Disuse of a limb has been repeatedly demonstrated to cause pronounced atrophy of skeletal muscle. In animals and humans, disuse of a leg due to immobilization can cause pronounced catabolism of many skeletal muscle proteins. Strength, V02 max, oxidative enzyme activities, protein synthesis, and muscle weight are all diminished due to chronic limb immobilization.Testosterone is classified as an anabolic steroid which has the effect of increasing protein synthesis in many tissues. Recently, testosterone has been shown to have a definite anti-catabolic effect on skeletal muacle by competing with glucocorticoids for binding proteins within the muscle cell. This reduces the effect of the circulating catabolic hormones. By slowing protein breakdown and increasing protein synthesis in the skeletal muscle of an immobilized limb, testosterone could effectively delay the rapid atrophy so often seen.To examine the effects of testosterone on skeletal muscle atrophy during limb immobilization, forty albino, male rats were randomly divided into four groups of ten. Group I served as the non-immobilized control and received daily placebo injections of sesame oil. The rats in group II were castrated and their hindlimbs were immobilized using a plaster cast. The animals in this group also received daily injections of sesame oil. The group III rats were also castrated and casted, but they received a daily injection of 5 mg testosterone propionate. The animals in group IV were not castrated but were casted.These rats also received a daily injection of testosterone. The duration of treatment was two weeks for each rat. Body weights were measured before and after treatment. The gastrocnemius, quadriceps, soleus, and cardiac muscles were weighed after treatment. Oxygen consumption capacity (Q02), citrate synthase activity, total protein, and percentage of water were also measured in the gastrocnemius, quadriceps, and cardiac tissues.The results of this study demonstrate that hindlimb immobilization not only causes severe atrophy in those muscles immobilized, but has an overal catabolic effect on the animal. Along with the effects on muscle and body size, the immobilization also significantly reduced the aerobic capacity of affected muscle groups and cardiac tissue. The study also gave evidence that testosterone, or the lack of it, can affect the rate of muscle atrophy. The greatest reduction in body weight, muscle size, heart size, and QO2 were seen in the castrated group which only received a placebo injection of sesame oil. The anti-catabolic effect of testosterone was evedent in groups III and IV.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

(Uncorrected OCR) Abstract of thesis entitled Telomerase activation and telomeric repeats alteration in sex hormone-induced prostatic carcinogenesis in the Noble rat submitted by Chan Ching for the Degree of Master of Philosophy at the University of Hong Kong In November, 1998 Despite its distinction as the most frequently diagnosed cancer and the�second leading cause of cancer deaths in men, little is known about the causes and mechanisms of prostatic carcinogenesis. The animal model, based on the existing sex hormone-induced prostate carcinogenesis in the Noble rat, by substantially increasing the dosage of testosterone while keeping the level of estrogen unchanged has been reported. With this modified protocol, we have successfully induced high incidence of prostate carcinoma in Noble rats. The earliest time of development of dysplasia was two months, carcinoma in situ at 4 months and fully developed carcinoma at six months. The tumor incidence was 92% after 12 months hormonal implantation. This animal model is very useful in the investigation of prostate cancer as its multi -step nature mimics the human situation and its high incidence in relative short time. Telomerase activation is a characteristic of immortalized tumor cells and is thought to contribute to the mechanism by which these cells abort the normal process of senescence. Telomerase activity has been detected in various human cancers and there are reports showing that telomeric repeat fragment (TRF) length may be correlated to the staging of tumors. These findings suggested that telomerase activation and TRF length alteration might be useful in prognosis of different cancers. Study of prostate cancer on animal model can compensate for the difficulties in human cancer research, as stage-by-stage investigations are available. In this study, we proposed that telomerase would be activated in sex hormone-induced prostatic carcinogenesis and TRF length alterations might be correlated to the different stages of prostatic carcinogenesis. We have examined the telomerase activation as well as telomeric repeat fragment content alteration in the hormonal induced prostatic carcinogenesis in Noble rat. Telomerase activation is common in prostate carcinoma and also can be detected in 12% of non-malignant tissues. For the non-prostatic tissues tested, all the testis tissues (n=5) were strongly positive for telomerase activity and only one liver tissue (n=5) showed weak. telomerase activity. The high frequency of telomerase activation in prostatic carcinoma specimens suggested that it might be a useful malignancy marker for prognosis evaluation in prostatic carcinogenesis. There were alterations of TRF content in dorsal lateral prostate. The ventral prostate tissues have the similar results as the dorsal lateral prostate. It seems that the TRF content in normal tissues is less than that of hyperplasia, dysplasia and carcinoma tissues. However, no obvious relationships between the TRF content and clinicopathological properties of prostatic carcinogenesis were observed. Also, there was no significant relation between the telomerase activation and TRF content in this study. Hence, the TRF content appear to have no significant correlation with prostatic carcinogenesis. / abstract / toc / Anatomy / Master / Master of Philosophy

published_or_final_version / Physiology / Master / Master of Philosophy

published_or_final_version / Physiology / Master / Master of Philosophy

No description available.

The morphological and physiological effects of pineal gland activity on the prolactin-secreting cells of the anterior pituitary were examined in blind-anosmic male and female rats. Prolactin synthesis was measured by the ability of anterior pituitaries to incorporate ³H-leucine into prolactin in vitro. Pituitary storage of prolactin was assessed by measuring radioimmunoassayable prolactin levels in the pituitaries in vivo and the total amount of immunoassayable prolactin in vitro. The effects of the activated pineal on prolactin release were estimated by monitoring radioimmunoassayable serum prolactin levels. Finally, the morphology of the prolactin cells was analyzed by both light microscopic immunocytochemistry and transmission electron microscopy. Eight weeks after blinding and olfactory bulbectomy in prepubertal male and female rats, prolactin synthesis, storage and release were all significantly decreased compared to unoperated control values. Pinealectomy in blind-anosmic rats completely prevented these effects. Similar results were obtained four weeks after treatment, but not after only one week. Furthermore, the reductions in prolactin synthesis, storage and release were not a consequence of the pineal-induced gonadal atrophy in these animals, since these effects persisted in ovariectomized-blind-anosimic rats. The pineal also elicited these effects in female rats rendered blind-anosmic after puberty, though to a lesser degree than when immature animals were used. Concomitant with these alterations in prolactin synthesis, storage and release were regressive changes in the morphology of individual prolactin cells and in the number of these cells in the pituitary. Anterior pituitaries from blind-anosmic rats were approximately half the weight of glands from intact animals and contained a third less DNA. This loss of cell number was largely accounted for by a reduction in the number of prolactin cells, as shown by immunocytochemistry. Additionally, each prolactin cell was smaller in size in blind-anosmic female rats and showed scant endoplasmic reticulum, a small Golgi complex, few secretory granules and rare exocytosis patterns. From these data I conclude that the pineal gland exerts a strong inhibition on the prolactin cells of blind-anosmic rats.

No description available.

No description available.

Sixty-nine female Wistar rats were studied to determine if the oxidative capacity and glycogen concentration of skeletal muscle was affected by either an increase or decrease in training duration following a 9 wk program of treadmill running. Initially, 30 rats were randomly assigned to one of three sedentary control groups. Subgroups (N=10) of sedentary animals were kept inactive and were sacrificed at week 0 (Cl), week 9 (C2) and week 11 (C3) of the study. Thirty-nine rats were initially trained 5 days/wk for 9 wks using a standard exercise protocol. At the end of 9 wks of treadmill running, endurance trained animals were separated into four groups: 1) Eleven rats (ET) were killed. 2) Ten rats (CT) continued to train for 2 additional weeks following the same protocol and were killed at the end of 11 wks of training. 3) Ten rats (DT) decreased the duration of daily running by 66% and after 14 days were killed. 4) Eight rats (IT) increased the duration of daily running by 500% in an attempt to simulate overtraining in humans, and after 6 days were killed. The respiratory capacity (Qo2) and citrate synthase activity (CSA) of the soleus (SOL) and plantaris (PLANT) muscles were significantly increased (p< 0.05) over all control groups by nine weeks of treadmill running (ET). The Qo2 and CSA of CT rats were significantly higher than all control groups, and the PLANT CSA was significantly higher (p< 0.05) than ET rats. The SOL and PLANT Qo2 and CSA remained significantly higher (p< 0.05) than all control groups with fourteen days of decreased training. Six days of increased training significantly increased (p< 0.05) SOL and PLANT Qo2 and CSA over all control groups. In addition IT rats had SOL and PLANT CSA that were significantly higher (p< 0.05) than ET rats. The SOL and WV glycogen concentrations were unaffected by all training protocols. Only the CT and IT PLANT and liver had significantly more (p< 0.05) glycogen than all sedentary control groups. The results of this study indicate that the rat is a very adaptable animal, and to thoroughly study it as a possible model for the study of overtraining in humans would require an examination of various exercise protocols. In addition, the exercise-induced increase in the oxidative capacity of trained skeletal muscle is not readily reversible during decreased training.