缺碘性甲状腺功能低下大鼠骨发育障碍的病理学观察

目的探讨缺碘所致发育期大鼠甲状腺功能(甲功)低下造成的发育障碍,包括成骨细胞分子异常、骨计量学证据和病理学证据等,本文报告病理学观察结果.方法复制了第1代和第2代碘缺乏大鼠动物模型,测定血清中T3、T4水平,拍摄X光片,并作股骨远端骨切片观察骨发育情况.结果 20日龄正常组与缺碘组T3水平分别为(1.83±1.11)nmol/L和(1.66±1.01)nmol/L,补碘后略有下降,差异无显著意义;T4水平分别为(104.68±25.73)nmol/L和(3.47±1.06)nmol/L,显示甲功低下,补碘后升至(119.88±29.45)nmol/L.缺碘大鼠体重在整个发育过程中(1～84 d)始终低于正常组,平均降低了56%;X光片中可见,缺碘大鼠的长骨较同日龄正常大鼠短且细,骨间隙增大,钙化不良.20日缺碘鼠肌骨远端骨骺病理切片显示,大鼠次级骨化中心形成迟缓且小,骨骺生长中几个软骨细胞区域层次混乱,储备细胞数目减少.增殖区宽度较正常大鼠者减少;甲状腺病理学变化显示,从生后1 d开始,碘缺乏大鼠已经出现了甲状腺肿大的典型变化,包括滤泡体积变小,形状不规则,胶质明显减少或缺如.滤泡上皮细胞增大呈柱状,胞浆淡染,有空泡变性,滤泡间小血管增多,充血明显.生后补碘可以部分纠正上述改变.结论缺碘导致大鼠发育迟缓,体重增长缓慢.骨骼发育不良,长骨骨骺软骨发育障碍,钙化过程也受到影响.生后给缺碘大鼠补碘可以改善骨骼发育.     

碘缺乏对仔鼠大脑烯醇化酶发育的影响

本实验以严重缺碘地区的粮食复制出接近人类的大鼠缺碘模型，用免疫组化方法研究了碘缺乏对仔鼠大脑ＮＳＥ阳性神经细胞发育的影响。结果显示：实验组Ｔ４水平在各日龄都较对照组低，仔鼠大脑从出生至生后３０日龄ＮＳＥ阳性神经细胞发育较对照组落后，ＮＳＥ免疫阳性产物较少，这种差别在海马区、齿状回、皮层更为明显。表明碘缺乏所致甲状腺功能低下是影响脑发育的直接因素，提示甲状腺素是通过影响ＮＳＥ而干扰能量代谢，造成大脑发育障碍。     

不同剂量碘酸钾和碘化钾对缺碘大鼠甲状腺肿回缩效果的影响

目的 观察补充不同剂量和剂型的碘剂对甲状腺肿回缩的效果和甲状腺功能的影响。方法 成功复制缺碘性甲状腺肿(甲肿)动物模型后，分别补给适量(1倍、0．26mg／L)，5倍(1．30mg／L)和50倍(13．00mg/L)于适量碘的碘酸钾和碘化钾3月。结果 各实验组甲状腺相对重量较低碘组明显下降，但均未能恢复至正常水平，且随补碘剂量增加，甲肿恢复呈渐差趋势；各组尿碘排泄情况基本与摄人碘量呈平行关系，各实验组甲状腺组织碘低于正常对照组，且各实验组之间无显著差别；各实验组血清TT4水平显著高于正常对照组，1倍和5倍补碘组甲状腺组织TT4水平明显高于50倍补碘组和正常对照组；相同的补碘水平上，碘酸钾和碘化钾组各项指标均未见显著差异。结论 补碘对甲肿回缩均有一定效果，但适量碘组效果最佳；5倍补碘组甲肿消退虽稍差于适量补碘组，但差别无统计学意义，提示5倍于适量碘仍然是比较安全的；50倍于适量碘组甲肿消退明显减慢，提示过高剂量补碘不利于甲肿回缩；相同的补碘水平上，碘酸钾和碘化钾对甲肿回缩的效果是一致的，证明碘酸钾补碘效果可靠。     

不同碘水平对哺乳期母鼠和仔鼠的甲状腺功能及子代生长发育的影响

目的研究不同碘水平对哺乳期母鼠和仔鼠的甲状腺功能以及子代生长发育的影响。方法Wistar母鼠随机分为4组：重度缺碘组（SID）、轻度缺碘组（MiID）、正常碘组（NI）、碘过量组（ExI）。所有大鼠均食用缺碘饲料,饮水给予不同剂量的碘化钾,喂养3个月后交配,检测哺乳14d时母鼠及其仔鼠的尿碘、乳汁碘和血液甲状腺激素（TH）水平,观察仔鼠的体格发育和神经发育的情况,采用MIAS-2000图像分析系统测量生后10、14、20、25、28日龄仔鼠小脑外颗粒层（EGL）厚度。结果（1）母鼠及仔鼠尿碘、乳汁碘均随饮食碘供给量的增加而增加,其组间变化幅度以母鼠尿碘为最高、仔鼠尿碘次之、乳汁碘最低;（2）SID组母鼠血清TT4、TT3／TT4比值升高,仔鼠TT4降低,与NI组比较有统计学意义,而MiID和ExI组无论母鼠和仔鼠均与NI组无明显差异;（3）SID组仔鼠体格和神经发育明显落后于NI组,小脑EGL增殖和消退明显延迟;MiID和ExI组仔鼠的各项发育指标与NI组无明显差别。结论母亲重度缺碘会严重影响子代的生长发育和神经发育,但在轻度缺碘和碘过量（正常碘的30倍左右）时,通过母体的代偿作用可以保证子代正常的碘营养、甲状腺功能以及生长发育。     

缺碘大鼠的骨发育障碍

目的　研究碘缺乏对大鼠骨发育和骨转换的影响。方法　复制生长发育期碘缺乏大鼠动物模型 ,测定血清中TT3 、TT4、FT4含量 ,对股骨远端 2 /3进行骨计量学测定。结果　碘缺乏大鼠血清TT4、FT4含量显著下降 ,TT3 含量代偿性增加。碘缺乏大鼠骨小梁骨量较正常大鼠明显减少 ,骨小梁体积(TBV) /全部骨组织体积减少约 47% ,TBV/海绵骨体积减少约 3 5 % ,平均骨小梁板厚度减少约 3 6% ,骨小梁表面 /TBV较正常大鼠增加约 3 4% (P <0 .0 1) ,骨皮质平均厚度较正常组减少了 16% (P <0 .0 5 )。碘缺乏大鼠四环素单标记线占全部骨小梁表面的百分比、四环素双标记线占全部骨小梁表面的百分比、平均类骨质宽度、骨小梁类骨质表面占骨小梁表面的百分比、矿化沉积率和组织水平骨形成率均低于正常对照组 (P <0 .0 5或P <0 .0 1) ,矿化延迟时间 (P <0 .0 5 )和类骨质成熟时间 (P <0 .0 1)大于正常大鼠。结论发育期的骨骼对T4的缺乏非常敏感。T4降低时骨骼发育不良 ,骨小梁骨量减少 ,皮质骨的生长也受到影响。碘缺乏组大鼠成骨细胞活性降低和类骨质矿化障碍     

轻、中度碘过量对碘缺乏大鼠甲状腺功能和形态的影响

目的探讨轻、中度碘过量对碘缺乏Wistar大鼠甲状腺功能和形态影响。方法碘缺乏大鼠以饮用1%过氯酸钾溶液制备,分成0μg/L、840μg/L和1680μg/L碘组。双蒸水(DDW)组饲以DDW和普通饲料。固相免疫放射法(IRMA)测定血清TSH,放射免疫法(RIA)测定血清TT3、TT4、rT3和甲状腺组织TT4。光镜、电镜下观察甲状腺形态学变化。图像分析系统测量大鼠滤泡上皮细胞高度和滤泡腔的面积。结果补碘90天时,碘过量组血清TSH明显低于低碘对照组(均P<0.05),但与DDW组相比差异无显著性。1680μg/L碘组血清TT3值明显低于低碘对照组和DDW(均P<0.05),碘过量组血清TT4值明显高于低碘对照组和DDW组(均P<0.001),血清rT3高于低碘对照组和DDW组,但是差异无显著性,碘过量组甲状腺组织TT4含量明显高于低碘对照组和DDW组(均P<0.001)。甲状腺的相对重量均明显高于DDW组和低碘对照组(P<0.001和P<0.05)。碘过量组随着时间延长,滤泡上皮变扁,滤泡周围毛细血管逐渐减少,巨滤泡形成,同时有部分滤泡增生。碘过量组非增生滤泡上皮细胞高度明显小于DDW组和低碘对照组(均P<0.001),1680μg/L碘组泡腔面积明显大于DDW组和低碘对照组(均P<0.001)。结论轻、中度过量碘(尿碘中位数,MUI为300和600μg/L)处理90天,使碘缺乏大鼠甲状腺功能亢进,低碘致甲状腺肿不能完全恢复,甲状腺滤泡异质性增加。     

缺碘对雄性大鼠睾酮以及精子发生的影响

本文采用低碘饲料建立的碘缺乏大鼠模型,观察了碘缺乏对发育期雄性大鼠血浆睾酮及精子发生的影响。结果表明:缺碘所致的大鼠甲低没有影响睾丸的体积和血浆睾酮,实验组和对照组均在45日龄出现精子。这提示:缺碘三个月母鼠所生的第一代仔鼠睾丸发育是正常的。     

锌对缺碘大鼠甲状腺细胞膜脂流动性的影响

目的：观察锌对缺碘大鼠甲状腺细胞膜脂流动性的影响。方法：应用缺碘饲料喂养Wistar大鼠复制缺碘动物模型，同时设补碘，补葡萄糖酸锌和复合锌组，实验中水碘，实验结束时测血清，组织锌含量；以DPH为荧光探剂，荧光偏振法测甲状腺细胞膜荧光偏振度（P）和膜相对流动性（MFU）。结果：缺碘组尿碘降低，加碘组和两组加锌组尿碘，组织锌升高，缺碘组甲状腺细胞膜脂P值升高，MFU降低；加碘组P值和MFU基本达到对照组水平，两组加锌组较缺碘组P值降低，MFU升高，结论：缺碘大鼠甲状腺细胞膜脂流动性降低，补锌可拮抗缺碘所致甲状腺细胞膜损伤，但作用不及补碘显著。     

中轻度过量补碘对非碘缺乏大鼠甲状腺功能和形态的影响

目的 研究中轻度过量补碘对非碘缺乏Wistar大鼠甲状腺功能和形态的影响。方法 将Wistas大鼠随机分为双蒸馏水(DDW)、3倍碘、6倍碘、10倍碘、20倍碘5组,每组10只。固相免疫放射分析法(IRMA)测大鼠血清促甲状腺激素(TSH),放射免疫分析法(RIA)测血清总T4(TT4)、总T3(TT3)、反T3(rT3)和甲状腺内TT4。砷铈分光光度法测定尿碘。光、电镜下观察,图像分析仪测量滤泡上皮细胞高度和滤泡腔面积。结果 与DDW组比较,补充3倍以上碘各组90d时血清TSH值增高,但差异无显著性;血清TT3明显降低(P=0．0001),TT4明显增高(P=0．001),组织TT4也明显增高(P=0．0001),血清rT3值无明显差异;滤泡腔面积增大,上皮细胞变扁,胞核染色深,滤泡融合破裂,巨滤泡形成,毛细血管减少;上皮细胞内质网扩张,次级溶酶体增多,微绒毛减少,染色体浓集。结论 补充3倍以上碘使非碘缺乏大鼠出现甲状腺功能减退倾向,抑制和破坏大部分甲状腺滤泡上皮细胞。     

缺碘对发育期大鼠甲状腺激素水平的影响

SegaI等于1982年报道，大鼠血清T3和T4含量在出生时都是最低，生后1～2个月达到最高峰。以后随年龄的增长。血清T3降低或不变，血清T4降低。冯力等于1991年测定了2,6,12，18月龄大鼠血清TT3水平。发现TT3水平在2月龄时最高，以后随年龄的增加而逐渐下降。我们在复制胚胎期和生后发育期碘缺乏大鼠动物模型以研究碘     

Increased rat femur osteocalcin mRNA concentrations following in vivo administration of thyroid hormone.

Thyroid hormone has a direct resorptive effect on bone. Thyroid hormone therapy in doses that suppress pituitary TSH production result in a reduction in bone density. Osteocalcin is a bone matrix protein. Serum levels are a sensitive marker for bone turnover and are increased in hyperthyroid patients. In order to establish an animal model to study the effects of thyroid hormone on bone turnover, we measured rat femur osteocalcin mRNA following in vivo administration of thyroid hormone. Young CD rats weighing 60-90 g were given daily ip injections of T3, T4, or saline (control) for 12 days. Blood was obtained for radioimmunoassays, and RNA was extracted from femurs and analyzed by Northern blot using a 60-mer synthetic oligonucleotide probe corresponding to bases 360-420 of rat osteocalcin mRNA, labeled with [32P] ATP by 5'-end-labeling. Serum TSH concentrations were suppressed to subnormal levels by the lowest doses of T3 and T4, and to undetectable levels by the higher doses. Increases in serum T3 and T4 concentrations were proportional to the dose of each administered hormone. T3, 5 and 10 micrograms/100 g body weight, resulted in a 43% and 62% increase in osteocalcin mRNA, respectively. T4, 5, 10, and 20 micrograms/100 g body weight, resulted in a 35%, 47%, and 135% increase in osteocalcin mRNA, respectively. These data demonstrate that in vivo administration of either T4 or T3 to young rats results in a significant dose-dependent increase in femur osteocalcin mRNA concentrations.     

T-2毒素在正常和低营养状态下对大鼠膝关节骺板及干骺端骨组织生长发育的影响

目的 观察T-2毒素在正常与低营养状态下对大鼠膝关节骺板及股骨、胫骨干骺端骨组织生长发育的影响,为探讨大骨节病的可能致病因素及早期干预治疗提供实验依据.方法 3周龄Wistar大鼠90只,雌雄各半,体质量60～70 g,将大鼠按体质量、性别随机分为3组:对照组(普通饲料喂养)、T-2毒素+普通饲料组、T-2毒素+低营养饲料组,每组30只.T-2毒素1.0 mg/kg,每周5次,灌胃给药,连续4周.观察大鼠毛发、活动度、体质量变化.在第1、2、4周后,取左侧膝关节骺软骨和股骨、胫骨干骺端(股骨远端、胫骨近端),HE和Masson染色后,光镜下观察大鼠骺板软骨细胞形态和骺板基质中胶原的含量;应用Image-Pro Plus 6.0软件,分析胫骨干骺端骨小梁体积分数.结果 对照组大鼠毛发色泽光亮,活动良好,T-2毒素+普通饲料组及T-2毒素+低营养饲料组大鼠毛发色泽暗,活动减少.对照组、T-2毒+普通饲料组、T-2毒素+低营养饲料组大鼠在第1、2、4周的体质量分别为[(81.0±6.2)、(79.0±5.1)、(77.0±7.5)g],[(101.8±6.7)、(97.0±6.8)、(93.0±53)g],[(151.1±15.7)、(126.5±11.9)、(106.5±11.5)g];体质量在第2、4周组间比较差异有统计学意义(F值分别为9.72、41.65,P均＜0.05),其中第4周组间两两比较差异有统计学意义(P均＜0.01).光镜下,在第2周,T-2毒素+普通饲料组、T-2毒素+低营养饲料组大鼠骺板肥大带软骨细胞出现骺软骨细胞坏死;在第4周,细胞坏死程度加重,其中T-2毒素+低营养饲料组细胞坏死较为明显.T-2毒素+低营养饲料组大鼠骺板基质中胶原着色明显变淡,表明基质中胶原含量明显减少.图像分析显示,大鼠胫骨干骺端骨小梁体积分数在第2、4周,组间比较差异有统计学意义(F值分别为5.4、29.6,P＜0.05);其中T-2毒素+低营养饲料组[(0.55±0.12)%、(0.21±0.08)%]与对照组[(0.67±0.09)%、(0.51±0.14)%]比较差异有统计学意义(P均＜0.01).结论 在正常营养状态下,T-2毒素可导致大鼠骺板软骨肥大层细胞坏死,骺板胶原含量降低,干骺端骨小梁形成障碍;在低营养状态下,T-2毒素可导致大鼠骺板细胞坏死和于骺端成骨障碍更为显著,但这种表现是否与大骨节病的发生有关,还有待研究.     

Simulated weightlessness-induced attenuation of testosterone production may be responsible for bone loss

This study examined the effects of simulated weightlessness on serum hormone levels and their relationship to bone mineral density (BMD). The tail-suspended (i.e., hindlimb suspended, HLS) rat model was used to simulate weightless conditions through hindlimb unloading to assess changes in hormonal profile and the associated bone loss. In the first study, 24 adult male rats were assigned to two groups with 12 rats being HLS for 12 d, and the remaining 12 rats serving as ground controls. On d 0, 6, and 12, blood samples were taken to estimate circulating hormone levels. HLS rats had significant reductions in testosterone, 1,25 (OH)2 vitamin D, and thyroxine levels by d 6 (p<0.01); their testosterone levels were almost undetectable by d 12 (p<0.001). Serum cortisol levels in these rats were elevated on d 6 (p<0.02), but returned to normal levels by d 12. No changes were observed with serum ionized calcium and other hormones examined, as well as the body weights, and weights of thymus, heart, and brain. In the second study, eight rats were ground controls, while an additional eight rats were HLS for 12 d before being removed from tail-suspension and maintained for a further 30 d. Blood samples were collected every 6th d for 42 d. This study showed that both serum thyroxine and 1,25(OH)2 vitamin D levels returned to normal levels soon after hind limb unweighting, while serum testosterone levels matched normal levels only after a further 3-4 wk. These studies showed a significant decrease of femur weights, but not weights of humeri in HLS rats suggesting that this is a specific effect on unloaded bones. On d 12 in both studies, a significant reduction in the lumbar spine (p<0.05) and the femoral neck (p<0.01) BMD appeared in HLS rats. This was confirmed in the second study, where HLS led to a significant decrease in BMD even extending to d 42. Previous studies have shown that space flight and tail-suspension lead to marked reductions in bone formation with little effect on bone resorption. Recently, we reported that androgen replacement can indeed prevent bone losses in this animal model. Therefore, it seems logical to propose that the significant decreases of serum testosterone observed in these tail-suspended animals are, at least in part, responsible for the losses of BMD seen in their affected weight-bearing bones (i.e., lumbar spine and the femur). Considering that 1. testosterone is anabolic to osteoblasts and also decreases the rate of bone turnover 2. serum testosterone levels are markedly suppressed in simulated weightlessness, and 3. testosterone replacement therapy prevented the bone loss in HLS rats, we propose that the testosterone deficiency in this animal model is related to their bone loss.     

Skeletal growth of fetuses from streptozotocin diabetic rat mothers: in vivo and in vitro studies

Summary For largely unknown reasons severe or moderate diabetes of pregnant rats results in pronounced fetal growth retardation. Therefore, some skeletal growth parameters of fetal rats from streptozotocin diabetic mothers were studied in vivo and in vitro. Two days post conception rats were intravenously injected with 65 mg/kg body weight streptozotocin. On day 20 post conception 8 normal and 8 diabetic rat mothers received 5 Ci 3-H thymidine intraperitoneally. One day later the experiments were terminated. Fetal body weight and body length were significantly (p<0.05–0.001) reduced in the hyperglycaemic rats compared to normal rats, as was the thymidine incorporation into rib cartilage (p<0.02). In the cell culture colony formation from isolated chondrocytes of normal and hyperglycaemic fetuses was determined. Proinsulin, insulin (62.5–250 ng/ml), insulin-like growth factor I and II (6.25–25 ng/ml) significantly (p<0.05–0.001) augmented colony formation in a dose-dependent manner, with the somatomedins being 8 times more effective than proinsulin or insulin. Isolated chondrocytes from hyperglycaemic compared to normal fetuses formed significantly (p<0.05–0.001) fewer colonies in the basal state and in response to all 4 hormones. The results confirm the growth retardation of fetuses from diabetic rat mothers. A reduced responsiveness of chondrocytes from hyperglycaemic fetuses to various growth factors could be demonstrated as compared to cells from normal fetuses.     

Cerebral hypothyroidism in rats with adult-onset iodine deficiency

Rats fed chronically a low iodine diet may have low serum T4 and high circulating TSH, despite normal serum T3. As the brain depends to a great extent on intracellular generation of T3 from T4 for its total and nuclear T3, we have carried out two experiments to determine whether the brain of iodine-deficient rats may become hypothyroid, despite normal serum T3 levels. In both experiments we confirmed previous data, showing that the pituitary and liver of iodine-deficient rats with very low plasma T4 levels are hypothyroid as compared to those of animals receiving the same diet supplemented with KI, though not as markedly as animals which had undetectable circulating levels of both T4 and T3 as a consequence of chronic ingestion of KC1O-4, or of surgical thyroidectomy. We have further found that the nuclear T3 content was decreased in the brain of iodine-deficient rats, as compared with the animals on the iodine-supplemented diet. The nuclear to plasma ratios of labeled T3 showed that the uptake of this hormone into liver and brain nuclei is not decreased in the iodine-deficient rats as compared with those on the iodine-supplemented diet. This finding indicates that the decreased liver and brain nuclear T3 contents of iodine-deficient rats are likely to be a consequence of the marked reduction of their T4 pool, leading to decreased amounts of intracellularly generated T3. The number of spines on shafts of pyramidal neurons from the visual cortex of iodine-deficient rats was lower than that of rats fed the same diet supplemented with KI. Their distributions along the shaft were also not the same. Such changes might well be an index of cerebral hypothyroidism, as they are similar to those found after thyroidectomy of adult rats. It is concluded from the present findings that normal circulating T3 levels may not be sufficient to maintain brain euthyroidism in rats fed a diet iodine deficient enough to result in very low circulating T4 levels.     

缺碘大鼠补碘对脑内甲状腺激素受体的影响

目的研究缺碘大鼠补充不同质量浓度碘后脑内甲状腺激素受体与激素结合动力学参数的变化。方法复制Wistar低碘大鼠,然后根据饮用不同质量浓度的碘水来分组。选用第2代20日龄仔鼠实验,测定甲状腺功能状态,利用放射配体结合分析法测定脑内T3受体。结果①血清T3浓度:低碘组(LI)、高碘组(HI)、适碘组(AI)与正常对照组(N)相比,差异无显著意义(P> 0.05)。血清FT3:LI组、HI组明显高于N组(P< 0.05);②血清T4和FT4:LI组和HI组均显著低于N组(P< 0.05);③受体最大结合容量(MBC):LI组明显高于N组(P< 0.05)。结论LI组血中TT4和FT4低于N组,而脑中T3核受体MBC高于N组,提示甲状腺功能低下(甲低)状态下,脑组织中T3核受体有代偿性升高。高碘状态下缺碘大鼠脑细胞核T3核受体、MBC虽略有升高,但血中TT4和FT4却低于正常,提示长期缺碘后过量补碘会出现碘性甲低。长期缺碘后,即使补充适量碘也会出现一过性碘性甲状腺功能亢进(甲亢)。     

Hypothyroidism in severely iodine-deficient rats

The thyroid status of severely iodine-deficient rats was assessed by measurement of the resting metabolic rate (RMR) and liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). Rats maintained on the iodine-deficient diet for 2 or 3 months showed significantly reduced RMR and alpha-GPD, compared to rats on the same diet supplemented with KI in the drinking water. They also displayed markedly reduced serum T4 levels, slightly reduced serum T3 levels, and highly elevated serum TSH levels. A significant decrease in liver alpha-GPD was observed 29 days after the rats were placed in iodine-deficient diet. However, the decrease in RMR in the same animals was not statistically significant. These results suggest that measurement of liver alpha-GPD may be a more sensitive index of impending hypothyroidism than measurement of O2 consumption. The present study demonstrates that a hypothyroid state can be induced in rats exposed to a severely iodine-deficient diet. In severe iodine deficiency, the compensatory mechanisms of increased TSH stimulation and preferential T3 secretion from the thyroid are insufficient to prevent a fall in serum T3. The hypothyroid state results from the inability to maintain a normal serum T3 level and possibly also from the very low levels of serum T4.     

Ethanol-induced Changes in Morphology and Strength of Femurs of Rats

Chronic ingestion of ethanol resulted in ultrastructural and mechanical changes in rat femurs. Scanning electron microscopy of the distal end of the femur revealed that the trabeculae of bones from ethanol-fed rats were thinner, more columnar, and more extensive than those from control rats. Three-point bending tests of the rat femurs showed that the maximum force or so-called "strength" required to break the bone was less in ethanol- than in control-fed animals. A significant inverse correlation was observed between the strength required to break the femur and the dose of ethanol calculated on a body weight basis. For the first time our study presents quantitative proof that a relationship exists between bone strength and the consumption of ethanol in rats. The study revealed that ethanol consumption resulted in a weaker femur compared to controls. We suggest that a common mechanism may be responsible for the decreased bone strength of ethanol-fed rats and the increased incidence of fractures in human alcoholics.     

The molecular actions of thyroid hormone in bone.

Thyroid hormone (T(3)) is essential for the normal development of endochondral and intramembranous bone and plays an important role in the linear growth and maintenance of bone mass. Childhood T(3) deficiency results in retardation of skeletal development and growth arrest, whereas T(3) excess leads to accelerated growth and bone formation. In adult thyrotoxicosis, there is increased bone remodelling, characterized by an imbalance between bone resorption and formation, which results in net bone loss and an increased risk for posteoporotic fracture. These clinical observations demonstrate the importance of T(3) in skeletal development and metabolism. Nevertheless, the molecular mechanisms of T(3) action in bone are poorly understood. Here, we provide an overview of T(3) regulation of chondrocytes, osteoblasts and osteoclasts, and the actions of thyroid hormone receptor (TR) isoforms in skeletal development. The possible roles of T(3) and TRs in nuclear receptor crosstalk, prereceptor ligand metabolism, heparan sulfate proteoglycan synthesis and angiogenesis are also considered.