PITUITARY AND ADRENAL RESPONSIVENESS IN RATS AFTER PROLONGED TREATMENT WITH ACTH

1963 ◽  
Vol 41 (1) ◽  
pp. 1771-1777
Author(s):  
E. Stark ◽  
J. Fachet ◽  
Katherine Mihály

Prolonged exposure to ACTH considerably increased adrenal responsiveness in the rat both in vivo and in vitro. The last of 5 and 14 daily injections each produced a significantly higher blood corticosterone level than did a single injection. In the presence of ACTH added in vitro, adrenal corticosterone production in animals subjected to prolonged treatment with ACTH significantly exceeded the production per unit of weight and unit of time measured in saline-treated animals. Reduced adrenal responsiveness in the stage of resistance, elicited by formalin as a non-specific stress, cannot be invoked as an explanation for the absence of an increase in corticosterone secretion. The conclusion is that after prolonged exposure to non-specific stress there is no longer any ACTH hypersecretion.Twenty-four hours after the last injection of prolonged ACTH treatment there was inhibition of endogenous ACTH release by the pituitary gland, formalin produced no rise in the corticosterone level of the peripheral blood, and operative trauma caused substantially less ascorbic acid depletion than it did in saline-treated controls, although the plasma corticosterone level was normal or below normal.

1963 ◽  
Vol 41 (8) ◽  
pp. 1771-1777 ◽  
Author(s):  
E. Stark ◽  
J. Fachet ◽  
Katherine Mihály

Prolonged exposure to ACTH considerably increased adrenal responsiveness in the rat both in vivo and in vitro. The last of 5 and 14 daily injections each produced a significantly higher blood corticosterone level than did a single injection. In the presence of ACTH added in vitro, adrenal corticosterone production in animals subjected to prolonged treatment with ACTH significantly exceeded the production per unit of weight and unit of time measured in saline-treated animals. Reduced adrenal responsiveness in the stage of resistance, elicited by formalin as a non-specific stress, cannot be invoked as an explanation for the absence of an increase in corticosterone secretion. The conclusion is that after prolonged exposure to non-specific stress there is no longer any ACTH hypersecretion.Twenty-four hours after the last injection of prolonged ACTH treatment there was inhibition of endogenous ACTH release by the pituitary gland, formalin produced no rise in the corticosterone level of the peripheral blood, and operative trauma caused substantially less ascorbic acid depletion than it did in saline-treated controls, although the plasma corticosterone level was normal or below normal.


1988 ◽  
Vol 66 (8) ◽  
pp. 1139-1143 ◽  
Author(s):  
Gary B. Glavin ◽  
Lorne J. Brandes

N,N-Diethyl-2-[4-(phenylmethyl)-phenoxy]-ethanamine hydrochloride (DPPE) is a para-diphenylmethane derivative that binds selectively and with high affinity to the microsomal antiestrogen binding site (AEBS). Recent studies with DPPE indicate that AEBS is closely related to a lower affinity non-H1, non-H2 histamine site that may be associated with calcium channels; the DPPE–AEBS site is different from that which verapamil binds, however. DPPE, but not verapamil, demonstrates antiproliferative effects in vitro and is antiestrogenic in vivo. We now show that DPPE profoundly inhibits restraint and cold stress and ethanol-induced gastric ulcer formation, accelerates ulcer healing, attenuates the stress-induced rise in plasma corticosterone level, and significantly reduces basal and H2 agonist (dimaprit)-stimulated and, to a lesser extent, bethanechol-stimulated gastric acid output in conscious rats. A nonulcerogenic but prostaglandin-depleting dose of indomethacin completely blocks the inhibitory effects of DPPE on stress ulcer formation. Conversely, verapamil only slightly attenuates dimaprit-stimulated gastric acid secretion and exacerbates ethanol-induced gastric ulcers; its anti-stress ulcer effects are only partially attenuated by indomethacin. These findings support the likelihood that the site of action of DPPE is different from that of verapamil, and that an effect on prostaglandins may, at least in part, contribute to its antiulcer and apparent cytoprotective effects.


1963 ◽  
Vol 205 (6) ◽  
pp. 1083-1088 ◽  
Author(s):  
J. J. Van Goch ◽  
D. De Wied ◽  
E. Schönbaum

Several indices of adrenocorticotropic (ACTH) activity were compared in order to establish the index most suitable for assay purposes, particularly of ACTH in blood. In hypophysectomized rats, the effects of ACTH on adrenal ascorbic acid, cholesterol, and steroid formation in vitro were studied. In intact rats, the effects of formalin on these variables as well as on the adrenal and plasma corticosterone levels and hypophyseal and blood ACTH activity were measured. Adrenal corticosterone as well as steroid formation in vitro increased very rapidly after stimulation by ACTH. In hypophysectomized rats, after intravenous ACTH, significant increases were observed after 5 min. In normal rats, 3 min after the injection of formalin, significant increases of steroid formation in vitro and ACTH activity were observed. The in vitro technique is suitable for the study of changes in ACTH activity. ACTH increases the fraction of corticosterone found in the total amount of corticoid secreted by rat adrenals in vitro.


2005 ◽  
Vol 28 (9) ◽  
pp. 1722-1725 ◽  
Author(s):  
Sew-Fen Leu ◽  
Chi-Hsien Chien ◽  
Chi-Yu Tseng ◽  
Yu-Ming Kuo ◽  
Bu-Miin Huang

1983 ◽  
Vol 61 (7) ◽  
pp. 538-546 ◽  
Author(s):  
François Legros ◽  
Jean-Guy Lehoux

Groups of Long Evans rats were treated with 15 IU ACTH/day for 1–9 days and sacrificed at different intervals during and after treatment. Aldosterone and corticosterone plasma levels were increased above control values for the entire duration of treatment and were decreased to control values as early as 3 days posttreatment. The uptake of [125I]angiotensin II ([125I]AII) by adrenocortical glomerulosa cell suspensions was diminished by 71% at day 9 of treatment and this [125I]AII-uptake capacity slowly returned to control values after cessation of treatment (66.0% of control at day +19). The association constants at equilibrium (Ka) for AII receptors were similar in both treated (0.19 × 109 M−1 at day 9) and control (0.12 × 109 M−1) rats, whereas the number of AII-binding sites was lowered in the glomerulosa cells of treated (Nmax = 6 fmol/50 000 cells) compared with control (29 fmol) animals. In vitro cell suspensions from treated rats had, compared with controls, a lowered basal aldosterone and an increased corticosterone output. Addition of ACTH (10−8 M) to these cell suspensions showed no effect on the aldosterone or corticosterone output, whereas a significant stimulation was observed for cells obtained from control animals. Studies on rats treated 9 days and sacrificed 19 days after cessation of treatment demonstrated that the basal aldosterone and corticosterone output from zona glomerulosa cell suspensions was comparable with that of control rats; the steroid output of these cells could be further stimulated in vitro by addition of ACTH. It is concluded that the chronic ACTH treatment produced (i) a loss of AII receptor of adrenal zona glomerulosa cells, a phenomenon that was reversible 3–4 weeks posttreatment; (ii) a decreased capacity of glomerulosa cells to further respond to ACTH stimuli in vitro, suggesting either a loss of ACTH receptor by these cells or a decrease in activity of enzymes responsible for steroidogenesis, or a lack of endogenous precursor; (iii) a diminution of the thickness of the zona glomerulosa accompanied by an enlargement of the zonae fasciculate–reticularis, resulting in high circulating plasma corticosterone. This high plasma corticosterone level might well be the source of the precursor used in vivo by the zona glomerulosa to maintain the observed high plasma aldosterone level, despite the lowered overall steroidogenic capacities of these cells demonstrated by our in vitro studies.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Nahed El-Najjar ◽  
Rashmi P. Kulkarni ◽  
Nancy Nader ◽  
Rawad Hodeify ◽  
Khaled Machaca

Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca2+signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model. We find that prolonged exposure of A7r5 cells to hyperglycemia (weeks) is associated with changes to Ca2+signaling, including most prominently an inhibition of the passive ER Ca2+leak and the sarcoplasmic reticulum Ca2+-ATPase (SERCA). To translate these findings to the in vivo condition, we used primary VSM cells from normal and diabetic subjects and find that only the inhibition of the ER Ca2+leaks replicates in cells from diabetic donors. These results show that prolonged hyperglycemia in isolation alters the Ca2+signaling machinery in VSM cells. However, these alterations are not readily translatable to the whole organism situation where alterations to the Ca2+signaling machinery are different.


Author(s):  
Senthil Murugan Murugaiyan ◽  
Rajesh Bhargavan

AbstractObjectivesAluminium is present in food preparations, antacids and many medications. It causes neurodegeneration thereby resulting in a spectrum of neurological disorders such as dementia, Alzheimer’s disease and anxiety. Bacopa monnieri (BM) is widely used in ayurvedic medicine to improve memory functions. Its anxiolytic property was investigated in this study by using elevated plus maze (EPM) and plasma corticosterone level.MethodsThirty rats were assigned into five groups. Control group received distilled water, and 0.5% tween 80, AlCl3 group received Aluminium Chloride (AlCl3), Protective groups (BM100 + AlCl3 group and BM200 + AlCl3 group) received AlCl3 and BM at two different doses, and the BM200 group received BM. The EPM experiment was performed at the end of the 4th week of oral administration of BM and AlCl3 followed by the measurement of plasma corticosterone.ResultsOral administration of AlCl3 to rats increases the levels of anxiety as seen in a decrease in the percentage of entries into the open arms of EPM, an increase in grooming frequency and defecation index. However, the rats in the protective groups shown an increase in the percentage of open arm entries and rearing frequency, and decreased grooming frequency and defecation index. AlCl3 alone treated group showed a significant increase in the plasma corticosterone levels compared to the control group. Whereas the protective groups have shown a significant decrease in the plasma corticosterone levels than the AlCl3 alone treated group.ConclusionsHence the BM has potential role in reverting the anxiogenic effect of AlCl3 in the amygdala as it is evident from the plasma corticosterone levels and the EPM parameters of different groups under study.


2020 ◽  
Vol 3 (1) ◽  
pp. 01-21
Author(s):  
Faisal Ali

Noni (Morinda citrifolia L.) is being evaluated in laboratory research for its benefits as an antioxidant and immunity booster, as well as for its properties to prevent tumors and cure diabetes. The vast spread of Noni in tropical region of the globe, from America reaching to Africa and Southeast Asia, contributed in enhancing its usage and potency due to the diversity in harvest zone. Noni parts comprise fruits, seeds, leaves, and flowers are being used for individual nutritional and therapeutical values. Nevertheless, the fruit is widely characterized to contain the most valuable bioactive substances. On the other hand, diabetic retinopathy (DR) is a microvascular disorder impacting the small blood vessels in the retina, which includes microaneurysms, retinal hemorrhages, and hard exudates results from prolonged exposure to high blood glucose levels. The anti-diabetes effect of Noni extract and juice has been examined but the beneficial role of Noni and its potential mechanisms against the development of diabetic retinopathy phenotype is still ambiguous. This review, therefore, will discusses in details the pharmacological actions of M. citrifolia fruit, along with their isolated phytochemical compounds on diabetic retinopathy markers, through describing the conducted in vitro and in vivo studies as well as clinical data.


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