葛根素对去卵巢大鼠骨质疏松和血脂的作用

激素替代疗法（HRT）对绝经后骨质疏松防治效果肯定，但HRT使心血管疾病发生的相对风险增加22％，对脂代谢影响尚无定论，长期应用可引起子宫内膜癌和乳腺癌。一些植物雌激素具有选择性雌激素受体调节功能，与合成雌激素有相似的抗绝经后骨质疏松作用。葛根素属植物雌激素，有扩张血管、改善心脑供血和抗动脉粥样硬化的作用。近年的研究表明，葛根异黄酮可降低去卵巢大鼠肝内胆固醇（TC）和甘油三酯（TG）水平，体外研究提示葛根素有抑制骨吸收的作用，但葛根素对去卵巢大鼠骨质疏松和血脂代谢的系统研究报道较少。我们对去卵巢大鼠模型给予葛根素，观察骨质疏松大鼠骨密度、骨生物力学指标和血脂的变化。     

雌、雄激素对雄性大鼠血脂代谢及肝血脂代谢相关酶的影响

目的探讨雌、雄性激素对雄性大鼠血脂代谢和肝血脂代谢相关酶的影响。方法24只雄性SD大鼠(320±20)g随机分为去势对照组(ORX组)、去势二氢睾酮(DHT)(DHT组)、去势雌二醇组(E2)(E2组)和正常对照组(对照组),每组6只。ORX组、DHT组、E2组行去势手术,对照组进行假手术。DHT组皮下注射DHT溶液(0.6mg.kg-1.d-1,医用玉米油为溶剂),E2组皮下注射E2(0.2mg.kg-1.d-1,医用玉米油为溶剂);对照组、ORX组注射医用玉米油(安慰剂)。各组动物饲喂高胆固醇高脂肪饮食,于14w后处死全部实验动物,酶法测定各类脂蛋白胆固醇及血脂等指标;酶免法(ELISA)测定血浆DHT浓度,放免法检测血浆睾酮(T)、E2水平。称量各组动物的体重和肝脏湿重,取肝脏组织处理,测定血脂相关代谢酶。结果血浆T浓度DHT组、ORX组和E2组显著低于对照组(P<0.05);DHT水平DHT组和对照组两组间无统计学差异(P>0.05)。血浆E2水平,E2组显著高于DHT组、ORX组、对照组(P<0.05),DHT组与ORX组组间无统计学差异(P>0.05)。E2组血浆TC明显高于ORX组、DHT组和对照组(P<0.05);ORX组高于DHT组、对照组(P<0.05),但DHT组与对照组间无统计学差异(P>0.05);E2、DHT组血浆TG明显高于对照组(P<0.05);ORX组与对照组无统计学差异(P>0.05);ORX组、E2组血浆HDL-C明显高于DHT组、对照组(P<0.05);DHT组与对照组无统计学差异(P>0.05);E2组血浆HDL-C高于DHT组、ORX组与对照组,但DHT组、ORX组与对照组各组间均无统计学差异(P>0.05)。肝脏HL、LPL、CY7PA1mRNA表达DHT组高于E2组、ORX组与对照组,E2组低于ORX组与对照组(P<0.05)。结论雌激素降低雄性大鼠肝脏HL、LPL、CY7PA1活性,雄激素激活HL、LPL、CY7PA1的表达;雄、雌激素都影响血脂代谢,DHT可导致TC降低,同时伴有TG升高;而E2使TC、LDL升高。     

Antifertility effects of estradiol in adult male rats.

The dose-related effects of estradiol 17-beta at the doses 0.1 pg, 10 microg, 100 microg, 200 microg, 300 microg, 400 microg, 1,000 microg/kg/day were determined on sperm motility, potency, fertility parameters, serum levels of LH, FSH, PRL and testosterone, weights of testes and accessory sex organs, weights of pituitary and adrenal glands. The drug was administered daily via sc route for a period of 60 days. Dose-related effects on fertility parameters of the estradiol-treated male rats were ascertained by allowing them to mate with normal cycling female rats. Estradiol at 0.1 microg/kg/day dose significantly reduced sperm motility with no effects seen on potency or fecundity, serum LH, FSH, PRL or testosterone, weights of testes and accessory sex organs while pituitary weight increased. Estradiol at 10 microg/kg/day dose significantly reduced motility, serum LH, FSH, weights of testes and accessory sex organs, while pituitary weight increased with no effects seen on potency, fecundity, PRL or testosterone. Estradiol at 100-1,000 microg/kg/day dose significantly reduced motility, potency and fecundity, serum LH, FSH and testosterone, weights of testes and accessory sex organs while serum PRL and the weights of pituitary and adrenal glands increased significantly. Histology of the testes revealed disorganization of the cytoarchitecture in the seminiferous tubules, vacuolation, absence of lumen and compartmentalization of spermatogenesis. Estradiol withdrawal, testosterone propionate at 100 pg/kg/day or antiestrogen (tamoxifen citrate) at 400 microg/kg/day prevented the histological changes. It is conduded that estradiol reduces sperm motility even at a low dose. Low doses (<10 microg/kg/ day) appear to maintain whilst high doses (>10 microg/kg/day) reversibly disrupt spermatogenesis. Prevention of disruption by testosterone or antiestrogen indicates crosstalk between androgen and estrogen receptors in Sertoli cells. Loss of potency and fecundity also suggests effects on crosstalk between these receptors in other male reproductive organs.     

Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency.

Both short and long term effects of androgen deficiency and steroid replacement therapy on skeletal homeostasis were investigated in aged (13-month-old) male rats. The animals were either sham operated (n = 28) or orchidectomized (orch; n = 89). The orch animals were divided into 5 groups; 26 rats received an empty sc Silastic implant (orch), all others received an implant containing testosterone (T), 5 alpha-dihydrotestosterone (DHT), 17 beta-estradiol (E2), or nandrolone (Nandro; 15-16 rats in each group). Half of the rats were killed 1 month (short term experiment) after implantation; the others were killed 4 months after implantation (long term experiment). Short term androgen deficiency caused a significant increase in both serum osteocalcin and histomorphometric parameters of bone turnover measured at the proximal tibial metaphysis, but not in a significant decrease in bone mass at this site. This increase in bone turnover was prevented not only by T and DHT, but also by E2 and Nandro. Long term androgen deficiency resulted in a decrease in the calcium content of both tibia and lumbar vertebrae. Cancellous bone volume in the proximal tibial metaphysis was +/- 50% lower in the orch group (P less than 0.001) 4 months after orchidectomy. At the same time, cortical bone was lost in orch rats; femoral cortical thickness was reduced by 12% (P less than 0.01), and cortical density tended to be lower. T, DHT, E2, or Nandro treatment completely prevented this decrease in cortical thickness and density. T and Nandro were also able to prevent the cancellous bone loss. DHT could only partly prevent cancellous bone loss. E2 treatment resulted not only in a sustained decrease in both serum osteocalcin concentrations and histomorphometric indices of bone turnover, but also in a net gain of cancellous bone volume (P less than 0.05 vs. sham). No significant differences in serum concentrations of vitamin D metabolites or nephrogenous cAMP were observed between groups in both short and long term experiments. We conclude that bone mass in aged male rats was significantly decreased 4 months after orchidectomy, preceded by an early increase in bone turnover. Both the early increase in bone turnover and the later decrease in bone mass were prevented by aromatizable and nonaromatizable androgens by estrogen and by nandralone.     

二氢睾酮对大鼠血脂代谢及肝细胞脂肪沉积影响的实验研究

目的探讨雄激素二氢睾酮(DHT)对雄性大鼠血脂代谢和肝细胞脂肪沉积的影响。方法24只SD雄性大鼠,随机分为去势对照组(ORX)、去势低剂量二氢睾酮(LD-DHT)、去势高剂量组(HD-DHT)和正常对照组(INT),每组6只。LD-DHT组和HD-DHT组皮下注射不同剂量DHT溶液,正常对照组、ORX组注射医用玉米油(安慰剂)。各组动物饲喂高胆固醇高脂肪饮食,14w后处死,CHO-PAP法测血脂;ELISA法测血清DHT浓度,放免法检测血清睾酮。称量各组动物的体重和肝脏湿重,取肝脏组织了解肝脂肪变情况。结果ORX组、LD-DHT组、HD-DHT组血清睾酮间无统计学差异(P>0.05),但显著低于INT组(P<0.05);血清DHTORX组低于INT组,HD-DHT组高于LD-DHT组INT组(P<0.05),LD-DHT组和INT组之间无统计学差异(P>0.05),LD-DHT组、HD-DHT组血总胆固醇(TC)低于ORX组(P<0.05),低密度脂蛋白各组之间无统计学差异。HD-DHT组血清甘油三酯(TG)高于INT组(P<0.05),LD-DHT组、ORX组血清TG含量与INT组无统计学差异(P>0.05)。ORX组肝脏重度脂肪变,以大泡性脂滴为主;INT组中度脂肪变,胞浆中有部分脂肪空泡;LD-DHT组仅见轻微脂肪变;HD-DHT组的肝脏组织病理接近正常。结论DHT替代治疗影响血脂代谢,DHT可导致TC降低,同时伴有TG升高;影响血脂代谢的同时明显减少肝细胞脂肪沉积,这些变化均有剂量依赖性。     

The influence of social subordinate housing on the withdrawal effects from progesterone and estradiol in male rats

In this study, we investigated the presence of nerve growth factor (NGF) and its receptors tyrosine kinase A (TrkA) and p75 in the uterus of the wild ground squirrels during the estrous period, early pregnancy and non-breeding period. In the estrous period and early pregnancy, NGF and TrkA were immunolocalized in stromal cells, luminal epithelial cells, glandular cells and smooth muscle cells whereas in the non-breeding period, both of them were detected only in luminal epithelial cells and glandular cells, but not in stromal cells or smooth muscle cells. Stronger immunostaining of NGF and TrkA was observed in luminal epithelial cells and glandular cells in the estrous period and early pregnancy as compared to the non-breeding period. p75 was immunolocalized only in luminal epithelial and glandular cells during the estrous period, early pregnancy and non-breeding period. The intensity of the immunohistochemical signals for p75 did not vary significantly in the estrous period, early pregnancy and non-breeding period. The mean mRNA levels of NGF and TrkA and p75 were significantly higher in the estrous period and early pregnancy as compared to the non-breeding period. Besides, plasma estradiol-17β and progesterone concentrations were higher in the estrous period and early pregnancy than in the non-breeding period, suggesting that the expression patterns of NGF and TrkA are correlated with changes in plasma estradiol-17β and progesterone concentrations. These results indicate that NGF and its receptor TrkA may be involved in the regulation of seasonal changes in the uterine functions of wild female ground squirrels.     

Inhibition by tamoxifen of the effects of estradiol benzoate on lipid metabolism in female quail

The effect of estradiol (EB), tamoxifen (T), and estradiol + tamoxifen on the hepatic function and lipid metabolism in immature female quails was investigated. EB (0.02 mg/day/6 days) induced increases of relative liver weight, of serum cholesterol, bile acid and fatty acid levels, and of liver fatty acid level. Bile acid and fatty acid spectra were modified by this treatment. T alone (1 mg/day/6 days) had a meager effect on these parameters. If associated with EB it thoroughly inhibited the effects of that hormone.     

Effects of androgen replacement on metabolism and physical performances in male hypogonadism

Hypogonadism in men is associated with decreased physical performance. This phenomenon depends on significantly measurable adverse traits in body composition, namely increased body fat content and reduced muscle mass. Physical abilities in hypogonadal men are further hampered by lower oxygen supply due to decreased hemoglobin concentrations and by poor glucose utilization. In addition, dysthymia and lack of necessary aggressiveness contribute to further deterioration of physical features. T substitution can improve lipid and insulin metabolism, resuiting in changes of body composition, such as decreasing fat depots. Growth of muscle fibers can also be observed. Stabilization of the musculo-skeletal system by increased bone density will further contribute to increased physical fitness, reflected by increased strength and endurance. Treatment outcome is strongly influenced by age and training. The issues reviewed strongly support T treatment of hypogonadal men accompanied by regular monitoring.     

Differential effects of neonatal and adult androgen exposure on the growth hormone secretory pattern in male rats

The interactive effects of androgen exposure during neonatal and adult life on the pattern of GH secretion in adult male rats was investigated. Neonatal rats were orchidectomized or sham-operated on days 1-2 of life and injected immediately postoperatively with testosterone propionate (250 micrograms, sc) or vehicle. At 90-130 days of age the rats were bled every 20 min between 9 and 17 h from an indwelling intraatrial catheter. Some neonatally gonadectomized, testosterone- or vehicle-treated rats were also given depot testosterone (15 mg/kg, im) 5-10 days before blood sampling. Plasma GH concentrations were measured by RIA, and the pulsatile secretory patterns were analyzed by the PULSAR computer program. Neonatal orchidectomy resulted in a marked suppression (50-75%) of both the height and duration of GH secretory episodes, while baseline GH levels were higher in neonatally gonadectomized males than in sham-operated controls. Neonatal testosterone replacement therapy restored high amplitude GH pulses. However, the GH pulses of these animals were of significantly shorter duration and occurred more frequently, and baseline GH levels were markedly higher than those in intact male rats. In contrast, neonatally gonadectomized rats treated with testosterone both neonatally and during adulthood exhibited a GH pattern indistinguishable from that in normal males, with high amplitude and long-lasting (103 +/- 8 min) pulses at regular intervals (178 +/- 9 min). A similar masculine GH pattern was seen in neonatally gonadectomized rats given testosterone only during adult life. The present results indicate that high amplitude GH pulses can be induced by either neonatal or adult androgen exposure. However, while neonatal androgens irreversibly cause stimulation of overall GH secretion, only the continuous presence of androgens during adult life can induce a GH secretory pattern, consisting of large surges at regular 3-h intervals separated by a low baseline that is characteristic of normal male rats.