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M F Dallman

Publications and source records attributed to M F Dallman.

At least 145 records · Page 8Linked to original sources
PubMed1983

Integral as well as proportional adrenal responses to ACTH.

To characterize adrenal responses to ACTH, conscious dogs were infused for 40 min with normal saline or 20-1,500 ng/min alpha-ACTH. Plasma ACTH and corticosteroid levels were measured during the infusion and for 80 min after the end of the infusion. Half-maximal plateau corticosteroid responses were achieved with ACTH levels of 105 pg/ml (23 pM); a maximal plateau corticosteroid response (10.2 micrograms/100 ml) resulted from ACTH levels greater than 335 pg/ml (74 pM). When levels of ACTH between 335 and 3,000 pg/ml were achieved during the 40-min infusion, the duration of maximal corticosteroid levels was prolonged beyond the duration of the ACTH infusion. Plasma ACTH concentration decreased after the end of the infusion with a half-disappearance time of 3.6 +/- 0.2 min, but plasma corticosteroid concentrations and cortisol and corticosteroid secretory rates remained at or above the plateau secretory rates during the infusion and for about 80 min after the end of an infusion of 1,000 ng ACTH/min. When the total corticosteroid responses to the ACTH infusions were estimated, the relationship between the total corticosteroid response and the logarithm of the ACTH concentration was linear for 80-3,000 pg ACTH/ml.

Adrenal Cortex Hormones↗
PubMed1983

Feedback inhibition of adrenocorticotropic hormone by physiological increases in plasma corticosteroids in conscious dogs.

We have tested the effect of physiological increases in plasma corticosteroids in conscious dogs on the levels of basal and hypoglycemia-stimulated adrenocorticotropic hormone (ACTH) 2 h later. Increases in plasma corticosteroids, produced by infusion of alpha-1-24 ACTH or corticosteroids for 40 min, suppressed basal and stimulated ACTH levels. The magnitude of inhibition produced by an increase in plasma corticosteroids induced by the infusion of ACTH was equivalent to the inhibition produced by the same increase in plasma corticosteroids induced by corticosteroid infusion. The infusions did not affect basal plasma glucose concentrations or the decrease in plasma glucose concentrations after administration of 0.1 U insulin/kg. Basal ACTH concentration was less sensitive than hypoglycemia-stimulated ACTH concentration to corticosteroid-induced suppression. Basal and stimulated secretion were significantly inhibited in all dogs after approximately half-maximal increases in plasma corticosteroids; maximum inhibition occurred after maximal increases in plasma corticosteroids. Therefore, physiological increments in plasma corticosteroids, similar to those produced by acute stress, are effective suppressors of subsequent stress-induced ACTH secretion.

Adrenal Cortex Hormones↗
PubMed1983

Inhibition of the adrenocorticotropin and corticosteroid responses to hypoglycemia after prior stress.

We have tested the efficacy of prior stress-induced increases in corticosteroids on inhibition of the ACTH response to hypoglycemia induced 2 h later. Five dogs were studied in each of five experiments. In each experiment, there were two stimulus periods; in the first, 5% dextrose, 3 or 10 micrograms/kg X min nitroprusside, or 0.05 or 0.10 U/kg insulin was administered, and in the second, 0.10 U/kg insulin was administered. Whereas prior infusion of 5% dextrose did not affect the subsequent ACTH response to 0.10 U/kg insulin, prior stimulation of the pituitary-adrenal axis had a significant effect on the subsequent ACTH response to 0.10 U/kg insulin. The integrated ACTH response to hypoglycemia was significantly reduced by prior stimulation by either 10 micrograms/kg/min nitroprusside or 0.10 U/kg insulin, although the intensity of the hypoglycemia during the second stimulus period was not altered by any of the prior stimuli. Overall, the magnitude of the suppression of the pituitary-adrenal response to hypoglycemia was significantly related to the increase in plasma corticosteroids produced by the first stimulus, and was consistent with the degree of corticosteroid feedback inhibition of ACTH observed in previous studies after ACTH or corticosteroid infusion. Therefore, we conclude that prior stimulation of the hypothalamo-pituitary-adrenal axis of conscious dogs by hypotension or hypoglycemia inhibits subsequent responses in proportion to the corticosteroid feedback signal produced.

Adrenal Cortex Hormones↗
PubMed1983

Relationships among adrenal weight, corticosterone, and stimulated adrenocorticotropin levels in rats.

Based on results of previous studies, we tested the hypothesis that increased adrenal weight in the absence of increased corticosterone secretion would inhibit the magnitude of the ACTH response to ether vapor. Adrenal hypertrophy was induced by treatment of rats for 3 days with aminoglutethimide, cyanoketone, or metyrapone, three agents that act to inhibit enzymes required for corticosterone synthesis. On the fourth day, resting plasma ACTH and corticosterone levels were normal; however, the logarithm of the ACTH response to ether was directly related to total adrenal weight. This result did not support the hypothesis. Unilateral adrenalectomy and treatment with cyanoketone resulted in total adrenal weight equivalent to that of control rats bearing two adrenals. Resting ACTH levels were normal, but stimulated ACTH was significantly greater in these rats than in controls or in rats with two adrenals, suggesting that there is an interaction between the effects of unilateral adrenalectomy and adrenal enzyme inhibition. As anticipated, adrenal hypertrophy with increased corticosterone production caused by ACTH infusion resulted in a significant negative relationship between resting and stimulated ACTH levels and adrenal weight. We conclude that when adrenals are enlarged by means that prevent excessive corticosterone secretion, there is a mechanism associated with the increase in adrenal weight that correlates directly with the magnitude of stimulated ACTH secretion. We have reexamined the results of our previous results in the light of these experiments.

Adrenal Glands↗
PubMed1983

Drug-induced adrenal hypertrophy provides evidence for reset in the adrenocortical system.

These studies were performed to determine how bilateral adrenal hypertrophy persists despite normal resting ACTH levels in male rats for weeks after a 3-day course of treatment with cyanoketone (CK). This drug blocks corticosterone synthesis by binding to the enzyme 3 beta-ol-dehydrogenase-delta 5, delta 4-isomerase (EC 1.1.1.51). Although plasma ACTH levels were significantly elevated at all times during the course of treatment with CK, ACTH and corticosterone levels of CK-treated rats were normal thereafter compared to those in control rats killed in the morning. Despite these normal ACTH levels, adrenal weight remained elevated (by 100%) for at least 14 days. We determined that increased ACTH secretion was required to initiate and maintain the adrenal growth response to CK. Rats pretreated with hypophysectomy or dexamethasone (1 mg/kg) did not respond with increases in adrenal weight after CK treatment. Sustained elevations in ACTH during CK treatment were required for increased adrenal weight, because rats treated with dexamethasone 3 h after CK injection did not have enlarged adrenals at 24 h. Increased adrenal weight was not sustained after removal of supranormal levels of ACTH achieved by infusion, suggesting that after adrenal hypertrophy is achieved by ACTH, elevated ACTH levels are also required to maintain adrenal enlargement. Finally, ACTH and corticosterone levels were measured in the evening (at the peak of the diurnal rhythm in the adrenocortical system of rats) in CK-treated rats. Evening ACTH levels were significantly elevated in CK-treated rats compared to those in controls 7, 10, and 14 days after the onset of 3 days of treatment with CK; however, corticosterone levels were normal. The effects of CK on the adrenocortical system were exerted via the adrenal, since adrenalectomy normalized the amplitude of the diurnal rhythm of ACTH in CK-treated rats compared to that in adrenalectomized controls. We conclude 1) that adrenal hypertrophy after CK is maintained by increased ACTH secretion which occurs daily in the evening; and 2) that the results provide evidence for a daily reset of the corticosteroid feedback sensor in the adrenocortical system. This conclusion arises from the findings that there is a normal rhythm in corticosterone levels in CK-treated rats and that morning ACTH levels are normal although evening ACTH levels are significantly elevated.

Adrenal Cortex↗
PubMed1983

Surgery potentiates adrenocortical responses to hypoxia in dogs.

We studied the effect of prior surgery on the ACTH and corticosteroid responses to acute hypoxia. Five conditioned, pentobarbital-anesthetized, gallamine-paralyzed mongrel dogs were exposed to 24 min of isocapnic hypoxia (11% O2/89% N2) 2 hr (Expt I) and approximately 1 week (Expt II) after implantation of femoral arterial and venous catheters. ACTH and corticosteroid responses were assessed by RIA of arterial plasma samples. Arterial PO2 fell similarly in both experiments from 82 to 26 Torr. This caused significant increases in ACTH of similar magnitude in both experiments. Corticosteroid levels increased more in Expt I than Expt II indicating an apparent potentiation by surgery of the adrenocortical response to hypoxia. Two additional dogs were studied in reverse order under lighter anesthesia such that ACTH and corticosteroid levels after surgery were higher than in the first set of experiments. Under these conditions, hypoxia still produced a large increase in ACTH and corticosteroids after acute surgery. Correlation of log ACTH with corticosteroid levels (adrenal dose response) revealed a significant increase in slope in dogs with acute surgery suggesting that surgery interacted with hypoxia either to change the metabolic clearance rate of corticosteroid or to increase adrenal sensitivity to ACTH.

Adrenal Cortex Hormones↗
PubMed1982

Comparison of canine corticosteroid responses to mean and phasic increases in ACTH.

To determine the dynamics and magnitudes of adrenal corticosteroid responses to ACTH, we measured arterial plasma ACTH and corticosteroid concentrations in conscious dogs during infusions of ACTH or saline. Synthetic alpha 1-24-ACTH was infused at rates of 300,900, or 4,500 ng/30 min either as constant infusions or as three equal short infusions at 10-min intervals. In dogs infused with saline, plasma ACTH fluctuated, whereas corticosteroids did not, suggesting that ACTH is secreted episodically in dogs as in man. The magnitudes of the plasma corticosteroid responses to ACTH infusions were linearly related to the logarithm of the total amount of ACTH infused in 30 min and not to the pattern of administration. In all ACTH infusion experiments, the lag between an increase in arterial ACTH and corticosteroids was not less than 3 min. Mean ACTH half-disappearance time, metabolic clearance rate, and volume of distribution estimated from the different experiments ranged between 1.8 and 2.1 min, 24 and 38 ml . kg-1 . min-1, and 95 and 114 ml/kg, respectively. Collectively, these results explain the apparent paradox that corticosteroid responses to ACTH-releasing stimuli can be initiated before a detectable increase in ACTH above the highest control value (Wood et al. Apparent dissociation of ACTH and corticosteroid responses to ml/kg hemorrhage in conscious dogs. Endocrinology In press).

Adrenal Cortex↗
PubMed1982

Pituitary-adrenal function in rats chronically exposed to cold.

Exposure to cold for 2 weeks was used to assess the effects of a sustained stimulus on pituitary-adrenal function in male rats. The diurnal peak in plasma and adrenal corticosterone was advanced by 4 h during the first 24 h of exposure to cold but returned to its usual time (2000 h) by the next day. Plasma ACTH and corticosterone levels were generally greater at all times during the 24-h cycle in animals exposed to cold for up to 2 weeks, with the greatest increase occurring consistently at the time of peak. When rats exposed to cold for 1 week were returned to a normal 24 C environment, plasma corticosterone tended to increase. Plasma ACTH and plasma and adrenal corticosterone responses to a superimposed acute provocative stimulus (ip saline injection) were faster, greater, and more sustained in rats exposed to cold for 3 or 7 days. Similarly, the compensatory adrenal hypertrophy response to unilateral adrenalectomy was greater in cold-exposed rats. Such animals were also more resistant to pituitary-adrenal suppression by prednisolone. In contrast, there was no change in the sensitivity of the adrenal to exogenous ACTH. The results suggest that chronic exposure to cold causes a sustained activation of central mechanisms that regulate pituitary ACTH secretion as well as extra-pituitary mechanisms that regulate adrenal size; it reduces the effectiveness of negative feedback mechanisms, but does not alter those involved in the regulation of adrenal rhythmicity or adrenal sensitivity to ACTH.

Adrenal Glands↗
PubMed1982

Apparent dissociation of adrenocorticotropin and corticosteroid responses to 15 ml/kg hemorrhage in conscious dogs.

The blood pressure, heart rate, ACTH, corticosteroid, vasopressin, and renin responses to rapid 15 ml/kg hemorrhage were measured in six conscious healthy dogs with chronically maintained femoral arterial catheters. The hemorrhage decreased the mean arterial blood pressure slightly (P less than 0.001), increased the heart rate (P less than 0.001), and increased arterial plasma levels of ACTH (P less than 0.01), corticosteroids (P less than 0.001), vasopressin (P less than 0.001), and renin activity (P less than 0.001). Overall and in the individual experiments, there appeared to be little correspondence between the ACTH and corticosteroid responses. In none of the experiments was there a clear rise in ACTH above control levels before the first rise in corticosteroids. To ascertain that adrenal secretion of corticosteroids was increased during 15 ml/kg hypovolemia, changes in the clearance and distribution volume of cortisol were estimated by counting tritium extracted from plasma of five dogs infused with [1,2-3H] cortisol to steady state levels before and during hypovolemia. The stimulus caused a 30% reduction from steady state levels of dichloromethane-extractable tritium counts (P less than 0.001). Combined with the observed increase in plasma corticosteroid levels, these results show that the increase in adrenal secretion of corticosteroids after hemorrhage was underestimated by measurement of changes in peripheral plasma levels. The hypothesis that hemorrhage results in an increase in adrenal sensitivity to ACTH is tested in the following paper.

Adrenal Cortex Hormones↗
PubMed1982

Rapid decreases in adrenal and plasma corticosterone concentrations after drinking are not mediated by changes in plasma adrenocorticotropin concentration.

Rats given water to drink only during a brief daily period respond to water presentation with a rapid decline in plasma corticosterone concentration. To determine whether this response is consequent to a decrease in plasma ACTH concentration or whether it reflects a sudden reduction in adrenal responsiveness to ACTH, we allowed rats access to water for 2 h/day at lights on and measured plasma ACTH and adrenal and plasma corticosterone concentrations at 3- or 5-min intervals after the onset of drinking. Adrenal and plasma corticosterone concentrations decreased significantly within 2-3 min after water presentation in the absence of concomitant changes in plasma ACTH concentration. The effect was apparent by 5 days after initiating the restricted drinking schedule and became stronger with time up to 21 days. Further characterization of the response showed that the in vitro corticosterone secretion of adrenals removed at intervals after water presentation followed the same pattern as the in vivo concentration. When empty water bottles were presented, plasma ACTH and corticosterone concentrations increased. Neither adrenal medullary function nor plasma renin concentration was found to be associated with the decline in adrenal responsiveness to ACTH after drinking. Hemisection of the spinal cord of unilaterally adrenalectomized rats attenuated the corticosterone response regardless of whether the hemisection was contralateral or ipsilateral to the remaining adrenal. These data suggest that the decreases in plasma and adrenal corticosterone concentration occurring after drinking in water-restricted rats are not dependent on changes in plasma ACTH concentrations, but may be related to changes in adrenal blood flow, steroid metabolism and distribution, or neural input to the adrenal cortex.

Adrenal Cortex↗
PubMed1981

Nonsteroidal adrenal feedback demarcates two types of pathways to CRF-ACTH release.

We have tested the relationship between corticosterone (B) and the number of adrenal glands on stimulated corticotropin (ACTH) levels in rats. Rats were supplied throughout the experiment with various doses of B in the drinking fluid beginning 15-20 h before adrenal surgery. Bilateral, unilateral, or sham adrenalectomy was followed on the 3rd day by the stimulus of ether vapor or ether and laparotomy with intestinal traction. Plasma ACTH levels 3 min after the stimuli were decreased by both the dose of B and adrenal number; the adrenal number of adrenals, although prestimulus ACTh and B levels were similar across groups. The decrease in ACTH after ether resulted from an interaction between the dose of B and the however there was no interaction between the inhibitors after laparotomy with intestinal traction. These results show that 1) in addition to B, some aspect of adrenal gland number or mass inhibits the ACTH response to stimuli; and 2) the adrenal number input serves as a marker to distinguish between stimuli to ACTH secretion that are inhibited by B at sites proximal and those that are inhibited by B at sites distal to this input.

Adrenal Glands↗
PubMed1981

Dissociation of adrenal corticosteroid production from ACTH in water-restricted female rats.

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.

Adrenal Glands↗
PubMed1981

Return of pituitary-adrenal function after adrenal enucleation or transplantation: diurnal rhythms and responses to ether.

Adrenocortical diurnal rhythms and responses to ether vapor were studied in rats 1, 3, and 5 weeks after bilateral adrenal enucleation, autotransplantation, or sham transplantation in order to 1) determine whether diurnal rhythms in the plasma corticosterone concentration and adrenal responsiveness to ACTH are dependent on innervation of the adrenals, 2) compare regeneration of function of transplanted and enucleated adrenals, and 3) investigate adrenal mass-related nonsteroidal inhibition of ether-stimulated ACTH secretion. Rats in both enucleate and transplant groups exhibited significant morning-evening differences in adrenal and plasma corticosterone concentrations and significant adrenocortical responses to ether 3 and 5 weeks, but not 1 week, after surgery. The morning-evening differences in corticosterone concentration occurred in the absence of significant morning-evening variation in the plasma ACTH concentration, supporting our previous finding of a diurnal rhythm in adrenal responsiveness to ACTH. The responsiveness rhythm cannot be dependent on adrenal nerves unless transplanted adrenals receive functionally specific reinnervation within 3 weeks. The processes of regeneration of function after enucleation and after transplantation are similar; there were no differences in plasma or adrenal corticosterone values between rats in enucleate and transplant groups at any time or under any condition tested. As regeneration progressed, plasma ACTH responses to ether declined in both enucleate and transplant groups in the absence of changes in plasma corticosterone feedback. These results support our previous finding of adrenal mass-related nonsteroidal suppression of ACTH responses to ether.

Adrenal Cortex↗