The influence of norethindrone and mestranol on pituitary–adrenal function

1968 ◽  
Vol 46 (4) ◽  
pp. 694-697 ◽  
Author(s):  
David R. Usher

Female Wistar rats were force-fed either Ortho-Novum (66 μg norethindrone and 1 μg mestranol), norethindrone (66 μg), mestranol (1 μg), or water daily for 1 month. After decapitation, organs were weighed, plasma was analyzed for corticosterone concentration, and the adenohypophyseal ACTH content was assayed. Animals treated with Ortho-Novum and mestranol showed a significant ovarian, adrenal, and pituitary weight loss; this was more marked after mestranol. Mestranol also produced a significant uterine atrophy. Norethindrone lowered adrenal weight but had little effect on the other organ weights. Adenohypophyseal ACTH content was significantly decreased after norethindrone but not after mestranol. On the basis that the effects of norethindrone may have been due to estrogenic contaminants, rigorously purified norethindrone was used in a further study. No effects were seen on organ weights although some decrease in pituitary ACTH was still observed. Thymus weight and plasma corticosterone levels were unaltered by any of the treatments. It would appear that increasing estrogenicity (pure norethindrone < crude norethindrone < Ortho-Novum < mestranol) resulted in a decrease in the weight of both the pituitary and the adrenals, and an increased ACTH storage in the adenohypophysis.

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9438
Author(s):  
Eduardo Cienfuegos-Pecina ◽  
Tannya R. Ibarra-Rivera ◽  
Alma L. Saucedo ◽  
Luis A. Ramírez-Martínez ◽  
Deanna Esquivel-Figueroa ◽  
...  

Background Ischemia–reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. Methods (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. Results (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. Conclusion None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.


2012 ◽  
Vol 46 (2) ◽  
pp. 101-107 ◽  
Author(s):  
M Moraal ◽  
P P A M Leenaars ◽  
H Arnts ◽  
K Smeets ◽  
B S Savenije ◽  
...  

Ad libitum (AL) supply of standard chow is the feeding method most often used for rodents in animal experiments. However, AL feeding is known to result in a shorter lifespan and decreased health as compared with restricted feeding. Restricted feeding and thus limiting calorie intake prevents many health problems, increases lifespan and can also increase group uniformity. All this leads to a reduced number of animals needed. So-called standard chows are known to be prone to variation in composition. Synthetic foods have a more standard composition, contributing to group uniformity which, like diet reduction, may decrease the number of animals necessary to obtain statistical significance. In this study, we compared the effects of AL versus restricted feeding (25% reduction in food intake) on standard chow versus synthetic food of three different suppliers on body weight (BW), growth, several blood parameters and organ weights in growing female Wistar rats over a period of 61 days. Diet restriction led to a decreased growth and significantly reduced variation in BW and growth as compared with AL feeding. AL feeding on synthetic diets caused a significantly higher BW gain than on chow diets. Due to experimental design, this same effect occurred on food restriction. Blood parameters and organ weights were affected neither by diet type nor by amount. Incidentally, variations were significantly reduced on food restriction versus AL, and on synthetic diets versus chow diets. This study demonstrates that food restriction versus AL feeding leads to a significantly reduced variation in BW and growth, thereby indicating the potential for reduction when applying this feeding schedule.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3070
Author(s):  
Halina Zofia Staniek ◽  
Ewelina Król ◽  
Rafał Wojciech Wójciak

The aim of the study was to evaluate the main and interactive effects of chromium(III) propionate complex (Cr3) supplementation and different iron supply on the carbohydrate metabolism, lipid profile and other selected biochemical parameters of rats. The experiment was carried out in a two-factor design, in which rats were fed a diet with different proportions of Fe(III) and Cr(III) for six weeks. Fifty-four healthy female Wistar rats were divided into nine experimental groups with different Fe(III) levels, i.e. adequate—control group (45 mg/kg)—100% recommended daily dietary dose of Fe for rodents, deficient (5 mg/kg) and oversupply (180 mg/kg—400%). At the same time they were supplemented with Cr(III) of doses 1 (adequate), 50 and 500 mg/kg of diet. The activity and concentrations of most biochemical parameters were measured with standard enzymatic, kinetic, and colorimetric methods. HOMA-IR and QUICKI indexes were calculated according to appropriate formulas. It was found that there was an interactive effect of high Cr(III) doses and different Fe(III) levels in the diet on the carbohydrate metabolism and insulin resistance indexes. The presented results suggested that iron deficient diet fed animals led to insulin resistance; however, an effect is attenuated by Cr(III) supplementation at high doses. There were no significant changes in the rats’ lipid profile (except for the high density lipoprotein cholesterol (HDL-C) level) and most of the other biochemical parameters, such as the leptin, aspartate aminotransferase (AST), alanine transaminase (ALT), total protein (TP), creatinine (Crea) and the urea (BUN) concentrations. The study proved that the Cr(III) supplementation, independently and in combination with diversified Fe(III) content in the diet, affected the carbohydrate metabolism and insulin resistance indexes but did not affect lipid profile and most of the other biochemical parameters in healthy rats. The findings proved the role of Fe and Cr(III) and their interactions on disturbances carbohydrates metabolism.


1967 ◽  
Vol 125 (3) ◽  
pp. 501-510 ◽  
Author(s):  
Joseph R. Bianchine ◽  
Norman R. Eade

The cotton pellet technique was used to evaluate the effect of 5-HT and certain related compounds on granuloma formation in the rat. 5-HT (10 mg/kg) significantly decreased granuloma formation, significantly increased adrenal weight, and significantly decreased thymus weight in normal rats, and significantly decreased granuloma formation and thymus weight in sham-operated rats. On the other hand, 5-HT (10 mg/kg) significantly increased granuloma weight in adrenalectomized rats. Methysergide (1 mg/kg) blocked the inhibitory effect of 5-HT on granuloma formation as well as the changes in weight of adrenal and thymus glands. 5-HIAA (11 mg/kg) and 5-HTP (13 mg/kg) failed to alter granuloma formation.


1959 ◽  
Vol 196 (3) ◽  
pp. 520-524 ◽  
Author(s):  
Henry B. Hale ◽  
Roy B. Mefferd ◽  
Gordon Vawter ◽  
G. Elizabeth Foerster ◽  
Dominic Criscuolo

A comparison was made of the morphological effects of cold, heat and simulated altitude on adult male rats given exposures of 24 weeks' duration. By the use of covariance analysis it was possible to determine the extent to which organ weights were dependent upon body weight and to adjust the values in order to remove body weight influences. For liver, heart and kidney, adjusted weights indicated temperature-dependency, while pressure-dependency was established for liver and kidney only. Histologically, temperature-dependency was indicated for liver, kidney, thyroid, adrenal and pituitary. Fur weight was reduced in heat but not altered in cold. Fasting in cold induced changes in adrenal and thymus weight and unusually high body weight loss; in heat, fasting caused a significant thymus weight loss without adrenal weight increase. The thymus-adrenal ratio was elevated during a 24-hour fast in all environments except cold, where it was decreased.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ivana Cristina Nunes Gadelha ◽  
Michelly Fernandes de Macedo ◽  
Sílvia Catarina Salgado Oloris ◽  
Marilia Martins Melo ◽  
Benito Soto-Blanco

The present study aimed to determine if gossypol interferes with ovarian follicles in rats. Twenty-four female Wistar rats were assigned to two equal groups: one control group and the other dosed with gossypol (25 mg/kg/day, subcutaneously) for 15 days. Ovarian follicles were histologically classified according to the stage of development and as normal or atretic. Gossypol treatment reduced the length of estrous with an increase in the duration of the diestrus phase. This compound was responsible for reduced serum levels of T4 and progesterone. Treatment with gossypol was responsible for a significant reduction in the number of normal ovarian follicles and a significant increase in the number of atretic follicles, both in all stages of development. Thus, treatment of rats with gossypol was responsible for reduction in the number of viable follicles and changes in hormone levels that resulted in interference of the estrous cycle.


1956 ◽  
Vol 187 (2) ◽  
pp. 353-356 ◽  
Author(s):  
John J. Christian

The adrenal glands increase and the thymus and secondary reproductive organs decrease in weight when mice are placed in groups. These changes in weight are related to the size of the population or group and presumably are a reaction to sociopsychological pressures. If such a presumption is correct, reserpine should diminish the differences in the organ weights of grouped and of isolated mice. Grouped and isolated male mice were given 40–50 µg of reserpine (Serpasil, Ciba) per day in their drinking water and the results compared with those from similar numbers of grouped and isolated mice without reserpine. The average number of fights per 10-minute interval per day was 51.4% less in the treated than in the untreated mice for the first 3 days after grouping. Grouped mice, treated and untreated, had heavier adrenals and lighter thymus glands and secondary reproductive organs than their isolated controls. Treatment of grouped mice with reserpine was accompanied by a 5% lower adrenal weight, 28% greater thymus weight, and 12% greater seminal vesicle weight than were found in the untreated grouped mice. Reserpine treatment resulted in apparently comparable changes in the weights of these organs in isolated mice, but the differences were neither as great nor were they significant with the exception of the thymus gland. It was concluded that a) male mice responded to grouping with increases in adrenal weight and decreases in the weights of their thymus glands and secondary reproductive organs whether or not they had received reserpine; b) the response to grouping was not as great in the animals which had received reserpine; c) treatment with reserpine alone effects a reduction of adrenal weight and increases in the weights of the thymus and secondary reproductive organs; and d) reserpine reduces aggressiveness as measured by the number of fights between mice in groups.


1984 ◽  
Vol 18 (3) ◽  
pp. 298-314 ◽  
Author(s):  
R. G. Pickering ◽  
C. Elizabeth Pickering

Each of 5 groups of 50 weanling Wistar-derived female rats was fed a different diet ad libitum for 2 years. The diets included 3 commercial maintenance diets (R and M No. 1, R and M No. 491 and RDM 22), a purified or semi-synthetic diet (LJ 80) and the diet (LAD 2) normally used in this laboratory. A weighed amount of LAD 2 diet (less than would be consumed under ad libitum conditions) was fed each day to a 6th group of rats. The survivals of the groups of rats fed either the standard diet (LAD 2) in restricted amount or the maintenance diet (RDM 22) were 62% and 66% respectively and were significantly better than the 40% survival of the group fed LAD 2 ad libitum. The survivals of the groups fed either Rand M No. 491 or LJ 80 were 40-42%, and the group fed Rand M No. 1 had a survival of 52%. At the end of 2 years the 2 groups with the best (>60%) survivals weighed significantly less than the group fed LAD 2 ad libitum. The groups fed either LAD 2 in restricted amount or RDM 22 had the least gross pathological lesions for the majority of the organs. These same groups also had fewer pituitary tumours per group (72% and 66%) than the group fed LAD 2 ad libitum (90%). The group fed RDM 22 also had the largest % (26%) of normal pituitaries of all the groups in the study. There were some significant differences between the haematological and clinical chemistry results of the group fed LAD 2 ad libitum and the other groups but none of the changes was considered adverse, although the groups fed either RDM 22 or Rand M No. 491 had significantly increased mean aminotransferase (AST and ALT) values with large variations which were adjudged undesirable. There was less protein in the urine of the groups fed either RDM 22 or LAD 2 (restricted).


1971 ◽  
Vol 68 (4) ◽  
pp. 737-748
Author(s):  
Torsten Perklev

ABSTRACT A single injection of a long-acting oestrogen, polydiethylstilboestrol phosphate (PSP; 200 μg/100 g body weight), into adult male rats caused an enlargement of the adrenal glands and an approximate doubling of total adrenal 3β-hydroxysteroid dehydrogenase (3β-OHD) activity and plasma corticosterone concentration in animals sacrificed 11 to 14 days following injection. The administration of interstitial cell stimulating hormone (ICSH) of human origin or a long-acting testosterone ester (Andradurin®) into the PSP-treated animals partially or completely counteracted the effects of the PSP treatment on adrenal weight and 3β-OHD activity. Daily injections of corticotrophin (ACTH) into intact male rats for 7 days caused a significant rise in the adrenal 3β-OHD activity. Gonadectomy of male rats resulted in increased adrenal weights and elevated adrenal 3β-OHD activity. The plasma corticosterone concentration was unaffected. PSP treatment significantly augmented the effects of the gonadectomy on the adrenal weight and 3β-OHD activity and caused an elevated plasma corticosteroid concentration. The adrenal enlargement following gonadectomy was completely reversed by testosterone replacement but was not influenced by daily injections of ICSH. The data are interpreted as suggesting that the oestrogen-induced hyper-secretion of ACTH in the male rat may be mediated through an elevated activity of the corticosteroid-binding globulin, caused by a reduced plasma testosterone level and a stimulated thyroid activity.


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