Effect of the exposure to chronic-intermittent cold on the thyrotropin and thyroid hormones in the rat

Rats exposed to acute cold (4 degrees C for 2 h), chronic cold (4 degrees C), and chronic-intermittent cold (4 degrees C for 2 h daily) were killed after 1, 2, 3, 4, and 10 days of cold exposure. The control group was maintained at 25 degrees C. In each animal, the plasma concentration of thyrotropine (THS), triiodothyronine (T3), and thyroxine (T4) was determined by radioimmunoassay. At the initial time of exposure, elevations in TSH, T3, and T4 were observed in the rats in each experimental group. However, on the 10th day, in rats exposed to chronic-intermittent cold, TSH, T3, and T4 decreased to values lower than the control values. In animals exposed to acute cold as well as to chronic cold no differences were found, with respect to the controls, in TSH and T4. In rats exposed to acute cold for 10 days, the T3 value was lower than the control value; however, in animals exposed to chronic cold, T3 was same as that in the controls. The results indicate that, in the rat, exposure to chronic-intermittent cold produces an inhibition in the secretion of TSH and thyroid hormones.     

Chronic melatonin treatment and the hypothalamo-pituitary-adrenal axis in the rat: Attenuation of the secretory response to stress and effects on hypothalamic neuropeptide content and release

The pituitary-adrenal secretory response to acute and chronic stress, suppressibility of adrenocortical secretions by exogenous glucocorticoids, and hypothalamic content and in vitro release of the two major peptidergic activators of the hypothalamo-pituitary-adrenal (HPA) axis, corticotropinreleasing hormone (CRH) and arginine-vasopressin (AVP), were examined in rats receiving daily melatonin (MEL) injections coincident with the circadian increment of endogenous pineal and adrenocortical secretory activity. After 7 days of MEL administration, the rats displayed a significant attenuation of the adrenocortical secretory response to acute and chronic stress. Chronic MEL treatment also prevented the decline in adrenocorticotropic hormone (ACTH) release resulting from chronic stress exposure. Hypothalamic CRH content was significantly lower in rats receiving MEL treatment, while AVP remained largely unaltered; however, MEL administration counteracted the chronic stress-induced decrease in hypothalamic AVP content and in vitro release. When exposed to dexamethasone in vitro, hypothalamic explants from MEL-treated rats responded with a stronger suppression of CRH and AVP release than those originating from vehicle-injected animals. These observations indicate that MEL attenuates the adrenocortical response to stress and influences the biosynthesis, release and glucocorticoid responsiveness of hypothalamic ACTH secretagogues.     

Stress- and cold-induced adrenocortical responses in repetitively immobilized or cold-acclimated rats

To evaluate the role of adrenocortical hormones in stress- or cold-induced nonshivering thermogenesis, plasma corticosterone (CS) and deoxycorticosterone (DOCS) were measured with the aid of HPLC under various conditions. Repetitive immobilization stress (3 h/day, for 1 or 4 weeks) elevated the resting level (24 h after the last immobilization) of CS, but not DOCS. Acute stress (immobilization for 30 min) or cold exposure (-5 degrees C for 15 min) caused marked increases of CS and DOCS in both nonstressed naive controls and repetitively stressed rats. Four weeks, but not 1 week, of repetitive immobilization stress potentiated the responsiveness of CS to both acute stress and cold, and that of DOCS to acute stress, but not to cold. Cold acclimation (5 degrees C, 4 weeks) significantly elevated both corticosteroids but did not affect the resting levels (18 h after being transferred to 25 degrees C) or the responsiveness of both CS and DOCS to either acute stress or cold. These results suggest that repetitive immobilization stress, but not cold acclimation, could enhance nonshivering thermogenesis, at least in part, through an improvement in the responsiveness of adrenocortical hormone secretion to acute stress or cold.     

Chronic treatment with corticotropin increases the capacity of rabbit adrenocortical cells to convert pregnenolone into androgens

The present study was conducted to evaluate whether the previously demonstrated enhancement in adrenocortical androgen secretion in rabbits chronically treated with ACTH results, in addition to an increased pregnenolone production, from a more efficient conversion of this precursor of steroidogenesis into androgens. To this end, the adrenocortical cells from 14 control and 14 ACTH-treated rabbits (ACTH 1-24,200 micrograms s.c. daily for 12 days) were incubated either in the presence of different concentration of ACTH or with pregnenolone added in amounts from 0.5 to 250 micrograms. The total steroidogenic potency (maximal response to ACTH) was significantly enhanced for cells from ACTH-treated animals, as was the ACTH-induced production of dehydroepiandrosterone (DHEA), DHEA-sulfate, androstenedione and testosterone. In addition the production of these androgens from given amounts of exogenous pregnenolone was also significantly increased. The maximal capacity of adrenocortical cells to convert pregnenolone into androgens averaged (for ACTH-treated vs control group) 130 +/- 34 vs 43 +/- 10 pmol for DHEA, 138 +/- 43 vs 46 +/- 14 pmol for DHEA-sulfate, 99 +/- 31 vs 10 +/- 2 pmol for androstenedione and 8.0 +/- 2.6 vs 2.4 +/- 0.3 pmol for testosterone (P less than 0.001 for all androgens). The addition of ACTH to adrenocortical cells incubated with pregnenolone did not modify the maximal capacity of conversion of pregnenolone into androgens, which was in both experimental groups similar to that documented in the absence of ACTH. Thus, while an acute stimulatory effect of ACTH on adrenocortical steroidogenesis is devoid of any influence on the activity of the post-pregnenolone pathway of androgen synthesis, the chronic exposure of adrenocortical cells to ACTH lead to increased activity of steroidogenic pathway involved in the conversion of pregnenolone into androgens.     

Morphology and functional responses of isolated inner adrenocortical cells of rats infused with interleukin-beta.

The effects of the prolonged infusion with interleukin-1 beta (IL-1 beta) (20 pM.kg-1.min-1) on the function and morphology of the isolated inner cells of the rat adrenal cortex were investigated. After 3 and 5 days of IL-1 beta infusion, the level of circulating ACTH was below the control level, while the plasma concentration of corticosterone was strikingly elevated. After 5 days of infusion, isolated inner adrenocortical cells showed an enhanced basal and ACTH-stimulated corticosterone secretion, and showed a conspicuous hypertrophy. The acute exposure to IL-1 beta 10(-6) M did not affect the secretory activity of dispersed cell from either control or IL-1 beta-infused rats. These findings indicate that the prolonged exposure to high levels of circulating IL-1 beta, like those occurring during chronic inflammatory diseases, is able to enhance the growth and steroidogenic (glucocorticoid) capacity of the rat inner adrenocortical zones. Moreover, they suggest that the mechanism underlying this adrenocorticotrophic effect of IL-1 beta does not involve either a stimulation of the hypophyseal ACTH release or a direct stimulatory effect of monokine on adrenocortical cells. It is suggested that IL-1 beta may activate an intra-adrenal paracrine regulatory mechanism.     

Effect of calcium on adrenocortical secretion

The authors investigated the effect of calcium on the basal cortisol secretion and on the adrenocortical secretory reserve, the indicator of which is the so-called ACTH stimulation test. They revealed that during acute hypercalcaemia there is a significant increase of the basal cortisol secretion. The adrenocortical secretory reserve is significantly reduced during hypercalcaemia, this being manifested by a smaller rise of cortisolaemia after ACTH. The Synacthen test repeated after a 48-hour interval is fully reproducible under normocalcaemia. The basal values and the response to Synacthen do not differ from the control examination. The stimulatory action of calcium can be explained indirectly via other humoral factors, the production of which is enhanced by calcium but also the function of calcium which acts as the so-called "second messenger" in steroidogenesis. Calcium has, however, probably also a direct corticotropic effect, resembling that of ACTH.     

Acute temperature change modulates the response of ICa to adrenergic stimulation in fish cardiomyocytes

The purpose of this study was to investigate how the endogenous catecholamine adrenaline protects sarcolemmal Ca(2+) flux through the L-type Ca(2+) channel (I(Ca)) during acute exposure to cold in the fish heart. We examined the response of I(Ca) to adrenergic stimulation at three temperatures (7 degrees, 14 degrees, and 21 degrees C) in atrial myocytes isolated from rainbow trout acclimated to 14 degrees C. We found that I(Ca) amplitude varied directly with test temperature and was increased by adrenergic stimulation (AD; 5 nM and 1 microM) at all temperatures. However, I(Ca) was significantly more sensitive to adrenergic stimulation at the coldest test temperature. In fact, at 7 degrees C in the absence of AD, I(Ca) was extremely low. The addition of 1 microM AD increased peak I(Ca) 7.2-fold at 7 degrees C, 2.6-fold at 14 degrees C, and 1.6-fold at 21 degrees C and ameliorated the temperature-dependent difference in Ca(2+) influx across the cell membrane. We suggest that this increased adrenergic sensitivity is a critical compensatory mechanism that allows the rainbow trout heart to maintain contractility during acute exposure to cold temperatures. In particular, the tonic level of adrenergic stimulation provided by circulating plasma catecholamines (i.e., in the nM concentration range) may be crucial for effective excitation-contraction coupling in the cold cardiomyocyte.     

Effects of microwaves on the adrenal cortex

Six-hundred-and-one male Long-Evans rats were used to study the effect of microwaves on adrenocortical secretion. Power density ranged from 0.1 to 55 mW/cm2 (SAR 0.02 to 11 W/kg). The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Serum corticosterone (CS) concentration was used as an index of adrenocortical function. Ten different exposure protocols were used to identify confounding factors influencing the sensitivity of adrenal cortex to microwave exposure. Increases in CS concentration were proportional to power density or colonic temperature and inversely proportional to the baseline CS. Increased CS concentration was never observed without increased colonic temperature and was not persistent 24 h after exposure. Acclimation (reduction in magnitude of response) could be noted after the tenth exposure. Facilitated heat loss attenuated the magnitude of CS increases by limiting the degree of hyperthermia. Ethanol enhanced the hyperthermic response and desensitized the adrenal response to microwave hyperthermia by increased baseline CS. Ether stimulated adrenal secretion irrespective of previous microwave exposure or adrenal stimulation induced by microwaves. Minor inhibition was also noted occasionally as decreased CS concentration at lower intensity (less than 20 mW/cm2) and decreased postexposure urinary CS excretion at 40 mW/cm2. Adrenal stimulation required minimally a 20 mW/cm2 (4 W/kg) or 0.7 degrees C increase in colonic temperature. An SAR lower than 4 W/kg may stimulate adrenal secretion by potentiating the hyperthermic effect if the ambient temperature is well above 24 degrees C.     

Specific regulation of ACTH secretion under the influence of low and high ambient temperature—The role of catecholamines and vasopressin

The response of hypothalamo-pituitary-adrenocortical (HPA) axis to different stressors depends on numerous stimulatory and inhibitory signals gathering from various parts of the brain to the hypothalamic nuclei. The present study was aimed at determining whether catecholamines (CA) and vasopressin (VP) play the role in the specific regulation of adrenocorticotropic hormone (ACTH) secretion under the influence of thermal stressors, cold (+4 °C) and heat (+38 °C), applied acutely for 1 h or repeatedly during 7 and 14 day (1 h daily). The results showed that following acute exposure to those stressors, hypothalamic dopamine (DA), noradrenaline (NA) and adrenaline (ADR) concentrations were significantly decreased as compared to non stressed controls. The prolonged exposure to either of the two stressors left hypothalamic CA concentration unaffected. The amount of pituitary VP significantly increased only under the influence of acute heat stress. Prolonged exposure to both stressors induced significant decrease in the pituitary VP content. Unlike the heat, the cold-caused changes in circulating VP did not follow those in the pituitary. The applied stressors significantly increased the amount of the pituitary V1b receptor (V1bR) mainly present at the surface of corticotrophs, depending on both duration of exposure and nature of stressor. Additionally, both cold and heat specifically induced an increase in blood ACTH. In conclusion, this study's results suggest that the role of VP in the regulation of the ACTH secretion in response to cold and heat depends on the type of stressor, whereas the role of the CA depends on the manner of exposure.     

Differential redistribution of protein kinase C in human aldosteronoma cells and adjacent adrenal cells stimulated with ACTH and angiotensin II

We have examined protein kinase C activity and hormone secretion in aldosteronoma cells derived from adrenocortical glomerulosa cells and in adjacent adrenal cells containing adrenocortical fasciculata-reticularis cells. When aldosteronoma cells were stimulated with ACTH or angiotensin II, protein kinase C activity gradually decreased in cytosol whereas it increased in membrane. Coincident with the changes of protein kinase C activity, there was enhancement of secretion of aldosterone. On the other hand, incubation of adjacent adrenal fasciculata-reticularis cells with ACTH induced cortisol secretion and an increase in cytosolic protein kinase C activity, accompanied by a decrease in the enzyme activity in membrane. Upon stimulation with angiotensin II, adjacent adrenal fasciculata-reticularis cells did not secrete cortisol and no significant changes of protein kinase C activities were observed in either cytosolic or membrane fractions. These results indicate that both ACTH and angiotensin II stimulate aldosterone secretion and cause translocation of protein kinase C from cytosol to membranes in aldosteronoma cells, whereas, in fasciculata-reticularis cells, only ACTH stimulates cortisol secretion and this is associated with translocation of protein kinase C in the opposite direction, viz., from membrane to cytosol.     

Influence of intensity and duration of exposure to various stressors on serum TSH and GH levels in adult male rats

The effect of stressor intensity and duration of exposure to the stimuli on adrenocorticotropin (ACTH), somatotropin (GH) and thyrotropin (TSH) concentration in serum was studied in adult male Sprague-Dawley rats. The stressors used were noise, restraint in plastic tubes and immobilization on wood boards. The greatest ACTH release was found in immobilized rats and the smallest in noise-exposed animals. The inhibition of GH secretion was related to the intensity of ACTH release in that maximal GH inhibition was observed in immobilized rats and minimal in noise-exposed rats. The TSH response was more complex. Noise increased TSH release at all periods observed (10, 30 and 60 min); the stimulation of TSH release caused by restraint was significant at 30 and 60 min and was always of lesser magnitude than that in response to noise. Finally, immobilization significantly increased TSH levels at 10 min and decreased them at 30 and 60 min. These results suggest that, under appropriate conditions, all hormones studied discriminate between different stressor intensities. However, the complexity of the TSH response to stressors indicates that this hormone is not an adequate index of the stress experienced by the animals.     

Suppression of ACTH-induced steroidogenesis by supernatants from LPS-treated peritoneal exudate macrophages

The results from a number of clinical and experimental studies have suggested that during endotoxemia, suppression of adrenocortical steroidogenesis may occur. We have examined the possibility that macrophages are the source of a factor that suppresses adrenocortical steroidogenesis. Resident and peptone-elicited peritoneal exudate macrophages (PEM) from C3HeB/FeJ mice were incubated for 4 hr at 37 degrees C in the presence or absence of T cell hybridoma-derived lymphokine (LK) that contained high concentrations of MAF activity (assessed by induction of nonspecific tumoricidal activity in PEM). The LK was removed by rinsing, and fresh medium was added, followed by Salmonella minnesota R595 LPS (final concentration 10 micrograms/ml). After 18 hr at 37 degrees C the PEM supernatants and control medium from flasks without cells were harvested and stored at -20 degrees C. Explanted rabbit adrenocortical cells in 96-well plates were exposed to 30 microliters of PEM supernatant or control medium and ACTH (10 or 100 mU/ml) in a final volume of 120 microliters for 3 consecutive days. The adrenocortical cell supernatants were harvested each day, followed by replenishment of medium, PEM supernatant, and ACTH. Fluorogenic steroid production in wells that received control medium or supernatants from PEM not treated with LPS was normal (0.22 microgram +/- 0.010 (SD) per 5 X 10(4) cells). However, as much as 75 to 95% suppression of steroidogenesis was observed in wells that received supernatants from PEM treated with LK and LPS, compared to 40% suppression in wells that received supernatant from PEM treated with LPS alone. Continued exposure (over 3 days) of adrenocortical cells to supernatants from LPS-treated PEM resulted in progressively decreasing response to ACTH. Comparable suppressive activity was observed in supernatants from LPS-treated bone marrow-derived macrophages. In further experiments, suppression was observed in wells that were pretreated (22 hr) with the appropriate PEM supernatant, and evidence was obtained that the suppressive activity was not due to carry-over LPS. Finally, results from control experiments demonstrated that suppressive PEM supernatants neither inactivate ACTH nor interfere with the assay of fluorogenic steroids. Thus, these results suggest that during endotoxemia, products from LPS-stimulated macrophages may suppress adrenocortical function.     

Relationship between endogenous cyclic AMP production and steroid hormone secretion in chick adrenal cells

Dispersed chick adrenal cells were incubated with either ACTH, cholera toxin or forskolin. All three agents stimulated cyclic AMP accumulation and secretion of corticosterone and aldosterone by the dispersed cells. The dose-response to ACTH was similar for cyclic AMP and corticosterone but aldosterone secretion appeared to be more sensitive to ACTH stimulation. Concentrations higher than 10(-8) M of ACTH caused suppression of corticosterone output but not of cyclic AMP accumulation or aldosterone secretion. A significant cyclic AMP accumulation occurred within 30 min of exposure to ACTH whereas significant increases in steroid secretion were observed only after 30 min. An early increase (within 30 min) in cyclic AMP accumulation with both cholera toxin and forskolin was not accompanied by any significant stimulation of steroid secretion, which occurred only after 120 min. The results with the avian adrenal cells are consistent with the thesis that steroid production in the adrenocortical cells is stimulated by cyclic AMP-dependent pathways, whereas steroid release may be modulated by others.     

Cold-induced changes in breathing pattern as a strategy to reduce respiratory heat loss

Thermoregulatory benefits of cold-induced changes in breathing pattern and mechanism(s) by which cold induces hypoventilation were investigated using male Holstein calves (1-3 mo old). Effects of ambient temperatures (Ta) between 4 and 18 degrees C on ventilatory parameters and respiratory heat loss (RHL) were determined in four calves. As Ta decreased, respiratory frequency decreased 29%, tidal volume increased 35%, total ventilation and RHL did not change, and the percentage of metabolic rate attributed to RHL decreased 26%. Total ventilation was stimulated by increasing inspired CO2 in six calves (Ta 4-6 degrees C), and a positive relationship existed between respiratory frequency and expired air temperature. Therefore, cold-exposed calves conserve respiratory heat by decreasing expired air temperature and dead space ventilation. Compared with thermoneutral exposure (16-18 degrees C), hypoventilation was induced by airway cold exposure (4-6 degrees C) alone and by exposing the body but not the airways to cold. Blocking nasal thermoreceptors with topical lidocaine during airway cold exposure prevented the ventilatory response but did not lower hypothalamic temperature. Hypothalamic cooling (Ta 16-18 degrees C) did not produce a ventilatory response. Thus, airway temperature but not hypothalamic temperature appears to control ventilation in cold-exposed calves.     

Studies on lipoprotein and adrenal steroidogenesis: II. Utilization of low density lipoprotein- and high density lipoprotein-cholesterol for steroid production in functioning human adrenocortical adenoma cells in culture

We examined the utilization of human low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol for steroid production in primary monolayer culture cells from adenomas of primary aldosteronism and Cushing's syndrome and an adrenal of nodular hyperplasia of Cushing's syndrome. We compared the data obtained with findings in the case of cultured normal human adrenocortical cells. In the presence of 10(-7) M adrenocorticotropin (ACTH), the addition of either LDL or HDL to the culture medium at a cholesterol concentration of 100 micrograms/ml led to a significant increase in the daily secretion rates of cortisol, dehydroepiandrosterone sulfate (DHEA-S) and aldosterone in the adenoma and nodular hyperplasia cells, as in the normal cells. Although LDL greatly increased the secretion of steroid hormones, no significant difference in steroid secretion following the treatments with LDL and HDL were observed in these cultured cells. The contribution of endogenous cholesterol to steroid production was also high, thereby indicating that the neoplastic transformation did not have untoward effects. Cells from adenomas of primary aldosteronism secreted not only aldosterone, but also cortisol and DHEA-S. The daily secretion rates of these steroids were markedly increased when ACTH was added to the medium. With prolonged exposure to ACTH, however, the rate of aldosterone secretion showed a gradual decrease with the incubation time. This decrease might be due to the impaired conversion of corticosterone to 18-hydroxycorticosterone. In case of adenomas in patients with Cushing's syndrome, the secretion of steroid hormones varied in quantity and quality, depending on the type of plasma cortisol response to the rapid ACTH test in vivo, thereby suggesting that the adrenocortical adenoma of Cushing's syndrome might be divided into two subtypes. These results indicate that human functioning adrenocortical adenoma cells utilize plasma lipoproteins as a source of cholesterol for steroidogenesis during the prolonged stimulation of steroid secretion.     

Short ACTH test in assessing hypothalamic-pituitary-adrenocortical function.

The adrenocortical response to the simple 30-minute ACTH stimulation test was compared with the hypothalamic-pituitary-adrenocortical (HPA) response to insulin-induced hypoglycaemia in 25 patients with various degrees of hypothalamic-pituitary malfunction. The correlations between the increase in plasma cortisol during insulin hypoglycaemia and that during ACTH stimulation (r = 0-66) and between peak plasma cortisol levels during the two tests (r = 0-90) were highly significant. Peak plasma cortisol levels in individual patients were similar on both tests, no patient showing any major discrepancy between the two test results. Thus the simple 30-minute ACTH stimulation test seems to be reliable in detecting imparied HPA function.     

Dissociation by cooling of hormone and cholera toxin activation of adenylate cyclase in intact cells.

Cholera toxin, through adenylate cyclase activation reproduced cyclic AMP-mediated effects of thyroid-stimulating hormone (TSH) in dog thyroid slices, i.e. protein iodination, [1-14C]glucose-oxidation and hormone secretion. Iodide and carbamylcholine decreased the cyclic AMP accumulation induced by cholera toxin as well as by TSH, which supports the hypothesis of an action of these agents beyond the steps of hormone-receptor and receptor-adenylate cyclase interaction. Cooling to 20 degrees C did not impair the TSH induced cyclic AMP accumulation in thyroid slices, but completely suppressed the cholera toxin effect. This observation has been extended to other hormones and target tissues, such as the parathyroid hormone (PTH) (kidney cortex), adrenocorticotropic hormone (ACTH) (adrenal cortex) and luteinizing hormone (LH) (ovary systems). As in thyroid, cooling dissociated the cholera toxin and hormonal effects on cyclic AMP accumulation. In homogenate, cooling decreased cyclic AMP generation in the presence of cholera toxin but at 20 degrees C and 16 degrees C a cholera toxin stimulation was still observed. These results bear strongly against the hypothesis that the glycoprotein hormones TSH and LH acetivate adenylate cyclase by a mechanism identical to cholera toxin.     

Effects of heat stress on serum progesterone in cyclic ewes and on progesterone and cortisol response to ACTH in ovariectomized ewes

The daily mean of serum progesterone in cyclic ewes (N = 5) as well as the profile characteristics of progesterone and cortisol in response to an acute single dose (5 i.u./kg liveweight 0.75) of adrenocorticotrophic hormone (ACTH) into ovariectomized ewes (N = 4) was investigated during exposure to a constant thermoneutral temperature of 18 +/- 1 degree C or to a daily cyclic heat stress temperature of 18 degrees C-35 degrees C-18 degrees C, in an environmental chamber. Serum collected daily from the cyclic ewes was assayed for progesterone, while serum collected more frequently for 10 h, on the 14th day of exposure to the respective temperature, from the ovariectomized ewes was assayed for progesterone and cortisol by RIAs. In cyclic ewes, heat stress increased the area under the daily progesterone curve (P less than 0.09) but had no effect on progesterone concentration after the regression of the CL. In ovariectomized ewes, ACTH significantly elevated the response of both cortisol and progesterone (r = 0.75, P less than 0.001) within 10-15 min of injection. In the ovariectomized ewes and during heat stress, the responses of progesterone and cortisol to ACTH were characterized by an initial acute rise, a transient drop, a steep elevation and a gradual but prolonged decline. During thermoneutral temperatures, this biphasic response pattern was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of acute stress, (1-24)ACTH administration and changes in superfusion temperature and flow rate on the in vitro secretion of glucocorticosteroids and aldosterone from the Mongolian gerbil (Meriones unguiculatus) adrenal gland

The release of glucocorticosteroids and aldosterone rapidly decreased after start of superfusion and reached a steady base-line within 60-90 min of superfusion. While secretion markedly varied between experiments, it was very constant in the same experiment (coefficient of variation: 7.4-2.2% for glucocorticosteroids and 5.8-3.9% for aldosterone). After repeated exposure of adrenal tissue to 1 IU/ml (1-24)ACTH, glucocorticosteroid release progressively increased; under the same conditions aldosterone secretion was not changed. Glucocorticosteroid secretion from glands of animals stressed by 1-hr confinement or of animals injected with 6 IU (1-24)ACTH was significantly higher than that of controls over the 60-min superfusion period. Aldosterone secretion was not affected significantly by these pretreatments. After reduction of temperature from 35 to 1 degrees C, steroid release ceased. Elevation of temperature from 12 to 32 degrees C resulted in a linear increase of glucocorticosteroid and aldosterone secretion. A highly significant positive correlation was found between glucocorticosteroid and aldosterone amounts secreted from adrenals superfused at temperatures between 1 and 35 degrees C (r = 0.91, n = 116, P less than 0.0001). Changes of flow rate from 0.5 to 1.5 ml/min for 5 min induced a short term (1 min) stimulation of glucocorticosteroid and aldosterone release; reduction of flow rate to 0.5 ml/min for 5 min drastically diminished secretion of steroids below control levels for 1 min.     

ACTH secretion and ventilation increase at similar arterial PO2 in conscious rats

To compare the arterial PO2 (PaO2) at which adrenocorticotropic hormone (ACTH) secretion and ventilation are stimulated, conscious rats with chronic femoral arterial catheters were exposed for 50 min to 21, 18, 15, 12, or 9% O2. Decreases in arterial PCO2 (PaCO2) and increases in arterial pH and adrenocortical system activity occurred consistently throughout the exposure period in rats exposed to 9 or 12% O2. In contrast, changes in PaCO2 or pH were only transient or delayed, plasma ACTH did not change, and plasma corticosterone only increased after 20 min in rats exposed to 15 or 18% O2 relative to those breathing 21% O2. Omitting the large blood sample at 20 min for ACTH eliminated the increase in corticosterone in the 15% O2 group. Overall, ACTH increased, and PaCO2 decreased, below PaO2 of approximately 60 Torr. We conclude that ACTH secretion increases at a similar PaO2 as hyperventilation-induced decreases in PaCO2 and thus represents a primary physiological response to acute hypoxia; hemodynamic stimuli may also interact with hypoxia to augment adrenocortical system activity.