Biomedical subjects

M F Dallman

Publications and source records attributed to M F Dallman.

At least 127 records · Page 7Linked to original sources

PubMed1986

Some metabolic and behavioral effects of adrenalectomy on obese Zucker rats.

Ten-week-old female obese and lean Zucker rats were given access to three separate macronutrient sources (casein, starch, and lard) for 7 days. They were then either adrenalectomized (ADX) or given a sham operation. Rats were assigned to one of three groups and given a daily injection of either 0, 2, or 10 mg of corticosterone. They continued to select a diet for another 17 days, after which they were killed, and their blood was assayed for corticosterone, adrenocorticotropin hormone (ACTH), insulin, glucose, and triglyceride. Retroperitoneal and parametrial fat depots were excised and sampled for lipoprotein lipase activity, fat cell size, and number. Body composition was also determined. Selection patterns of lean and obese rats were markedly affected by both ADX and corticosterone replacement. All three groups of sham-operated obese rats ate significantly more fat than did sham-operated lean rats. Adrenalectomy significantly reduced fat intakes in both obese and lean rats. Corticosterone therapy restored fat appetites of lean and obese rats in a dose-dependent fashion. In comparison to ADX lean rats, ADX obese rats reduced their normally elevated levels of blood glucose, plasma triglycerides, and insulin to within normal limits. Similarly, adipose cellularity of the ADX obese rats was reduced to that of sham-operated lean rats. Carcass fat was significantly reduced after adrenalectomy. Corticosterone therapy prevented the reduction in a dose-dependent way.

Adipose Tissue↗

PubMed1986

Reset of feedback in the adrenocortical system: an apparent shift in sensitivity of adrenocorticotropin to inhibition by corticosterone between morning and evening.

There is evidence in man and rats that higher circulating levels of glucocorticoids are required to normalize basal unstimulated ACTH levels at the peak of the circadian rhythm than at the trough. To explore this phenomenon, we tested the inhibitory effect of constant levels of corticosterone on plasma ACTH in the morning (AM) and evening (PM) in young male rats implanted with fused pellets of corticosterone-cholesterol at the time of adrenalectomy (ADX+B) and studied 5 days later. There was a marked shift of the plasma corticosterone-ACTH inhibition curve to the right between AM and PM, demonstrating that the efficacy of corticosterone feedback inhibition of ACTH is less in the PM. Comparison of plasma ACTH and corticosterone levels during 24 h in sham-adrenalectomized rats (SHAM-ADX), adrenalectomized rats (ADX), and ADX+B revealed constantly low ACTH in SHAM-ADX, constantly high ACTH in ADX, and biphasic ACTH levels in ADX+B. Corticosterone levels were biphasic in SHAM-ADX and were constant in the other two groups. These results again showed a shift in corticosterone feedback efficacy as a function of the time of day and also suggested that basal ACTH secretion is maintained in the low normal range in intact rats because of the marked diurnal rhythm in corticosterone. The sensitivity of the pituitary ACTH response to exogenous CRF did not change between AM and PM in either intact or ADX+B showing that the shift in feedback sensitivity to corticosterone does not reside in the pituitary. The response of the entire adrenocortical system to histamine stress was shown to be equivalent in both the AM and PM, suggesting that feedback sensitivity of the entire system to corticosterone does not change as a function of the time of day. We conclude from these results that there is an apparent diurnal change in ACTH sensitivity to corticosterone feedback that can be defined operationally as reset. We believe that the site of feedback being tested shifts solely from the pituitary in the AM (at the nadir of the rhythm) to the brain and the pituitary in the PM (at the peak of the rhythm). The lack of the normally high transients of corticosterone that occur in SHAM-ADX rats results in increased brain drive of the pituitary in ADX+B.

Adrenal Cortex↗

PubMed1985

Flavor, forced choice and deprivation affect corticosterone selection by the adrenalectomized rat.

Adrenalectomized rats were given access to corticosterone-supplemented (20 micrograms/ml) and -unsupplemented saline (0.9% NaCl) in two separate bottles and preferences were measured for each. Half of the rats received corticosterone in maple-flavored saline (MAPLE group), while the other half received corticosterone in anise-flavored saline (ANISE group). Each rat also received unsupplemented saline in the alternate flavor. After an initial preference test, preferences were measured again following a period of forced choice (where rats were given the supplemented saline only) and again following a period of deprivation (where rats were given the unsupplemented saline only). All three independent variables (flavor, forced-choice and deprivation) played roles in determining self-administration of corticosterone. Results from the initial preference test demonstrated that both groups preferred the maple-flavored saline whether it contained corticosterone or not. However, consumption of corticosterone-supplemented saline regardless of flavor increased following both forced-choice and deprivation suggesting that the adrenalectomized rats were controlling their corticosterone levels. Strong negative correlations were found between intake of corticosterone-supplemented saline and body weight suggesting that the adrenalectomized rat may be controlling corticosterone levels based on some correlate of body weight.

Adrenal Glands↗

PubMed1985

Corticosterone: narrow range required for normal body and thymus weight and ACTH.

ACTH secretion appears to be under fairly tight negative feedback control by corticosteroids secreted from the adrenal cortex. In these studies we determined the circulating levels of a constant corticosterone signal that best restored body weight gain, thymus weight and ACTH levels to normal in bilaterally adrenalectomized rats given saline to drink. Young male rats were treated at the time of adrenalectomy with subcutaneously implanted pellets of wax or various ratios of corticosterone-cholesterol. Sham-adrenalectomized rats and adrenalectomized rats given corticosterone in the drinking fluid served as comparison groups. Rats were killed 3, 7, or 14 days after adrenalectomy. There was no difference in levels of plasma corticosterone in the morning and in the evening in pellet-implanted rats in contrast to the diurnal variation in the reference groups. Circulating corticosterone levels that best restored body weight, thymus weight, and resting and stress-induced ACTH levels to normal ranged between 4.5 and 7.4 micrograms/dl. Plasma corticosterone levels of 8-11 micrograms/dl were excessive and levels of 2-4 micrograms/dl were not adequate. We conclude that there is a very narrow range of plasma corticosterone compatible with normal growth rate, thymus mass and ACTH secretion. These results reveal the necessity for strict negative feedback regulation of ACTH secretion by corticosteroids.

Adrenocorticotropic Hormone↗

PubMed1985

Acute volume expansion decreases adrenocortical sensitivity to ACTH and angiotensin II.

This study examined the plasma aldosterone and corticosteroid responses to a 60-min infusion of adrenocorticotropin (ACTH) or angiotensin (ANG) II started immediately after an acute isotonic saline volume expansion (0.5 ml . kg-1 . min-1 for 30 min). Five conscious dogs of either sex with exteriorized carotid loops were used in this repeated-design study. Volume expansion per se caused a 10% decrease in hematocrit, a 12.5% decrease in plasma protein, and a 2.7-mmHg increase in central venous pressure with no change in mean arterial pressure, heart rate, or plasma sodium. Volume expansion per se also resulted in significant reductions in vasopressin, plasma renin activity, ACTH, aldosterone, and corticosteroid levels. The aldosterone responses to ACTH and ANG II were significantly inhibited (46-71%) by acute volume expansion. The corticosteroid response to ACTH was 19-29% inhibited by volume expansion. We conclude that acute volume expansion significantly inhibits the adrenocortical sensitivity to its tropic hormones probably via alterations of synergistic factors.

Adrenal Cortex↗

PubMed1985

ACTH and corticosterone secretion in rats following removal of the neurointermediate lobe of the pituitary gland.

Surgical removal of the neurointermediate lobe of the pituitary gland (NIL-X) in the rat resulted in two abnormalities in ACTH secretion: (1) plasma ACTH and corticosterone levels were elevated in the morning and over a 24-hour period compared with levels in control (NIL-C) rats, and (2) although NIL-X and NIL-C rats had acute increases in plasma ACTH and corticosterone of equal magnitude after interoceptive stimuli (hemorrhage, surgery), NIL-X rats demonstrated markedly smaller elevations in plasma levels of these hormones after neurotropic stimuli (noise, novel environment). This subnormal adrenocortical response of NIL-X rats was not due to an impairment in perception of a neurotropic stimulus; these rats had normal latencies to paw licking and to jumping off a heated surface, yet smaller increases in plasma corticosterone after the stimulus. The impairment in ACTH response was not related to stimulus intensity, as NIL-X and NIL-C rats had equal ACTH and corticosterone secretion during both low and high levels of insulin-induced hypoglycemia. NIL-X rats demonstrated a significant elevation in daily water intake, although hematocrit, plasma Na+, K+, osmolality and protein were normal. Significant diurnal rhythms in plasma corticosterone levels and in water intake were maintained as well. The elevated morning plasma ACTH levels, the blunted hormone increases after noise, and the increase in water intake persisted in NIL-X rats 2 months after surgery. These data indicate that removal of the NIL results in (1) chronic elevations in basal ACTH and corticosterone secretion, and (2) chronic impairment in adrenocortical responses to neurotropic stimuli, but not to interoceptive stimuli. The deficit is not due to impaired perceptual capacity nor to the intensity of the stimulus.

Adrenocorticotropic Hormone↗

PubMed1985

Corticotrope response to removal of releasing factors and corticosteroids in vivo.

In the intact rat, adrenalectomy (ADX) is known to result in increased ACTH synthesis, content, and secretion from the anterior pituitary compared with those in the sham-adrenalectomized control. Treatment of adrenalectomized, rats with corticosterone prevents or reverses these changes in ACTH. Because corticosterone is known to act both at the corticotrope and at the level of CRF secretion, it is not clear to what extent the ACTH response to ADX is a result of removal of glucocorticoids from the pituitary per se. To test the role of brain input as well as the role of glucocorticoids on the corticotrope response to ADX, we performed the following experiment. Rats were prepared with anterolateral hypothalamic deafferentations (lesion) which severed CRF and arginine vasopressin cell bodies in the hypothalamus from their axonal endings in the median eminence and posterior pituitary. Control rats were subjected to sham lesions. Two days later, half of the rats in each group were subjected to either ADX or sham ADX; a subgroup of the lesioned rats was provided at the time of adrenal surgery with a constant infusion of rat CRF. Five days later, all rats were killed, and anterior pituitary levels of proopiomelanocortin (POMC) mRNA, ACTH, and protein; plasma ACTH and corticosterone, and adrenal and thymus weights were measured. In sham-lesioned rats, ADX resulted in increases in POMC mRNA, and plasma ACTH of 2.5- and 12-fold, respectively, compared to sham-adrenalectomized controls. In the absence of hypothalamic drive (lesion only), there were no responses of any of these variables to ADX. In lesioned rats driven with CRF, ADX resulted in increases in POMC mRNA and plasma ACTH of 2.2- and 2.6-fold, respectively, compared to sham ADX. After consideration of the three variables indicating ACTH synthesis, storage, and secretion and comparison of the results of ADX vs. sham ADX within and across the sets of animals, we conclude that 1) there is no autonomous response of the corticotrope to ADX; 2) the removal of corticosterone from the anterior pituitary may account for the majority of the effects of ADX on ACTH synthesis; and 3) the normal response to ADX requires secretion of CRF and increased secretion of another ACTH-releasing factor (possibly arginine vasopressin) that causes increased secretion but little synthesis of ACTH.

Adrenal Glands↗

PubMed1985

Closed-loop feedback control of the nyctohemeral rise in adrenocortical system function.

We tested the hypothesis that the increase in adrenocortical system activity is controlled by an error signal generated by the difference between a central reference, or set point, value and some aspect of circulating corticosterone levels in rats maintained on a 12-h light, 12-h dark cycle. The test rats were treated with cyanoketone, an inhibitor that blocks conversion of pregnenolone to progesterone; control rats were treated with vehicle. Test and control rats were fitted with arterial cannulas and, after recovery, continuously collected blood was sampled for plasma corticosterone at 5-min intervals over 2-h periods at five times during the day. Samples were collected at the end of each period for plasma adrenocorticotropin (ACTH). Corticosterone and ACTH levels were similar in the two groups of rats at the nadir (0-2 h after lights-on) and at the peak (0-2 h after lights-off) of the diurnal rhythm. During the time of the maximal diurnal rise in corticosterone (8-10 and 10-12 h after lights-on), test rats had lower mean corticosterone and higher ACTH levels than controls. Infusion of 8 micrograms corticosterone during the 2 h before lights-out did not significantly elevate mean corticosterone levels but decreased end ACTH levels in test rats, whereas similar infusions in control rats resulted in decreased mean corticosterone levels and no change in end ACTH. We conclude that the nyctohemeral rise in ACTH is driven by an error signal resulting from the difference between a central set point value and some aspect of plasma corticosterone levels.

Adrenal Cortex↗

PubMed1984

The pituitary-adrenal response to stress in the iron-deficient rat.

This study was designed to determine the ACTH-corticosterone response to two types of stress in relation to the daily rhythm of food and water intake in the iron-deficient rat. Rats were fed diets containing 2, 10 or 50 mg iron/kg diet between weaning at 21 days and the stress experiments at 38 or 42 days of age. The two iron-deficient diets (2 and 10 mg iron/kg) resulted in mean hemoglobin concentrations of about 6.0 and 8.5 g/dl, respectively, in contrast to about 12.5 g/dl in the control group receiving 50 mg iron/kg diet. Food and water consumption followed the normal nocturnal pattern, irrespective of iron intake. ACTH and corticosterone showed the normal baseline peaks at the 2000 hour lights-out point in all groups. Responses to handling and placement into another cage were similar in most respects but suggested an inappropriately low corticosterone response despite high ACTH values only at the 2000 hour point. However, there was no evidence of similar differences in response to the more potent stress of an i.p. injection of histamine 1 mg/100 g body weight. In contrast to the reports of more clear-cut effects of iron deficiency on norepinephrine, the changes in ACTH and corticosterone response to stress seem relatively modest.

Adrenocorticotropic Hormone↗

PubMed1984

Interaction between stimulus intensity and corticosteroid feedback in control of ACTH.

These studies were performed to examine the relationship between stimulus intensity and corticosteroid feedback on ACTH secretion. We have measured the ACTH responses in five dogs to each of three levels of hypoglycemia induced by injection of three doses of insulin after production of each of four levels of corticosteroid feedback induced by the infusion of saline or three rates of ACTH. Both the peak and integrated ACTH responses were related to the degree of hypoglycemia in saline-infused dogs (P less than 0.01). ACTH infusions did not affect the hypoglycemia induced by insulin; however, the lower two infusion rates (20 and 50 ng/min for 40 min) inhibited the peak ACTH responses to hypoglycemia by mean values of 45 and 75%, respectively, and the integrated ACTH responses by about 60 and 90%, respectively. The high infusion rate of ACTH (500 ng/min for 40 min) abolished the subsequent ACTH responses to hypoglycemia (103% inhibition). Therefore, the degree (%) of inhibition was the same for a given prior corticosteroid level at all intensities of hypoglycemia. The plasma ACTH response was a function of both stimulus intensity and prior corticosteroid levels and was proportional to the stimulus intensity divided by the feedback dose. Thus, corticosteroids exert a modulatory rather than a simple subtractive effect on the secretion of ACTH.

Adrenal Cortex Hormones↗

PubMed1984

Viewing the ventromedial hypothalamus from the adrenal gland.

The relationships among food intake, insulin secretion, and adrenocortical function are reviewed. It is hypothesized that a major role of structures in, or passing through, the ventromedial hypothalamus is to inhibit food intake, insulin secretion, and adrenocortical function during the day (in the nocturnally active rat) and that this activity is normally driven by elements within the suprachiasmatic nuclei. Lesions of the ventromedial hypothalamus of rats result in nonrhythmic food intake, hyperinsulinemia, nonrhythmic adrenocortical function, and obesity. Adrenalectomy prevents or reverses the effects of lesions of the ventromedial hypothalamus on food intake, insulin secretion, and obesity, and corticosteroid replacement restores them. Because the actions of corticosteroids are both time- and dose-dependent, it is proposed that the effects of the tonic levels of corticosteroids observed after lesions of the ventromedial hypothalamus are to augment the hyperphagia, hyperinsulinemia, and substrate flow into fat to a greater extent than would occur if there were a normal circadian rhythm in adrenocortical function.

Adipose Tissue↗

PubMed1984

Renin and ACTH responses to hypercapnia and hypoxia after chronic carotid chemodenervation.

We studied the effect of chronic carotid body denervation on renin (plasma renin activity, PRA), adrenocorticotropin (ACTH), blood pressure, and hematocrit responses to acute normocapnic (arterial CO2 partial pressure, PaCO2, 35 Torr) and hypercapnic (PaCO2, 65 Torr) hypoxia (arterial O2 partial pressure, PaO2, 31 Torr) in five anesthetized, artificially ventilated dogs. Animals were studied at least 3 days before and again at least 10 days after carotid body denervation (bilateral carotid sinus nerve resection). Increases in PRA during hypercapnic normoxia [21.8 +/- 6.4 ng angiotensin I (ANG I) X ml-1 X 3 h-1] and normocapnic hypoxia (13.3 +/- 4.2 ng ANG I X ml-1 X 3 h-1) were not attenuated by carotid body denervation. Increases in ACTH during normocapnic hypoxia (117 +/- 34 pg/ml) were attenuated but not eliminated by carotid body denervation; the increase in ACTH during hypercapnic hypoxia (295 +/- 93 pg/ml) was not attenuated by carotid body denervation. Both the blood pressure and hematocrit responses to normocapnic and hypercapnic hypoxia were attenuated by carotid body denervation. We concluded that 1) the renin response to hypercapnia and hypoxia is not a carotid chemoreflex, 2) the ACTH response to hypoxia is partially a carotid chemoreflex, and 3) blood pressure and hematocrit responses to hypoxia are primarily carotid chemoreflexes.

Adrenal Cortex Hormones↗

PubMed1984

Corticosteroid inhibition of ACTH secretion.

Corticosteroid feedback inhibits the brain-hypothalamo-pituitary units of the adrenocortical system. Naturally occurring corticosteroids may have their primary actions in vivo at brain and hypothalamic sites of feedback, whereas synthetic glucocorticoids that do not bind to transcortin may act primarily on corticotropes and regions of brain outside the blood-brain barrier. There appear to be three major time frames of corticosteroid action: fast, intermediate and slow. These time frames probably are the consequence of three separate mechanisms of corticosteroid action at feedback-sensitive sites. The rapidity of occurrence of fast feedback is not compatible with a nuclear site of corticosteroid action, and protein synthesis is not required. The action of CRF on ACTH release may be inhibited by a rapid effect of corticosteroids at the cell membrane. Since stimulated, but not basal, ACTH and CRF release are inhibited in vitro, the corticosteroids may inhibit some event in stimulus-secretion coupling (e.g., cAMP production). Intermediate feedback also decreases ACTH release in response to stimulation of the corticotrope, but does not affect ACTH synthesis; CRF synthesis and release both appear to be affected by the intermediate corticosteroid action. The mechanism of intermediate feedback requires the presence of a protein whose synthesis is corticosteroid-dependent; however, the role of this protein is unknown. Intermediate feedback, like fast feedback, apparently does not involve inhibition of total ACTH stores or the releasable pool of ACTH since basal secretion of ACTH is also not inhibited in vitro within this time domain. On the other hand, slow feedback apparently involves the classical genomic steroid mechanism of action; slow feedback reduces pituitary ACTH content by decreasing levels of mRNA encoding for POMC, the ACTH precursor molecule. Slow feedback, therefore, inhibits basal as well as stimulus induced ACTH secretion. Corticosteroid-induced inhibition of basal ACTH secretion has been shown to occur within 2 h in vivo but not in vitro. The time course and sensitivity of this feedback effect is different than that demonstrated for stimulus induced secretion. This difference suggests that basal secretion is activated by different pathways to (CRF and) ACTH secretion. There is some evidence that suggests that whereas comparator elements are not reset during stress, a comparator element is reset during the course of the circadian rhythm so that different basal levels of steroid are achieved.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

PubMed1984

Feedback inhibition of adrenocorticotropin and vasopressin responses to hypoxia by physiological increases in endogenous plasma corticosteroids in dogs.

We examined the influence of increases in plasma corticosteroids produced by ACTH infusion on subsequent ACTH and vasopressin (AVP) responses to hypoxia in anesthetized dogs. Basal and stimulated ACTH levels were inhibited by increases in corticosteroids. Moderate increases in corticosteroids (5.2 micrograms/dl) caused a 50% reduction in the subsequent integrated ACTH response to hypoxia. Maximal increases in corticosteroids eliminated the integrated ACTH response to hypoxia. In addition, AVP responses to hypoxia were attenuated by prior maximal elevations in corticosteroids. Physiological elevation of corticosteroids inhibits subsequent ACTH and AVP responses to hypoxia.

Adrenal Cortex Hormones↗

PubMed1984

The effects of corticotropin-releasing factor on adrenocorticotropin secretion from perifused pituitaries in vitro: rapid inhibition by glucocorticoids.

The effect of synthetic corticotropin-releasing factor (CRF) and glucocorticoids on ACTH secretion from rat anterior pituitaries was examined in vitro. Pituitaries were cut into 12 fragments and perifused at 37 C with a modified Krebs buffer. CRF produced a rapid (1-min), Ca2+-dependent rise in ACTH secretion, with a half-maximally effective concentration of about 1 nM. ACTH secretion declined after 90 min of continuous perifusion with CRF. In vivo, glucocorticoids can inhibit stress-induced ACTH secretion with a latency of a few seconds. In our experiments, coperifusion with 10(-7) M cortisol, corticosterone, or dexamethasone, but not cortisone, inhibited the effect of CRF by nearly 50%. The latency of the inhibition was between 10 and 20 min, and the inhibition persisted for as long as the steroid was present. Basal secretion was unaffected by steroid treatment for 30 min. These results indicate that rapid inhibition of stimulated ACTH secretion can occur at the level of the pituitary in vitro, but that the feedback differs from that observed in vivo in terms of the longer latency and the persistence of the response.

Adrenocorticotropic Hormone↗

PubMed1983

Vasopressin, ACTH, and corticosteroids during hypercapnia and graded hypoxia in dogs.

We examined the interaction of graded hypoxia and hypercapnia on stimulation of vasopressin (AVP), ACTH, and corticosteroids in nonsurgically stressed, pentobarbital-anesthetized, gallamine-paralyzed ventilated dogs. Partial pressure of O2 in arterial blood (PaO2) levels of approximately 26-29, 38-41, 54-57, and 83-88 Torr were achieved by altering the fractional concentration of O2 in dry inspired gas with a normocapnic (PaCO2, 35 Torr) and hypercapnic (PaCO2, 59 Torr) background. Normocapnic hypoxia produced a PaO2-dependent increase in AVP, ACTH, and corticosteroids. The threshold PaO2 for AVP was lower (approximately 35 Torr) than for ACTH (approximately 45 Torr). AVP, ACTH, and corticosteroids at all PaO2 levels were higher during hypercapnia. In addition, an ACTH and corticosteroid dose-response correlation estimated the threshhold ACTH to be 20-30 pg/ml. The PaO2-dependent hormone increases and the augmentation of these relationships by hypercapnia are consistent with a peripheral chemoreceptor-mediated reflex. In addition, hypoxia and hypercapnia did not seem to alter the high sensitivity of the adrenal cortex for ACTH.

Adrenal Cortex Hormones↗

PubMed1983

Vasopressin, ACTH, and blood pressure during hypoxia induced at different rates.

We decreased arterial PO2 at three different rates and measured blood pressure (BP), vasopressin (AVP), ACTH, and corticosteroid levels in nonsurgically stressed, anesthetized, paralyzed dogs. PaO2 was lowered to 28 Torr in 2 (fast), 10 (moderate), and 20 min (slow). The fast dPO2/dt produced a large spike in BP. Increases in AVP, ACTH, and corticosteroids were similar regardless of the dPO2/dt. When the spike in BP during the fast dPO2/dt was prevented with nitroprusside, hormone levels increased more quickly and were higher during the first 20-30 min of hypoxia. By 60 min, hormone levels were not different between experiments. The data suggest that 1) faster decreases in PO2 produce larger increases in BP, 2) increases in AVP, ACTH, and corticosteroids are primarily sensitive to the level of steady-state PaO2, and 3) increases in BP inhibit stress-induced increases in AVP and ACTH.

Adrenal Cortex Hormones↗

PubMed1983

Effects of housing and chronic cannulation on plasma ACTH and corticosterone in the rat.

Effects of housing and cannulation on plasma ACTH and corticosterone levels were evaluated to validate a method for obtaining repeated blood samples for ACTH from conscious rats. Resting morning, evening, or noise-stimulated (4 min of metal rattling) levels of plasma ACTH or corticosterone obtained by decapitation were similar in rats housed alone or in pairs. Individually housed, cannulated rats had slightly elevated morning levels of plasma ACTH and corticosterone, but the evening and noise-stimulated increases in hormone levels were similar to those in unoperated, decapitated rats. A hemorrhage stimulus administered on separate days to cannulated rats evoked highly replicable elevations in plasma ACTH and corticosterone. These results demonstrate that 1) ACTH and corticosterone secretion are similar in rats housed alone versus in pairs, and 2) long-term cannulation permits multiple intra-animal comparisons of basal and acutely stimulated plasma ACTH and corticosterone levels that are useful reflections of those measured in decapitated rats.

Adrenocorticotropic Hormone↗