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Biomedical subjects

J Shinsako

Publications and source records attributed to J Shinsako.

53 records · Page 3Linked to original sources
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

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↗
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↗
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↗
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

Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion.

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.

11-Hydroxycorticosteroids↗
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

Comparison of absorption of cortisone acetate and hydrocortisone hemisuccinate.

In four patients who required maintenance glucocorticoid therapy after bilateral adrenalectomy for Cushing's disease, we compared the effects of im injection and oral ingestion of cortisone acetate and hydrocortisone hemisuccinate. By the former route of administration, cortisone acetate was not effective in elevating plasma cortisol levels or in suppressing plasma adrenocorticotropin, although hydrocortisone was. When given by mouth, no significant difference was found between the two steroids. Therefore, in the treatment of acute adrenal insufficiency or in the maintenance of patients with chronic adrenal insufficiency and in their preparation for surgery or other stressful situations, we advise against im injection of cortisone acetate. Oral ingestion, however, is appropriate for maintenance.

Absorption↗
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↗
PubMed1976

Compensatory adrenal growth: a neurally mediated reflex.

The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adreanl at 12 h resulted in an enlarged right adrenal at 12h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement at 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.

Adrenal Glands↗
PubMed1975

Corticosteroids and ACTH are not required for compensatory adrenal growth.

We have tested the hypothesis that unilateral adrenalectomy results in decreased glucocorticoid secretion, reflexly elevated ACTH secretion, and consequently, compensatory adrenal growth. Plasma ACTH and corticosterone and right adrenal weight were measured during the first 10 days after left adrenalectomy or sham adrenalectomy in young male rats. There is a decrease in plasma corticosterone after unilateral adrenalectomy compared to sham adrenalectomy that persists for 1 h. ACTH is elevated only at 2 h after unilateral adrenalectomy compared to shamoperated rats. Treatment with dexamethasone, shown to abolish the ACTH and corticosterone responses to laparotomy with intestinal traction, resulted in significantly increased adrenal weight after unilateral adrenalectomy by 6 h (wet or dry weight), and at 24 h. Compensatory adrenal growth also occurs after unilateral adrenalectomy in hypophysectomized rats (wet or dry weight). We conclude the compensatory adrenal growth after unilateral adrenalectomy requires neither a virtual decrease in circulating corticosterone levels nor elevated ACTH levels, and speculate that the phenomenon is neurally mediated.

Adaptation, Physiological↗
PubMed1975

Corticosterone-induced changes in hypothalamic corticotropin-releasing factor (CRF) content after stress.

Central and peripheral humoral responses of the adrenocortical system were measured for 2 h after the application of several stimuli. Two min after the onset of the stresses of sham-adrenalectomy or laparotomy with intestinal traction there was a 4-6 fold increase in hypothalamic CRF content as compared to control content, This is the usual CRF response to stress. In contrast, after adrenalectomy or manipulation of the pedicles of adrenal glands; CRF content at 2 min was only slightly increased above baseline values. This finding suggests that touching the adrenal vascular and nervous supply results in a direct neural input to the hypothalamus that is qualitatively different from most other stimuli. At times later than 2 min after stress, whem plasma corticosterone levels rise in the intact rat, the patterns of CRF and ACTH responses that were observed after adrenalectomy were determined by whether corticosterone replacement therapy was given. Without corticosterone replacement, the CRF and ACTH responses to adrenalectomy resembled those of laparotomy with intestinal traction. When corticosterone was administered 2 and 40 min after adrenalectomy, the CRF and ACTH responses resembled those of sham-adrenalectomy. At 20 min, CRF content was low after laparotomy with intestinal traction or adrenalectomy and high after shan-adrenalectomy or adrenalectomy with corticosterone replacement. Plasma ACTH peaked by 20 min, and remained high for 2 h after the first 2 stimuli, and was significantly decreased from the 20 min peak by 40 min after application of the latter stimuli. CRF content increased to a second peak 80 min after laparotomy with intestinal traction or adrenalectomy. This rise in CRF must represent increased formation of the releasing factor because ACTH levels were elevated and constant for the preceding 60 min. After sham-adrenalectomy or adrenalectomy with corticosterone replacement, CRF content and ACTH are low at 80 min. Measurement of circulating ACTH levels in conjunction with CRF content after these stimuli have yielded sufficient information to assign mechanisms of altered synthesis and secretion to explain the observed changes in CRF content. Corticosterone damps the adrenocortical system response to the stimuli of sham-adrenalectomy or adrenalectomy with corticosterone replacement by two mechanisms. Firstly, it acts to inhibit CRF secretion probably via rate-sensitive feedback. Secondly, it acts to inhibit the second wave of CRF formation that is observed 80 min after stress is applied, probably via the proportional feedback mechanism.

Adrenal Glands↗