The effect of urethane on pituitary-adrenal function of female rats

1984 ◽  
Vol 106 (3) ◽  
pp. 362-367 ◽  
Author(s):  
William N. Hamstra ◽  
Deborah Doray ◽  
Jon D. Dunn

Abstract. Urethane anaesthesia resulted in rapid and sustained increase in plasma corticosterone levels of adult female rats both in the (a.m.) AM and (p.m.) PM. Initial corticosterone levels of non-injected control rats showed marked AM-PM differences (i.e., 28.3 μg/dl and 52.6 μg/dl, respectively), but by 10 min post-injection, the morning corticosterone levels were increased (76.2 μg/dl) such that AM-PM differences were not observed. By 30 min post-injection, PM plasma corticosterone levels had increased significantly (88 μg/dl) but were not different from AM values for the remainder of the 2 h experiment. Saline injected controls showed the expected response to stress; plasma corticosterone levels were increased (P < 0.01) at 10 min but were back to baseline by 45 min (9.0 μg/dl). Dexamethasone (100 μg/dl). sc) markedly suppressed both AM and PM urethane-stimulated corticosterone levels. However, diurnal differences in dexamethasone suppression were noted; whereas morning plasma coticosterone levels averaged 24.8 μg/dl over the five sampling times corresponding PM values averaged 54.3 μg/dl. Plasma corticosterone levels of non-anaesthetized, hypophysectomized ACTH-primed and injected rats were not different from those similarly treated and anaesthetized with urethane and urethane-induced increases in corticosterone were not abolished by hypothalamic isolation (HI). However, plasma corticosterone levels of HI rats were less than those of shamoperated controls (i.e., 58 μg/dl and 74 μg/dl, respectively). Collectively, these data indicate that urethane evokes a sustained increase in pituitary-adrenal activity, that the increased activity is dexamethasone sensitive and that a site of action for pituitary-adrenal activation is, at least in part, at the level of the hypothalamo-hypophyseal complex.

1977 ◽  
Vol 198 (1132) ◽  
pp. 297-314 ◽  

Lesions of the suprachiasmatic nuclei that caused failure of spontaneous ovulation in female rats consistently produced abnormalities in other functions that are normally influenced by the light-dark cycle. In such animals morning plasma corticosterone concentrations were abnormally high and evening values abnormally low though the response to stress was unaffected. Pineal serotonin N -acetyl transferase activity was abnormally high in animals killed during the day and abnormally low in those killed at night. Although the animals were in persistent be­havioural oestrus, total voluntary wheel-running activity was not con­sistently altered but was distributed evenly between the light and dark periods rather than being confined principally to the dark periods as in normal animals. Similarly the proportion of the daily water and food intake that occurred during the dark period was reduced. The incidence of these associated abnormalities was low in lesioned rats that continued to ovulate spontaneously.


1978 ◽  
Vol 88 (4) ◽  
pp. 744-753 ◽  
Author(s):  
Silvia B. Vasquez ◽  
Julian I. Kitay

ABSTRACT The influence of prolactin treatment (100 μg/100 g body wt. sc daily for 7 days) on plasma corticosterone levels, adrenal steroid production in vitro and in vivo and pituitary-adrenal responses to stress were studied in intact and castrated female rats. Prolactin enhanced plasma corticosterone levels and corticosterone production in vitro and in vivo in intact rats after stress. Differences were abolished with ACTH treatment. In contrast, prolactin administration to ovariectomized rats inhibited plasma corticosterone response to stress. Combined treatment with ACTH reversed these findings. A greater in vitro production of corticosterone by adrenal slices and adrenal homogenates associated with an effective inhibition of adrenal 5α-reductase activity were also observed. Secretion of DHB in adrenal venous blood was decreased as well, without changes in corticosterone or THB secretion rates. However, combined treatment with prolactin and ACTH produced greater increments in secretion rates of corticosterone than those obtained with prolactin alone. The data suggest that prolactin treatment to ovariectomized rats has a dual effect: a) adrenal responsiveness to ACTH is enhanced by its effects on adrenal 5α-reductase activity, and b) pituitary-adrenal response to stress is dampered by prolactin treatment. The effects of prolactin on adrenal 5α-reductase activity and corticosterone production in vitro were paralleled in vivo only after the exogenous administration of ACTH. The presence of the gonads apparently prevented the inhibitory effect of prolactin on ACTH secretion and in turn seemed to act synergistically with prolactin to facilitate pituitary-adrenal response to stress.


1974 ◽  
Vol 62 (1) ◽  
pp. 93-99 ◽  
Author(s):  
P. A. SCHLEIN ◽  
M. X. ZARROW ◽  
V. H. DENENBERG

SUMMARY Lactating female rats are known to exhibit a reduced or 'buffered' plasma corticosterone response to stress. The depressed response is a post-partum phenomenon seen only in the lactating rat with pups, since a lactating rat whose pups have been removed for 8 days gives a normal response to ether stress. Thus it appears that lactation may be necessary for a reduced response to stress, and the reappearance of the normal response coincides with the time when the animal resumes its oestrous cycle. Maternal behaviour by itself could be ruled out as a causative factor since a normal adrenal response was seen in virgin rats which had been sensitized to pups. A depressed corticosteroid response to ether stress was obtained after ovariectomy or treatment with prolactin (2 mg/day for 5 days). However, the effect of ovariectomy on plasma corticosterone levels after ether stress could be reversed by the injection of 5 μg oestradiol benzoate daily for 5 days. The minimum effective dose of dexamethasone phosphate that was necessary to prevent increased plasma corticosterone levels after ether stress in the normal female rat was 400 μg/100 g body weight whereas a lactating rat required only 6·25 μg and a virgin rat treated with prolactin required 25 μg. It is apparent that prolactin is acting, in part at least, to increase the sensitivity of the negative feedback system.


1981 ◽  
Vol 241 (1) ◽  
pp. R21-R24 ◽  
Author(s):  
R. G. Doell ◽  
M. F. Dallman ◽  
R. B. Clayton ◽  
G. D. Gray ◽  
S. Levine

These experiments were undertaken to investigate the mechanism whereby a precipitous drop in plasma corticosterone concentration is brought about following drinking in rats on a restricted water schedule. No alteration in adrenocorticotrophic hormone (ACTH) output was found, nor was catabolism of corticosterone sufficient to account for the drop. It is concluded that corticosterone level is controlled under these conditions by a mechanism independent of ACTH concentration.


1988 ◽  
Vol 119 (3) ◽  
pp. 339-344 ◽  
Author(s):  
Jon D. Dunn ◽  
Jerald J. Killion

Abstract. We previously have shown that melittin evokes a sustained increase in plasma corticosterone levels of the female rat. Significant increases occurred only during the morning and the duration of the response was increased from 48 h to 8 days by a second milittin injection 3 days after initial exposure to melittin. To further evaluate the effect of melittin on adrenocortical function, rats were given melittin at 09.00 h on days 1 and 4 and on day 8 rats were subjected to a variety of different stresses. Saline-injected rats served as controls. Blood for determining non-stress and stress levels of corticosterone concentration (RIA) was collected by decapitation. In all cases morning but not afternoon non-stress plasma corticosterone levels of melittin-injected rats were higher than those of saline-injected controls; afternoon non-stress corticosterone levels did not differ between groups. Melittin- and saline-treated rats showed comparable corticosterone responses to a morning 2-min restraint stress. In contrast, melittin treatment facilitated the pituitary-adrenal response to rotational and surgical stress as well as the stress of removing one rat from a cage of two. Fifteen min after removal of the first rat of a cage of two, plasma corticosterone levels of the melittin-injected rat were significantly higher than those of saline-injected rats. Likewise, plasma corticosterone levels of melittin-treated rats were higher (P < 0.05) than those of saline-injected rats 15 min after rotational (10 rpm) and surgical (jugular cutdown and blood withdrawal) stress. Collectively these data indicate that exposure to melittin (and/or the resulting increase in morning corticosterone levels) may have a significant influence on the pituitary-adrenal responsiveness to stress.


2020 ◽  
Vol 21 (20) ◽  
pp. 7440
Author(s):  
Enrico Ullmann ◽  
George Chrousos ◽  
Seth W. Perry ◽  
Ma-Li Wong ◽  
Julio Licinio ◽  
...  

Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffling and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.


2003 ◽  
Vol 88 (7) ◽  
pp. 3113-3116 ◽  
Author(s):  
Eleni V. Dimaraki ◽  
Craig A. Jaffe

After evaluating a patient who appeared to have a falsely abnormal response to the dexamethasone suppression test while taking troglitazone, we examined the effects of troglitazone on the activity of hepatic CYP3A4 and the screening tests for Cushing’s syndrome. We studied five healthy women and three healthy men, aged 25 ± 2 yr, before and after treatment with troglitazone (600 mg daily) for 28 d. Baseline 0800 h cortisol and corticosterone were similar before and after troglitazone treatment. Before troglitazone treatment, all subjects suppressed 0800 h cortisol below 1.8 μg/dl (mean, 0.66 ± 0.08 μg/dl) during the 1-mg overnight dexamethasone suppression test (DST), whereas during troglitazone treatment none of the subjects suppressed 0800 h cortisol below 1.8 μg/dl (mean, 9.0 ± 1.8 μg/dl). Serum dexamethasone levels decreased by 66 ± 4%, and the erythromycin breath test measurements increased by 27 ± 8%, indicating increased CYP3A4 activity during troglitazone treatment. The hydrocortisone suppression test (HST) was performed by administering 50 mg hydrocortisone at 2300 h. Using the criterion of suppression of 0800 h plasma corticosterone by more than 50%, the specificity of the HST was 100% both before and after troglitazone treatment. In conclusion, troglitazone induced the activity of CYP3A4 leading to falsely abnormal DST. HST is a useful alternative to the DST in patients taking medications that increase the activity of CYP3A4.


2007 ◽  
Vol 292 (4) ◽  
pp. E1173-E1182 ◽  
Author(s):  
Helmer F. Figueiredo ◽  
Yvonne M. Ulrich-Lai ◽  
Dennis C. Choi ◽  
James P. Herman

It is well established that estrogens markedly enhance the glucocorticoid response to acute stress in females. However, the precise mechanism responsible for this regulation is poorly understood. Here, we tested whether estrogens enhance the activation of the paraventricular nucleus (PVN) of the hypothalamus by measuring stress-induced c- fos mRNA expression in the PVN of restraint-stressed ovariectomized (OVX) rats treated with physiologically relevant doses of estradiol (E2), the major female estrogen. As expected, E2 enhanced plasma corticosterone responses to restraint in OVX females. However, E2 markedly attenuated the stress-induced c- fos gene expression in the PVN and inhibited plasma ACTH responses in these animals. Furthermore, E2-inhibitory effects were mimicked by progesterone (P) alone or in combination with E2. Interestingly, the suppressive central effects of both E2 and P were apparently independent of basal paraventricular corticotropin-releasing hormone (CRH) transcription, since these ovarian steroids did not significantly affect PVN CRH mRNA expression in unstressed rats. These unexpected findings suggested that E2 promotes glucocorticoid hypersecretion in females by additional peripheral (i.e., adrenal) mechanisms. Indeed, E2 markedly enhanced plasma corticosterone responses and adrenal corticosterone content in dexamethasone-blocked OVX rats challenged with varying doses of exogenous ACTH. These results suggest that enhanced adrenal sensitive to ACTH is an important physiological mechanism mediating E2-related glucocorticoid hypersecretion in stressed females.


1978 ◽  
Vol 30 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Robin Stevens ◽  
Ralph Goldstein

Rats treated on the day of birth with progesterone (50 üg) or testosterone pro-pionate (200 üg) or the oil injection vehicle alone were tested in the open-field on four consectuve days at 45 days and 85 days of age. Averages across treatments showed that females ambulated more and reared more than males at both ages, that they groomed more than males at 45 days of age, and defaecated less at 85 days of age. Progesterone treatment significantly reduced defaecation in males at 45 days of age, and reduced grooming in both sexes. At 85 days of age progesterone significantly increased activity in females. Testosterone-treated animals of both sexes groomed significantly less than same-sex controls at 45 days of age, whereas at 85 days of age activity scores were significantly reduced only in females although testosterone treated males were less active on 2 test days and more active on 1. Early postnatal treatment with progesterone appeared to feminise male rats, and testosterone to masculinise female rats. Both hormones also altered the behaviour of opposite sexed rats, indicating that male rats may be further masculinised by exogenous testosterone and female rats further feminised by progesterone. Progesterone may have acted as an anti-androgenic agent by blocking gonadal and adrenal androgens in males and adrenal androgens in females.


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