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M F Dallman

Publications and source records attributed to M F Dallman.

At least 163 records · Page 9Linked to original sources
PubMed1981

Adrenal sensitivity to adrenocorticotropin varies diurnally.

To further characterize diurnal changes in the rhythm in adrenal responsiveness to ACTH, we have measured ACTH distribution volume, MCR, and t 1/2. These do not change between morning and evening in groups of untreated, dexamethasone-pretreated, or hypophysectomized female rats. To characterize the nature of the change in adrenal responsiveness to ACTH, dexamethasone-pretreated rats were infused for 2 h with a variety of doses of ACTH in the morning and evening. The adrenal response to an infusion rate of ACTH that maximally stimulated the adrenals (200 pg/100 g BW.min) was the same in the morning and evening, showing that adrenal capacity does not change. However, infusion of ACTH at lower rates (50-100 pg/100 g BW.min) revealed that the slope of the steroid response curve increased between morning and evening, demonstrating a diurnal change in adrenal sensitivity to ACTH. These results together with previous data showing that the magnitude and time course of the adrenal cAMP response to ACTH changes diurnally strongly suggest that ACTH receptor affinity or coupling with adenylate cyclase changes diurnally. In other experiments, plasma ACTH and corticosterone levels were determined in groups of young and adult male and adult female untreated rats killed at 4-h intervals around the clock. Peak sensitivity to ACTH was found at lights-out, and trough sensitivity was found at lights-on, suggesting that the experimentally demonstrated rhythm occurs normally.

Adrenal Glands↗
PubMed1981

Insulin-induced hypoglycemia in conscious dogs. I. Dose-related pituitary and adrenal responses.

We have measured changes in plasma glucose, ACTH, corticosteroids, and vasopressin and hematocrit after five doses of insulin in six conscious dogs. We found insulin dose-related changes for each of these responses (P less than 0.01, by two-way analysis of variance). The increases in plasma ACTH and hematocrit correlated to the decrease in plasma glucose; the increase in plasma vasopressin was more strongly correlated with the increases in plasma Na+ than with the decreases in plasma glucose. Each dog appeared to have a characteristic ACTH response curve; therefore, the relationship between plasma glucose and plasma ACTH responses varied among dogs, but was significant in five of six dogs studied. Maximal plasma corticosteroid responses occurred with submaximal plasma ACTH responses (200-600 pg/ml). A single dose of insulin produced reproducible changes in plasma ACTH when given to five dogs in three separate experiments over a 2- to 6-month period. In these experiments, the measurement of ACTH allowed us to distinguish three levels of response to insulin, whereas measurement of the corticosteroid response allowed us to distinguish only two levels of response.

11-Hydroxycorticosteroids↗
PubMed1981

Neuroendocrine regulation of stimulated ACTH secretion.

Two models of corticosteroid inhibition of stimulus-induced ACTH secretion are discussed. Modulation of ACTH secretion by a nonsteroidal factor related to adrenal mass is reviewed. Experiments are presented that compare feedback inhibition of ACTH affected by corticosterone and by adrenal mass. Use of two stimuli to ACTH secretion and manipulation of two feedback signals allow the conclusion that only one of the steroid feedback models will satisfy the data, and that corticosteroid feedback inhibition of stimulus-induced ACTH secretion must be exerted at at least two sites in the central nervous system.

Adrenal Cortex Hormones↗
PubMed1980

Compensatory adrenal growth in immature and mature male rats.

We measured adrenal weights 3 days after left- or sham-adrenalectomy in male Sprague-Dawley rats at 10 ages between 10 and 155 days. Compared to sham-operated rats, the magnitude of the increase in right adrenal weight ranged between 19 and 32% after unilateral adrenalectomy and was significant at 10, 20, 40, 50, and 60 days (p less than 0.01). Comparing left with right adrenals in unilaterally adrenalectomized rats, the right was heavier at all ages (p less than 0.01); in animals 40 days and younger, this is due to normal adrenal growth rate (0.3 mg/day) as well as compensatory adrenal growth, while in older animals normal growth rate is slow (0.04 mg/day) and this difference in left and right adrenal weights is due primarily to compensatory growth. We conclude from this study that compensatory adrenal growth occurs 3 days after left adrenalectomy at all ages except 15 and 30 days. Resting levels of plasma ACTH and corticosterone did not differ between left- and sham-adrenalectomized rats at any age. The ACTH response to 1 min exposure to ether vapors was markedly reduced in 7- and 12-day-old rats (p less than 0.01). We conclude that compensatory adrenal growth is a consistent response 3 days after unilateral adrenalectomy that depends neither on the age at which surgery is performed nor on the capacity of the rat to secrete markedly elevated levels of ACTH.

Adrenal Glands↗
PubMed1980

Adrenal regeneration. Time course, effect of hypothalamic hemi-islands and response to unilateral adrenalectomy.

Regeneration of rat adrenals was studied after bilateral enucleation to determine whether there is a neural component mediating this process as there is in compensatory adrenal growth after unilateral adrenalectomy. Regeneration was approximately 50% complete (based on criteria of wet weight and DNA content) by 10 days after enucleation; at this time circulating ACTH levels were twice as high in enucleates as in sham-operated controls, but corticosterone levels were normal. Regeneration was apparently complete at sometime between 3 and 6 weeks and circulating ACTH and corticosterone levels were normal at these times compared to controls. Unilateral adrenal enucleation resulted in compensatory growth of the opposite gland, not regeneration of the enucleated gland. Unilateral hypothalamic hemi-islands made with a Halász knife resulted in bilateral augmentation of adrenal regeneration at 10 days and 6 weeks. From these results we conclude that adrenal regeneration after bilateral enucleation occurs by different afferent and efferent mechanisms than compensatory adrenal growth after unilateral adrenalectomy. Additional studies were performed in rats 3 and 6 weeks after adrenal enucleation to test whether the adrenal medulla participates either in compensatory adrenal growth or in the augmented ACTH response to ether vapors observed in unilaterally adrenalectomized rats. Normal compensatory adrenal growth occurred 3 days after unilateral adrenalectomy in rats bilaterally enucleated 6 weeks earlier. Prior enucleation did not inhibit the increased ACTH response of unilaterally adrenalectomized rats to ether. Therefore, the adrenal medulla does not mediate compensatory adrenal growth or the augmented ACTH response of unilaterally adrenalectomized rats to ACTH-releasing stimuli.

Adrenal Glands↗
PubMed1980

Stimulus-induced corticotropin-releasing factor content and adrenocorticotropin release are augmented after unilateral adrenalectomy, independently of circulating corticosteroid levels.

There is evidence for a neural link between the adrenal and hypothalamus that may mediate increased corticotropin-releasing factor and ACTH secretion within seconds after bilateral adrenalectomy. These studies on young male rats tested the possibility that functional evidence for adrenal afferent nerves might be revealed by the application of ACTH-releasing stimuli after the acute ACTH and corticosteroid responses to unilateral or sham adrenalectomy had subsided. Resting ACTH and corticosterone levels were not different in the two groups 1, 3, or 7-10 days after adrenal surgery. Despite similar initial conditions, the ACTH response to ether or to laparotomy with intestinal traction (but not to ip saline injections) was greater after unilateral adrenalectomy (P less than 0.01) at times when plasma corticosterone levels were not different. Hypothalamic corticotropin-releasing factor-like activity was higher in unilaterally adrenalectomized than in sham-operated rats 2 min after exposure to ether (P less than 0.05). We conclude that these results may represent a functional demonstration of decreased inhibitory neural feedback from the adrenal to the hypothalamus after unilateral adrenalectomy, and discuss the possibility that the absence of neural feedback may contribute to the well known hyperresponsiveness of bilaterally adrenalectomized rats to ACTH-releasing stimuli.

Adrenalectomy↗
PubMed1980

Adrenocorticotropin inhibits compensatory adrenal growth after unilateral adrenalectomy.

To determine the interaction between ACTH and compensatory adrenal growth after unilateral adrenalectomy, we have studied the adrenals of young male rats treated with saline, ACTH, dexamethasone, or hypophysectomy and left or sham adrenalectomy (Adx or Sham). ACTH injected at the time of adrenal surgery inhibited the normal increase in [3H]thymidine incorporation into right adrenal DNA at 12 or 18 h (P < 0.05), but increased the RNA content. ACTH treatment (2, 4, or 8 U twice daily) in Shams caused a dose-dependent increase in adrenal weight and the RNA to DNA ratio at 24 h and, subsequently, a dose-dependent increase in adrenal DNA content at 72 h. ACTH treatment of Adx prevented the increase in adrenal DNA content at 24 h (P < 0.05), while increasing the RNA to DNA ratio (P < 0.05) in a dose-dependent manner. Treatment of rats with dexamethasone decreased adrenal weight and RNA content and attenuated the normal response to Adx. ACTH (1 U) at the time of adrenalectomy or sham operation in hypophysectomized rats abolished the normal difference between right adrenal weights in the two groups at 3 days. Adrenal growth occurred in rats hypophysectomized and adrenalectomized 24 h previously compared to Sham controls. These results show that adrenal growth mediated by ACTH is a different cellular process (hypertrophy) from that growth triggered by unilateral adrenalectomy (hyperplasia). Treatment with a long acting preparation of ACTH causes adrenals in rats from both the Sham and Adx groups to grow, and the process of ACTH-mediated adrenal growth inhibits the rapid proliferative response to unilateral adrenalectomy. A proliferative response may occur by 3 days during treatment with large doses of long acting ACTH. Treatment at adrenalectomy with synthetic alpha ACTH-(1-24) abolished the normal increase in adrenal weight at 20 h.

Adrenal Glands↗
PubMed1979

The effect of hypothalamic hemi-islands on compensatory adrenal growth.

Unilateral hypothalamic disconnections were made with a Halász knife in young male rats to determine the effects of these lesions on adrenal weight, and the response to unilateral adrenalectomy. Rats were unilaterally adrenalectomized or sham-adrenalectomized 5-7 days after the hypothalamic surgery. No lesion affected adrenal weight in sham-adrenalectomized rats. Compensatory adrenal growth 3 days after unilateral adrenalectomy is prevented by a unilateral hypothalamic hemi-island on the side ipsilateral, not contralateral, to the first removed adrenal (P less than 0.01). Portions of the ipsilateral hemi-island were examined to determine which interrupted the compensatory adrenal growth response. The anterior 90 degrees portion enhanced compensatory adrenal growth (P less than 0.01). The posterior 90 degrees portion only partially inhibited compensatory adrenal growth (P less than 0.05), while the posterolateral portion completely inhibited the response (P less than 0.01). Plasma ACTH and corticosterone levels at the time of sacrifice were unaffected by unilateral adrenalectomy, but were slightly elevated by the hypothalamic cuts. These studies provide further evidence that compensatory adrenal growth is mediated neurally.

Adrenal Glands↗
PubMed1979

Daily rhythms in adrenal responsiveness to adrenocorticotropin are determined primarily by the time of feeding in the rat.

These experiments were done to determine: 1) whether feeding-related shifts in daily corticosterone rhythms are dependent upon changes in ACTH rhythms, 2) whether restricted feeding of rats results in abnormally high ACTH and corticosterone levels (i.e. stress), and 3) whether changes in either insulin or glucose levels might be the concomitants of feeding that change adrenal responsiveness to ACTH. Young male rats (80--90 g) on a 12-h light, 12-h dark cycle were allowed access to one of three diets for 2 h/day beginning either at lights off or lights on. The diets contained 3%, 4.5%, or 11% fat. A group of rats had ad libitum access to the food containing 4.5% fat. On day 20 of this regimen, rats were killed at 2- to 4-h intervals during the next 24 h, and plasma ACTH, corticosterone, insulin, and glucose were measured. Adrenal weight and corticosterone content were also determined. In none of these experiments was an ACTH rhythm demonstrable by analysis of variance. Neither ACTH levels nor adrenal and plasma corticosterone levels were higher in animals fed 2 h/day than in rats eating ad libitum. Peak corticosterone levels occurred just before feeding, and the restricted feeding paradigm appeard to sharpen the daily rhythms. However, there was also an effect of the light-dark cycle on corticosterone measures. Dietary fat content was directly related to increases in body weight and mean insulin levels and infersely related to adrenal responsiveness to ACTH. The data show that: 1) the time of feeding determines the timing of the corticosterone rhythm in the absence of a rhythm in ACTH, 2) restricted feeding is not a stress, and 3) neither insulin nor glucose has a substantial influence on adrenal responsiveness to ACTH.

Adrenal Glands↗
PubMed1978

Nycthemeral rhythm in adrenal responsiveness to ACTH.

Adrenal adenosine 3',5'-cyclic monophosphate (cAMP) and corticosterone responses to exogenous ACTH were found to be about 2.5 times greater in the evening (at lights off) than in the morning (at lights on) in rats. The rhythm in adrenal responsiveness to ACTH was found to persist in rats treated with dexamethasone 15 and 3 h before exogenous ACTH (in the presumed absence of a rhythm in endogenous ACTH). Treatment with p-chlorophenylalanine did not affect the daily rise in circulating ACTH levels but did abolish the rhythm in adrenal responsiveness to ACTH. The magnitude of the rhythm in adrenal responsiveness to ACTH is greater than the magnitude of the rhythm in ACTH. Because the rhythms are dissociable, we conclude that in vivo measurements of adrenal corticosteroid levels do not necessarily reflect ACTH levels.

Adrenal Glands↗
PubMed1978

Hormonal response to stress in the squirrel monkey (Saimiri sciureus).

The pituitary-adrenal and gonadal responses following stress were evaluated in the squirrel monkey. Plasma levels of cortisol (CS), ACTH and testosterone (T) were determined during a 4-h period following the combined stress of capture and ether anesthesia. The results indicated that the squirrel monkey manifests higher basal levels of steroids than typically found in other mammals. The endocrine response following stress was biphasic, involving an initial elevation and subsequent decline in hormone levels. Males manifested significantly higher plasma levels of CS and T and lower plasma levels of ACTH than did females.

Adrenal Glands↗
PubMed1977

Circadian patterns of stress-induced ACTH secretion are modified by corticosterone responses.

To test whether there is a circadian rhythm in the ACTH response to stress, young female rats were exposed to a variety of ACTH-releasing stimuli at 0600 and 1800 h and changes in circulating ACTH and corticosterone were measured. The results of these experiments suggested that after the high intensity stimuli of laparotomy with intestinal traction or 250 mug histamine ip/100 g BW, the morning ACTH response was greater than the evening response. However, the ACTH response to ip saline was greater in the evening in one experiment and greater in the morning in a second experiment. Plasma corticosterone responses were faster and greater in the morning in the first experiment and in the evening in the second experiment. The ACTH response to 125 mug histamine ip/100 g BW was greater in the evening and the change in corticosterone was greater in the morning. Thus, after low intensity stimuli, the ACTH responses appeared to depend on both the lag time prior to the corticosterone response, and its magnitude. To test this possibility, rats were adrenalectomized and the ACTH response was measured 7.5 and 15 min after the start of surgery and after injection with either 2% EtOH-saline, or 50 mug corticosterone at operation, or with 30 mug corticosterone at 5 min. Compared with ACTH levels in rats treated with vehicle, ACTH levels were decreased 7.5 min after 50 mug corticosterone at operation (P less than 0.01), but not after 30 mug corticosterone at 5 min. ACTH levels were slightly reduced 10 min after 30 mug corticosterone at 5 min compared with those of rats injected with vehicle at operation (P less than 0.05). These results are consistent with the interpretation that corticosterone secretion modifies stress-induced ACTH secretion via the fast-feedback effect. Comparison of the ACTH responses to acute adrenalectomy plus injection with EtOH-saline at 0600 and 1800 h demonstrated that, in the absence of a corticosterone response to the stress, the ACTH response is greater in the morning that in the evening (P less than 0.01). Finally, this group of experiments suggests strongly that the responsivenss of rat adrenal glands to ACTH increases markedly between 0600 and 1800 h.

Adrenalectomy↗