Mechanism of restoration of ACTH release in rats with long-term lesions of the paraventricular nuclei

1986 ◽  
Vol 111 (1) ◽  
pp. 75-82 ◽  
Author(s):  
J. Dohanics ◽  
G. Kapócs ◽  
T. Janáky ◽  
J. Z. Kiss ◽  
G. Rappay ◽  
...  
Keyword(s):  
Median Eminence ◽  
Plasma Concentrations ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Paraventricular Nuclei ◽  
Basal Plasma ◽  
Corticosterone Response ◽  
Intact Rats ◽  
Acth Release

ABSTRACT The effects of lesions in the paraventricular nucleus (PVN) on the adrenocortical response to ether stress were investigated in neurohypophysectomized and intact rats. During the first 4 days after placement of lesions in the PVN, the corticosterone response to ether stress was almost completely inhibited. It then gradually increased and, within 4–6 weeks of surgery, was restored to about 60% of that in sham-operated rats. Basal plasma concentrations of corticosterone were low in rats after placement of lesions in the PVN and/or after neurointermediate lobectomy (NILX). Corticosterone responses to ether stress were similar in groups submitted to PVN lesions and/or NILX, and lower than those in the appropriate sham-operated groups. In all lesioned groups, plasma ACTH concentrations after a combination of stressors (ether plus laparotomy) were also lower than those in the sham-operated groups. Six weeks after lesioning of the PVN, immunoreactive rat corticotrophin-releasing factor-41 (rCRF-41) concentrations in stalk-median eminence (SME) extract fell to about 5% of that in sham-operated rats, while immunoreactive arginine vasopressin (AVP) concentrations did not change. Immunohistochemistry revealed a substantial decrease in rCRF-41 immunostaining of the median eminence 6 weeks after lesioning of the PVN, though randomly located clusters of stained terminals were still seen in the whole rostro-caudal extent of the median eminence. A mixture containing synthetic rCRF-41 and AVP, in proportions similar to those in SME extracts from sham-operated rats, caused significantly less release of ACTH from anterior pituitary cell cultures than did SME extracts from sham-operated rats. Extracts of SME from PVN-lesioned rats released as much ACTH as a mixture containing synthetic rCRF-41 and AVP in proportions similar to those in the SME extracts from PVN-lesioned rats. Extracts of SME from either PVN-lesioned or sham-operated rats did not cause a significant increase in the amount of ACTH released when preincubated with antisera to both rCRF-41 and AVP. It is suggested that (1) the restoration of the adrenocortical reponse to ether stress, evident within a few days of placement of lesions in the PVN, occurs independently of neurohypophysial function; (2) the full corticosterone and ACTH response to ether or ether plus laparotomy stress requires not only an intact PVN but also an intact neurointermediate lobe; (3) SME extracts from sham-operated rats contain a factor(s) with the ability to potentiate the ACTHreleasing effect of rCRF-41 and AVP; and (4) the ACTH-releasing activity of SME extract obtained from rats with long-term PVN lesions is probably due to its remaininJ content of rCRF-41 and AVP. J. Endocr. (1986) 111, 75–82

Effects of paraventricular lesions on stimulated ACTH release and CRF in stalk-median eminence of the rat

1981 ◽  
Vol 240 (4) ◽  
pp. E441-E446 ◽  
Author(s):  
G. B. Makara ◽  
E. Stark ◽  
M. Karteszi ◽  
M. Palkovits ◽  
G. Rappay
Keyword(s):  
Median Eminence ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Surgical Trauma ◽  
Acth Level ◽  
Plasma Acth ◽  
Medial Basal Hypothalamus ◽  
Plasma Acth Level ◽  
Basal Plasma ◽  
Corticosterone Response

The effects of destroying the paraventricular nucleus (PVN) of the rat hypothalamus on pituitary-adrenal function were studied. Four days after PVN lesions were placed with a rotating knife, the basal plasma corticosterone level was normal, but the corticosterone response to electrical stimulation of the medial basal hypothalamus, surgical trauma, and ether-venesection stress was significantly inhibited. Four and 8 days after PVN lesioning and adrenalectomy, the basal plasma ACTH level was lower, and the rise of plasma ACTH level elicited by a 3-min ether inhalation was significantly smaller than in the adrenalectomized controls. Corticotropin-releasing factor (CRF) activity in the stalk-median eminence extracts from PVN-lesioned rats was significantly less than in the control extracts. The weight of the adrenals was decreased by both 2 and 4 wk after PVN destruction, and 2 wk after hemiadrenalectomy, the compensatory adrenal hypertrophy was inhibited. The plasma corticosterone response to ether-venesection stress was inhibited only temporarily because it returned to normal by the end of the 4th postoperative week. The results are consistent with the hypothesis that a substantial portion of CRF-containing fibers in the stalk-median eminence region either originate from or run though the PVN or its immediate vicinity.

Adrenal and gonadal function in hypothyroid adult male rats

1997 ◽  
Vol 152 (1) ◽  
pp. 147-154 ◽  
Author(s):  
A Tohei ◽  
M Akai ◽  
T Tomabechi ◽  
M Mamada ◽  
K Taya
Keyword(s):  
Adult Male ◽  
Functional Relationship ◽  
Plasma Concentrations ◽  
Gonadal Hormones ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Male Rats ◽  
Plasma Acth ◽  
Corticosterone Release ◽  
Acth Release

Abstract The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouracil-treated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH. Journal of Endocrinology (1997) 152, 147–154

Effect of long-term infusion of ovine corticotrophin-releasing factor in the immature ovine fetus

1986 ◽  
Vol 111 (3) ◽  
pp. 469-475 ◽  
Author(s):  
E. M. Wintour ◽  
R. J. Bell ◽  
R. S. Carson ◽  
R. J. MacIsaac ◽  
G. W. Tregear ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Maternal Plasma ◽  
In Utero ◽  
Premature Delivery ◽  
Jugular Veins ◽  
Plasma Progesterone ◽  
Fetal Plasma ◽  
Corticotrophin Releasing Factor ◽  
Ovine Fetus

ABSTRACT Synthetic ovine corticotrophin-releasing factor (oCRF) was infused continuously into the jugular veins of six ovine fetuses for 5–11 days. Two fetuses receiving 0·1 and 1·0 μg oCRF/h from gestational days 134 and 135 respectively, lambed prematurely on days 141 and 140 respectively. Three out of four fetuses receiving oCRF at 2·4 μg/h, from 125 days of gestation, delivered spontaneously at 131, 131 and 136 days, whilst one died in utero at 132 days. Two fetuses receiving vehicle only or oCRF intra-amniotically, were born at 148 and 145 days respectively, whilst six fetuses chronically cannulated but not infused were born at 149·8 ±2·1 (s.d.) days. In ewes lambing at term, maternal plasma progesterone concentrations were 41·4±11·4 (s.e.m.; n = 5), 28·8±7·8 (n = 6), 17·1 ±4·8 (n = 5) and 7·9± 1·1 (n = 4) nmol/l on 3, 2, 1 and 0 days respectively before the lambs were born. No such decrease in maternal plasma progesterone concentrations was seen in the oCRF-infused fetuses. Fetal plasma concentrations of immunoreactive ACTH were maintained above normal in oCRF-infused fetuses, but some desensitization to bolus oCRF injections occurred in these fetuses. Four of the five fetuses born prematurely were sufficiently mature to survive, being able to stand, breathe and suckle. It is concluded that continuous oCRF infusions into immature fetuses can accelerate maturation of a number of organs and systems culminating in the premature delivery of viable lambs. J. Endocr. (1986) 111, 469–475

Corticotrophin-releasing peptides in rat hypophysial portal blood after paraventricular lesions: a marked reduction in the concentration of corticotrophin-releasing factor-41, but no change in vasopressin

1990 ◽  
Vol 125 (2) ◽  
pp. 175-183 ◽  
Author(s):  
F. A. Antoni ◽  
G. Fink ◽  
W. J. Sheward
Keyword(s):  
Median Eminence ◽  
Feedback Inhibition ◽  
Portal Blood ◽  
Corticotrophin Releasing Factor ◽  
Paraventricular Nuclei ◽  
Oxytocin Release ◽  
Male Wistar Rats ◽  
Hypophysial Portal ◽  
Supraoptic Nuclei

ABSTRACT Previous data show that corticotrophin-releasing factor-41 (CRF-41), arginine vasopressin (AVP) and oxytocin are released into hypophysial portal blood. It has been presumed that the CRF-41 originates mainly from parvicellular neurones of the paraventricular nuclei (PVN); however, AVP and oxytocin could also be derived as a consequence of preterminal release from magnocellular projections to the neurohypophysis. The latter has been suggested to be the case for AVP as assessed by studies of the median eminence in vitro. Here we have investigated the source of CRF-41, AVP and oxytocin in hypophysial portal blood of adult male Wistar rats 8–10 days after surgical lesioning of the PVN. In PVN-lesioned animals the output of CRF-41 into hypophysial portal blood was reduced by about 90%, and that of oxytocin by about 40%: however, the output of AVP into portal blood was reduced only by about 10%. The release of AVP into portal blood increased after adrenalectomy; this increased release could be returned to normal by treatment with dexamethasone. No change of AVP release occurred after adrenalectomy in animals in which the PVN had been lesioned. These results show (i) that most of the CRF-41 released into hypophysial portal blood is derived from the PVN, (ii) that in PVN-lesioned animals AVP and oxytocin release remains at near normal or 60% of normal respectively, suggesting that a substantial amount of both neuropeptides in portal blood is derived as a consequence of preterminal release from supraoptic nuclei projections in the median eminence, and (iii) that glucocorticoid feedback inhibition of AVP release is exerted at the level of the PVN. Journal of Endocrinology (1990) 125, 175–183

Dexamethasone inhibits ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), and oCRF + AVP stimulated release of ACTH during the last third of pregnancy in the sheep fetus

1987 ◽  
Vol 65 (6) ◽  
pp. 1186-1192 ◽  
Author(s):  
Laurie J. Norman ◽  
John R. G. Challis
Keyword(s):  
Negative Feedback ◽  
Arginine Vasopressin ◽  
Late Pregnancy ◽  
Feedback Effect ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Corticotrophin Releasing Factor ◽  
Basal Release ◽  
Sheep Fetus ◽  
Acth Release

We examined the hypothesis that in fetal sheep during late pregnancy exogenous glucocorticoids might affect differentially the pituitary response, measured as changes in plasma ACTH concentrations, to the systemic administration of ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), or oCRF + AVP. At d 113–116 of pregnancy, equimolar injections of oCRF and AVP given separately provoked similar significant increases in plasma ACTH; the change in ACTH over basal values was significantly greater than the sum of the two separate responses when AVP + oCRF were given together. Exogenous dexamethasone did not affect basal ACTH concentrations, but suppressed significantly the responses to oCRF, AVP, and oCRF + AVP. At d 126–130, there was a significant ACTH response to CRF alone and to AVP + oCRF, but not to AVP alone. The response during the first 30 min postinjection to oCRF was significantly less than that to AVP + oCRF. Plasma Cortisol rose after each peptide injection. Exogenous dexamethasone suppressed both basal and stimulated responses to each peptide. At the amounts injected, there was no significant ACTH or Cortisol response to oCRF, AVP, or oCRF + AVP at d 136–140, but dexamethasone suppressed basal ACTH and Cortisol concentrations at this time. We conclude that stimulated, but not basal, release of ACTH is subject to the negative feedback effect of exogenous glucocorticoid by d 113–116 of gestation in fetal sheep. Both basal and stimulated release of ACTH and Cortisol are suppressed after d 125. At the amount of exogenous dexamethasone given, oCRF, AVP, and oCRF + AVP-stimulated responses are affected similarly. Our results suggest different controls of basal and stimulated ACTH release from the pituitary at d 113–116 of gestation. Our findings would be consistent with the pituitary as a level of action for the negative feedback effect of corticosteroids on stimulated ACTH release throughout the last third of pregnancy in fetal sheep.

Effects of corticosterone on the secretion of corticotrophin-releasing factor, arginine vasopressin and oxytocin into hypophysial portal blood in long-term hypophysectomized rats

1991 ◽  
Vol 129 (1) ◽  
pp. 91-98 ◽  
Author(s):  
W. J. Sheward ◽  
G. Fink
Keyword(s):  
Arginine Vasopressin ◽  
Portal Blood ◽  
Blood Collection ◽  
Continuous Administration ◽  
Feedback Effects ◽  
Corticotrophin Releasing Factor ◽  
Hypophysectomized Rats ◽  
Hypophysial Portal ◽  
Intact Rats

ABSTRACT To investigate the feedback effects of corticosterone on the secretion of corticotrophin-releasing factor-41 (CRF-41), oxytocin and arginine vasopressin (AVP), hypophysial portal vessel blood was collected from control (intact) and long-term (6–8 weeks) hypophysectomized rats. In preliminary experiments in rats anaesthetized with urethane, long-term hypophysectomy resulted in a significant increase in the secretion of oxytocin and AVP; the hypothalamic contents of oxytocin and AVP were also increased in comparison with pituitary-intact rats. In long-term hypophysectomized rats anaesthetized with sodium pentobarbitone, but not with urethane, the output of CRF-41 into portal blood was increased twofold in comparison with that in control rats. In long-term hypophysectomized rats anaesthetized with pentobarbitone, the i.v. infusion of corticosterone (7·2 nmol/min) for a 2 h period of portal blood collection did not alter the secretion of CRF-41, oxytocin or AVP into portal blood; however, the secretion of CRF-41 and, to a lesser extent, AVP was significantly reduced in hypophysectomized rats by continuous corticosterone replacement, by a pellet of corticosterone implanted s.c. for 5 days before portal blood collection. These results confirm that the secretion of CRF-41 is differently affected by the anaesthetics urethane and pentobarbitone, and in long-term hypophysectomized rats show (i) that there were no apparent feedback effects of corticosterone infusion over a 2 h period on the secretion of any of the peptides studied, (ii) that late delayed feedback effects of continuous administration of corticosterone are mediated by a reduction in CRF-41 and AVP output, and (iii) that corticosterone has no effects on oxytocin secretion into portal blood. Journal of Endocrinology (1991) 129, 91–98

scholarly journals Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in hypothyroid male rats as estimated with push-pull perfusion

1998 ◽  
Vol 156 (2) ◽  
pp. 395-400 ◽  
Author(s):  
A Tohei ◽  
G Watanabe ◽  
K Taya
Keyword(s):  
Drinking Water ◽  
Median Eminence ◽  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Male Rats ◽  
Releasing Hormone ◽  
In Vivo Release ◽  
The Relationship ◽  
Acth Release

The relationship between hypothyroidism and disturbance of the hypothalamo-hypophysial-adrenal axis was investigated using adult male rats. Hypothyroidism was produced by administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Hypothyroidism decreased adrenal weights to 57% of controls and plasma concentrations of corticosterone to 48% of controls. The changes in the weight of adrenals recovered to control levels by administration of thyroxine. The pituitary responsiveness to corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) for ACTH release markedly increased in hypothyroid rats as compared with euthyroid rats. In vivo release of CRH and AVP in median eminence significantly increased in hypothyroid rats as compared with euthyroid rats. There were no significant differences in hypothalamic concentrations of CRH and AVP. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH mediated by increases in synthesis of CRH and AVP in the hypothalamus.

Inhibition by dexamethasone of arginine vasopressin and ACTH responses to insulin-induced hypoglycemia and cigarette smoking in normal men

1990 ◽  
Vol 123 (5) ◽  
pp. 487-492 ◽  
Author(s):  
P. Chiodera ◽  
V. Coiro
Keyword(s):  
Cigarette Smoking ◽  
Plasma Concentrations ◽  
Peak Level ◽  
Inhibitory Effect ◽  
Dexamethasone Treatment ◽  
Plasma Acth ◽  
The Mean ◽  
Normal Men ◽  
Circulating Levels ◽  
Acth Release

Abstract. Glucocorticoids are known to inhibit the AVP response to osmotic and hemodynamic stimuli in humans. In the present study, we examined whether the AVP response to other primary stimuli, such as insulin-induced hypoglycemia and cigarette smoking was sensitive to inhibition by dexamethasone. The plasma ACTH responses were also measured. Twenty-four normal men were randomly divided into 3 groups of 8 subjects. One group was tested with insulin (0.15 IU/kg in an iv bolus) and another group with cigarette smoking (2 non-filter cigarettes smoked in succession within 10 min) with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin or smoking). The third group was tested with dexamethasone alone (2 or 4 mg in an iv bolus). The administration of dexamethasone (2 or 4 mg) alone did not modify the circulating levels of AVP and ACTH at any time during the next hour. The hypoglycemic response to insulin was similar regardless of dexamethasone treatment. AVP rose sharply in response to both hypoglycemia and smoking, reaching mean peak levels at 45 and 30 min, respectively. After both stimuli, the mean peak levels of AVP were 2.25 times higher than baseline. Pretreatment with dexamethasone (2 or 4 mg) significantly decreased the AVP responses to both hypoglycemia and cigarette smoking. Following pretreatment with dexamethasone (2 or 4 mg) the AVP increments in response to hypoglycemia or cigarette smoking were only 1.7 times higher than baseline. The plasma concentrations of ACTH were strikingly increased by hypoglycemia. The mean peak level was 3.5 times higher than baseline and was reached at 45 min. Pretreatment with dexamethasone (2 or 4 mg) significantly reduced hypoglycemia-induced ACTH increase, with a mean peak response 2.8 times higher than baseline. Cigarette smoking significantly increased the plasma ACTH concentrations. The mean peak level was observed at 20 min and was 1.3 times higher than baseline. The ACTH response to smoking was not significant following pretreatment with dexamethasone (2 or 4 mg). These data show a partial inhibitory effect of dexamethasone on hypoglycemia-and cigarette smoking-stimulated AVP secretion. In addition, the data show suppression by dexamethasone of the ACTH response to cigarette smoking and confirm previous observations of a partial inhibition by glucocorticoids of hypoglycemia-induced ACTH release.

Isolated ACTH deficiency accompanied by 'primary hypothyroidism' and hyperprolactinaemia

1983 ◽  
Vol 104 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Tadayoshi Yoshida ◽  
Tetsuya Arai ◽  
Jinpei Sugano ◽  
Hiroshi Yarita ◽  
Hideo Yanagisawa
Keyword(s):  
Pituitary Gland ◽  
Primary Hypothyroidism ◽  
Hormonal Changes ◽  
Plasma Acth ◽  
Isolated Acth Deficiency ◽  
Acth Deficiency ◽  
Corticotrophin Releasing Factor ◽  
Lysine Vasopressin ◽  
Before And After

Abstract. A 55 year old man with isolated ACTH deficiency is reported. The lesion would appear to be located in the pituitary gland since plasma ACTH and cortisol did not respond to lysine vasopressin and corticotrophin releasing factor (CRF). A fall in T4, a rise in basal values of TSH, prolactin (Prl), LH and FSH, excessive responses of TSH and Prl to TRH, and hyperreactive responses of LH and FSH to LRH were observed. These hormonal changes were examined before and after administration of cortisol. The abnormality in these hormones might be caused by deficiency of long-term glucocorticoid.

Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

1994 ◽  
Vol 141 (3) ◽  
pp. 497-503 ◽  
Author(s):  
P J Larsen ◽  
J D Mikkelsen ◽  
D Jessop ◽  
S L Lightman ◽  
H S Chowdrey
Keyword(s):  
Hpa Axis ◽  
Restraint Stress ◽  
Acute Stress ◽  
Monosodium Glutamate ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Acute And Chronic Stress ◽  
Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

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