EFFECT OF DEXAMETHASONE ON CELL POPULATION KINETICS IN THE ADRENAL CORTEX OF THE PREPUBERTAL MALE RAT

1974 ◽  
Vol 62 (3) ◽  
pp. 527-536 ◽  
Author(s):  
N. A. WRIGHT ◽  
D. R. APPLETON ◽  
A. R. MORLEY

SUMMARY The effect of a single injection of dexamethasone on adrenocortical cell proliferation was studied in prepubertal male rats using tritiated thymidine. After a short latent period, all zones of the adrenal cortex showed a rapid decrease in both labelling and mitotic indices. After a prolonged period when very low indices were apparent, there was a rapid rise in both proliferative indices with most zones showing a considerable increase above control values. A more detailed study of the initial depression showed that after a latent period of about 5 h the labelling index fell approximately 8 h before the mitotic index. This differential response in the labelling and mitotic indices was consistent with a block in the cell cycle late in the pre-DNA synthetic interval of the cell cycle (G1), with cells being prevented from entering DNA synthesis. This hypothesis was also supported by an experiment involving continuous labelling of control and dexamethasone-treated animals; again after a latent period of 5–6 h, the rate of increase of the continuous labelling index fell as cells became blocked in late G1. By analogy with other tissues, results are interpreted in terms of a direct action of dexamethasone on adrenocortical cells; this steroid-sensitive step in the cell cycle may be important in the control of growth in the adrenal cortex.

1971 ◽  
Vol 49 (4) ◽  
pp. 599-609 ◽  
Author(s):  
N. A. WRIGHT

SUMMARY On the basis of labelling indices measured with tritiated thymidine at intervals throughout its thickness, the adrenal cortex of prepubertal male rats has been divided into four compartments. These are called the glomerular, proliferative, fascicular and reticular compartments, respectively. Labelling indices measured for each compartment showed highest values in the glomerular and proliferative compartments, with values of 6·73% and 7·09% respectively. The fascicular compartment showed a lower index of 3·16% while the reticular compartment gave the lowest value of 1·15%. These differences are further reflected in measurements of the mitotic indices for each compartment. The phases of the cell cycle have been measured by pulse-chase analysis in each compartment, and all phases estimated showed an increase in duration as the inner compartments were approached. The duration of interphase DNA synthesis (ts) was found to be shortest in the glomerular and proliferative compartments, with values of 7·45 and 7·73 h, respectively. The fascicular compartment showed lengthening of ts to 8·56 h, and the reticular compartment gave the highest value of 9·21 h. Similarly, the values obtained for G2 (the post-DNA synthetic interval) and tm (the duration of mitosis), and a calculated value of the cell cycle time all showed a general increase in duration from the outer to the inner compartments. The relation of these results to theories of adrenocortical cytogenesis is discussed, and it is suggested that the differences in cell cycle components can best be explained by the inward migration of cortical cells from the outer compartments.


Development ◽  
1987 ◽  
Vol 100 (4) ◽  
pp. 619-628 ◽  
Author(s):  
D.J. Goldhamer ◽  
R.A. Tassava

Pulse and continuous labelling with [3H]thymidine combined with mitotic index determinations provided data on the kinetics of cell cycling in innervated and denervated early and mid-bud forelimb blastemas of the adult newt, Notophthalmus viridescens. Most or all blastema cells cycle during regeneration and are thus part of the proliferative fraction. At any given moment, however, only 26% of the blastema cells are actively progressing through the cell cycle, with the remainder being in a state of transient quiescence (TQ). The small size of the actively cycling (AC) population may in part explain the relatively slow rate of regeneration exhibited by the adult newt. The pulse-labelling index and mitotic index of denervated blastemas paralleled control values for 48h following nerve withdrawal, but both parameters were significantly reduced by 72h. By 5 days postdenervation, cell cycle activity was essentially zero. The combined pulse and continuous labelling data suggest that nerves may be primarily involved in the entry of TQ cells into the AC population, with subsequent progression through the cell cycle being less dependent on innervation. Relative to controls, no early postdenervation increases in TCA-precipitable [3H]thymidine incorporation, pulse-labelling index or mitotic index were observed.


1968 ◽  
Vol 14 (7) ◽  
pp. 791-797
Author(s):  
S. B. Hrushovetz ◽  
J. C. Wilt ◽  
E. S. C. Lee

It was found that less than 1% of amnion cells, either as membrane biopsies, as trypsinized cell suspensions, or grown as monolayers on glass incorporated tritiated thymidine during a 1-hour incubation period; this was in contrast to HeLa cells in which over 30% of the cell population incorporated tritiated thymidine. Continuous labelling with tritiated thymidine for a 24-hour period with or without colchicine failed to increase the percentage of labelled amnion cells, while a minimum of 80% of the HeLa cells became labelled. Less than 0.1% of the amnion cells were in mitosis, compared to 4% for HeLa cells. Incubation with colchicine for 24 hours failed to increase the percentage of mitotic figures of the amnion cells. It is concluded that most of the primary amnion cells are in the non-proliferative phase of the cell cycle.


2020 ◽  
Vol 26 (3) ◽  
pp. 509-523 ◽  
Author(s):  
Amany Mohamed Shalaby ◽  
Adel Mohamed Aboregela ◽  
Mohamed Ali Alabiad ◽  
Dina Fouad El Shaer

AbstractTramadol is a centrally acting analgesic drug, used for the management of moderate to severe pain in a variety of diseases. The long-term use of tramadol can induce endocrinopathy. This study aimed to evaluate the effect of tramadol dependence on the adrenal cortex and the effect of its withdrawal. Thirty adult male rats were divided into three experimental groups: the control group, the tramadol-dependent group that received increasing therapeutic doses of tramadol orally for 1 month, and the recovery group that received tramadol in a dose and duration similar to the previous group followed by a withdrawal period for another month. Specimens from the adrenal cortex were processed for histological, immunohistochemical, enzyme assay, and quantitative real-time PCR (RT-qPCR) studies. Tramadol induced a significant increase in malondialdehyde level and a significant decrease in the levels of glutathione peroxidase and superoxide dismutase. A significant decrease in the levels of adrenocorticotrophic hormones, aldosterone, cortisol, corticosterone, and dehydroepiandrosterone sulfate was also detected. Severe histopathological changes in the adrenal cortex were demonstrated in the form of disturbed architecture, swollen cells, and shrunken cells with pyknotic nuclei. Inflammatory cellular infiltration and variable-sized homogenized areas were also detected. A significant increase in P53 and Bax immunoreaction was detected and confirmed by RT-qPCR. The ultrastructural examination showed irregular, shrunken adrenocorticocytes with dense nuclei. Dilated smooth endoplasmic reticulum, mitochondria with disrupted cristae, and numerous coalesced lipid droplets were also demonstrated. All these changes started to return to normal after the withdrawal of tramadol. Thus, it was confirmed that the long-term use of tramadol can induce severe adrenal changes with subsequent insufficiency.


1973 ◽  
Vol 59 (3) ◽  
pp. 451-459 ◽  
Author(s):  
N. A. WRIGHT ◽  
D. VONCINA ◽  
A. R. MORLEY

SUMMARY Recently, cell loss by necrosis has been demonstrated in the zona reticularis of the adrenal cortex; such loss is a prerequisite of the centripetal migration theory of adrenocortical cell renewal. Consequently a method has been evolved for the estimation of the rate of cell loss from the z. glomerulosa in prepubertal male rats aged 14 days. The method depends upon measurement of the doubling time for the z. glomerulosa by weighing and serially sectioning adrenal glands at ages from 3 to 120 days, combined with point-counting. The doubling time for the z. glomerulosa at 14 days of age was 120 h. A continuous labelling technique was used to estimate the growth fraction and the cell cycle time. In the z. glomerulosa these were 0·80 and 87 h respectively. These values gave an estimate of the cell production or birth rate of 0·00676 cells/cell/h, or 0·676 cells/100 cells/h, and consequently the potential doubling time (assuming no cell loss) was 102 h. Since the actual doubling time exceeds the potential doubling time, cells must be lost from the z. glomerulosa. This cell loss was found to be taking place at a rate of 0·0010 cells/cell/h, or 0·10 cells/100 cells/h, and the cell loss factor (ϕ) was 0·15. Since necrosis has only been demonstrated in the z. reticularis, and evidently does not occur in the z. glomerulosa, this cell loss rate can be considered to represent the rate at which cells migrate from the z. glomerulosa. It is proposed, therefore, that in the prepubertal animal at least, centripetal cell migration does occur.


Author(s):  
Gamal El-Sokkary

AbstractThe protective effect of melatonin against phenobarbital-induced oxidative stress in the rat liver was measured based on lipid peroxidation levels (malondialedyde and 4-hydroxyalkenals). Cellular proliferation, DNA synthesis and cell cycle duration were quantitated by the incorporation of 3H-thymidine, detected by autoradiography, into newly synthesized DNA. Two experiments were carried out in this study, each on four equal-sized groups of male rats (control, melatonin [10 mg/kg], phenobabital [20 mg/kg] and phenobarbital plus melatonin). Experiment I was designed to study the proliferative activity and rate of DNA synthesis, and measure the levels of lipid peroxidation, while experiment II was for cell cycle time determination. Relative to the controls, the phenobarbital-treated rats showed a significant increase (P < 0.01) in the lipid peroxidation levels (30.7%), labelling index (69.4%) and rate of DNA synthesis (37.8%), and a decrease in the cell cycle time. Administering melatonin to the phenobarbital-treated rats significantly reduced (P < 0.01) the lipid peroxidation levels (23.5%), labelling index (38.2%) and rate of DNA synthesis (29.0%), and increased the cell cycle time. These results seem to indicate that the stimulatory effect of phenobarbital on the oxidized lipids, proliferative activity, kinetics of DNA synthesis and cell cycle time alteration in the liver may be one of the mechanisms by which the non-genotoxic mitogen induces its carcinogenic action. Furthermore, melatonin displayed powerful protection against the toxic effect of phenobarbital.


Development ◽  
1977 ◽  
Vol 37 (1) ◽  
pp. 33-48
Author(s):  
A. R. Smith ◽  
A. M. Crawley

Pulse and continuous labelling with tritiated thymidine are used for a quantitative study of cell division rates in regeneration blastemas. Proliferation is initially uniform; later a proximodistal gradient develops in the mesenchyme, with the highest labelling index at the tip, where practically all cells are shown to be dividing. In the ectoderm there appear to be two growth bands, one close to the stump and the other close to the tip. The results are consistent with the progress zone theory, and agree well with the numerical estimates of growth rates used in our previously reported simulation.


1958 ◽  
Vol 27 (4) ◽  
pp. 415-422 ◽  
Author(s):  
U. K. Rinne ◽  
E. K. Näätänen
Keyword(s):  

2021 ◽  
pp. 074823372110155
Author(s):  
Weizhe Pan ◽  
Shengnan Yu ◽  
Jin Jia ◽  
Junyang Hu ◽  
Liang Jie ◽  
...  

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 424
Author(s):  
Radoslaw Piotr Radzki ◽  
Marek Bienko ◽  
Dariusz Wolski ◽  
Monika Ostapiuk ◽  
Pawel Polak ◽  
...  

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength.


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