA during estrus and diestrus 2 but a significant lower PRL response to 1 microM DA (p less than 0.05) and no PRL response to 10 nM DA was observed in diestrus 1. These data show that alterations in the sensitivity of the lactotrophs' responsiveness to DA occur in the anterior pituitary gland during the rat estrous cycle and can lead to the removal of DA inhibition in the presence of physiological DA concentrations. This phenomenon is consistent with the fact that DA could be involved in the preovulatory PRL surge during the estrous cycle.     

Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats

We tested the hypothesis that hindbrain catecholamine (norepinephrine or epinephrine) neurons, in addition to their essential role in glucoprivic feeding, are responsible for suppressing estrous cycles during chronic glucoprivation. Normally cycling female rats were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to monoclonal dopamine beta-hydroxylase antibody (DSAP) into the paraventricular nucleus (PVN) of the hypothalamus to selectively destroy norepinephrine and epinephrine neurons projecting to the PVN. Controls were injected with unconjugated saporin. After recovery, we assessed the lesion effects on estrous cyclicity under basal conditions and found that DSAP did not alter estrous cycle length. Subsequently, we examined effects of chronic 2-deoxy-d-glucose-induced glucoprivation on cycle length. After two normal 4- to 5-d cycles, rats were injected with 2-deoxy-d-glucose (200 mg/kg every 6 h for 72 h) beginning 24 h after detection of estrus. Chronic glucoprivation increased cycle length in seven of eight unconjugated saporin rats but in only one of eight DSAP rats. Immunohistochemical results confirmed loss of dopamine beta-hydroxylase immunoreactivity in PVN. Thus, hindbrain catecholamine neurons with projections to the PVN are required for inhibition of reproductive function during chronic glucose deficit but are not required for normal estrous cyclicity when metabolic fuels are in abundance.