Response of the interrenal to adrenocorticotropic hormone after short-term thyroxine treatment of coho salmon (Oncorhynchus kisutch)

The effects of experimentally elevated plasma thyroxine levels on the subsequent response of interrenals of coho salmon (Oncorhynchus kisutch) to adrenocorticotropic hormone (ACTH) in vitro were examined. Animals were treated with thyroxine by immersion (200 micrograms/L) for 3 days, which resulted in physiological elevations in circulating thyroxine. In animals treated before the parr-smolt transformation was completed (early smolts), thyroxine had no effect on plasma cortisol levels but significantly enhanced the sensitivity of the interrenal to ACTH in vitro. In animals treated after the period of smoltification (postsmolts), plasma cortisol levels were significantly higher than those of controls; both experimental and control animals had plasma cortisol levels higher than normally observed at this stage of development. The response of the interrenals of thyroxine-treated postsmolts to ACTH in vitro was significantly lower than that of controls. Results from the experiments using early smolts are in agreement with studies in other vertebrates showing that thyroid hormones are involved in maintaining the normal functioning of corticosteroidogenic tissue and suggest that thyroid hormones may be involved in the activation of the interrenal that occurs during smoltification. The results obtained using postsmolts are more difficult to interpret because of the possibility that these animals were physiologically stressed by the treatment. Increased ACTH release in vivo resulting from stress may have led to a depression of interrenal sensitivity to ACTH in vitro and may have masked a refractoriness of the pituitary-interrenal axis to thyroxine.     

Influence of exposure to moderate altitude on the plasma concentraton of cortisol, aldosterone, renin, testosterone, and gonadotropins

The influence of 11 days at moderate altitude (2,000 m) combined with exercise on plasma concentration of testosterone, FSH (follicle-stimulating hormone), LH (luteinizing hormone), cortisol, aldosterone, and renin activity was studied in ten healthy subjects. Within 48 h of arrival at moderate altitude a significant increase in testosterone was found whereas FSH had decreased significantly and LH showed a tendency to decrease. Cortisol increased significantly at the beginning and reached a maximum at the end of altitude exposure. The plasma aldosterone level rose continuously and on the last day of altitude was significantly elevated. Plasma renin activity showed a tendency to decrease. On return to low land all measured parameters returned to base line values within 2 days. The findings of increases in plasma levels of aldosterone and testosterone (and serum T3 and T4, as reported by others) are in contrast to the previously found decrease of urinary excretion of all these hormones. This appears to be a distinct dissociation of serum levels of adrenal (and thyroid) hormones from their urinary excretion. The observed increase in plasma aldosterone is probably mediated through ACTH and the rise in plasma potassium, since plasma renin activity showed an opposite trend. The rise in plasma testosterone is probably of adrenal origin since plasma gonadotropins declined simultaneously. The increase of plasma levels of glucocorticoids, mineralocorticoids, and androgens after an ascent from 600 m to 2,000 m above sea level is compatible with an ACTH-mediated stimulation of the entire adrenal cortex and/or a diminished elimination of adrenal steroids: The concomitant fall of FSH, LH, and plasma renin would then be a consequence of a direct negative feedback inhibition of these hormones.     

Influence of hypothalamic-pituitary-adrenocortical hormones on reproductive hormones in gray wolves (Canis lupus).

The release of hypothalamic-pituitary-adrenocortical hormones was studied in intact and neutered gray wolves (Canis lupus) to determine how these hormones interact and affect reproductive hormones. Experiments were performed on adult wolves anesthetized with 400 mg ketamine and 50 mg promazine. Intravenous (i.v.) injections with 50 micrograms ovine corticotropin releasing factor (oCRF) significantly increased adrenocorticotropin (ACTH; P < or = 0.01), cortisol (CORT; P < or = 0.004), and progesterone (P < or = 0.036), but not beta-endorphin (P > or = 0.52). Since neutered wolves demonstrated dose-dependent elevations in response to ACTH, it was concluded that the progesterone was secreted from the adrenal gland. Basal luteinizing hormone (LH) concentrations in neutered wolves were similar before and 60 min after i.v. injection of 1, 5, or 25 IU ACTH (P > or = 0.36) or 2.2 mg/kg cortisol (P = 0.42). Neither 25 IU ACTH (P = 0.55) nor 0.22 mg/kg dexamethasone (P = 0.49) altered the LH response to injection of LH releasing hormone in neutered wolves. Chronic administration of 0.22 mg/kg/day dexamethasone for 3 d did not alter baseline LH concentrations (P = 0.75). Injection of 1.0 mg/kg naloxone (NAL), however, increased LH concentrations relative to baseline values in both intact (P = 0.032) and neutered (P = 0.0005) female wolves, but not in intact (P = 0.19) or neutered males (P = 0.07). These results indicated that in gray wolves (1) oCRF stimulated the release of pituitary and adrenal hormones in a fashion similar to that of other mammals; (2) the adrenal cortex was capable of secreting progesterone into the systemic circulation; (3) exogenous glucocorticoids did not alter LH concentrations; and (4) endogenous opioids may modulate LH secretion in female wolves.     

Acute effects of metabolic hormones in swine

Many metabolic hormones (glucagon, hydrocortisone, corticosterone, TSH, thyroxine and triiodothyronine) did not stimulate porcine adipose tissue lipolysis in vitro. Growth hormone and ACTH stimulated lipolysis at high concentrations, in the presence of theophylline. Insulin inhibited lipolysis. Infusion of metabolic hormones with measurement of plasma free fatty acid and glycerol concentrations, purportedly indicative of in vivo lipolysis, indicated that glucagon and somatotropin had no effect, adrenocorticotropin increased and insulin depressed plasma concentrations of the metabolites. Overall, the in vitro predicts the in vivo response. There were exceptions, e.g. adrenocorticotropin moderately increased plasma metabolites but had little effect in vitro.     

Effects of continuous elevated cortisol concentrations during oestrus on concentrations and patterns of progesterone, oestradiol and LH in the sow

This study investigated the effect of continuous elevated cortisol concentrations during standing oestrus on time of ovulation and patterns of progesterone, oestradiol and luteinising hormone (LH) in sows. The elevation of cortisol concentrations was achieved through repeated intravenous injections of synthetic adrenocorticotropic hormone (ACTH) every 2 h for approximately 48 h, from the onset of the second standing oestrus after weaning. Treatment was terminated when ovulation was detected (monitored by transrectal ultrasonography every 4h) or when the sow had received a maximum of 24 injections. The dose of ACTH (2.5 microg/kg) was chosen to mimic the cortisol concentrations seen during mixing of unfamiliar sows. The sows (n=14) were surgically fitted with jugular vein catheters and randomly divided into a control (C group where only NaCl solution were injected) or an ACTH group. Blood samples were collected every 2 h. In parallel with the blood sampling, saliva samples for cortisol analyses were taken from eight sows before onset of treatment and from four of the sows during treatment. There was no difference in time from onset of standing oestrus to ovulation between the two groups. The interval between the peaks of oestradiol and LH to ovulation was prolonged in the ACTH group compared to the C group (p<0.05), with a tendency towards an earlier decline of oestradiol in the ACTH group. Cortisol and progesterone concentrations were significantly elevated during treatment in the ACTH group (p<0.001), with cortisol peak concentrations occurring between 40 and 80 min after each ACTH injection. Cortisol concentrations in saliva and plasma were highly correlated (p<0.001). In conclusion, elevated cortisol concentrations from the onset of standing oestrus increase progesterone concentrations and prolong the interval between oestradiol and LH peaks to ovulation, the latter possible due to an early decline in oestradiol concentrations and a change of the LH peak outline. The effect these hormonal changes have on reproductive performance need to be further investigated. Saliva samples might be a useful and non-invasive method to assess cortisol concentrations in sows.     

Plasma cortisol and corticosterone concentrations in the golden hamster, (Mesocricetus auratus)

Because some recent studies of hamster adrenocortical function have depended on older studies that may have been inadequate or misinterpreted, the present study re-examined plasma corticosterone and cortisol concentrations in hamsters under several conditions to determine which plasma glucocorticoid predominated in this animal. Sensitive radioimmunoassays were used to measure separately the two glucocorticoids in the basal condition, after adrenocorticotropin (ACTH) treatment, after acute stress, and after chronic stress. In the basal condition, corticosterone concentrations were 3-4 times higher than those of cortisol. After stimulation, this difference disappeared, but rarely were any hamster's cortisol levels higher than their corticosterone levels. Both ACTH and acute stress elevated plasma corticosterone and cortisol concentrations, but only plasma cortisol concentrations were elevated following chronic stress. The dissociation between cortisol and corticosterone concentrations after chronic stress suggests that the two glucocorticoid hormones in the hamster may be regulated independently. The data also indicate that both corticosterone and cortisol should be measured when assessing adrenocortical function in the hamster.     

Cortisol-suppressible dexamethasone-nonsuppressible cyclic Cushing's disease with evidence of clinical and biochemical remission with bromocriptine.

We report a rare case of a 57-year-old female patient with Cushing's disease who had clinically and biochemically proven cyclicity. There were periodic increases in plasma ACTH and cortisol and urinary free cortisol and 17-OHCS. Plasma CRH was undetectable and plasma ACTH responded to exogenous CRH when basal plasma cortisol was relatively low. Neither plasma ACTH nor cortisol responded to dexamethasone (oral and intravenous) but plasma ACTH was clearly suppressed by cortisol infusion. With 40 mg/day bromocriptine, the periodic hypercortisolemia disappeared and the patient was maintained on remission. The response of plasma cortisol to dexamethasone suppression test was also normalized.     

Maternal reproductive hormone levels after repeated ACTH application to pregnant gilts

Prenatal stress has been seen as a reason for reproductive failures in pig offspring mostly originated or mediated by changed maternal functions. In pregnant gilts, three experiments (EXP I-III) were conducted to characterize the effects of repeated ACTH on maternal cortisol concentrations (EXP I) and on the secretion of maternal reproductive hormones (LH, progesterone, estrone sulfate; EXP II + III). Exogenous ACTH was given six times every alternate day beginning either on day 49 (EXP I + II) or day 28 (EXP III) of pregnancy. As a result of treatment, elevated cortisol levels were observed for more than 6 h (EXP I). Plasma concentrations of LH were at low basal level (0.1-0.2 ng/ml), but showed a pulsatory release pattern both during first and second trimester of pregnancy. The number of LH pulses/6 h (L.S.M. +/- S.E.) of saline treated controls increased with ongoing pregnancy (1.4 +/- 0.1 versus 2.0 +/- 0.2 in EXP III and EXP II, respectively). After ACTH treatment the number of LH pulses did not differ between the two gestational stages (1.3 +/- 0.2 and 1.4 +/- 0.2 in EXP III and EXP II, respectively). However, differences ( P < 0.05) were obtained comparing the LH pulse number of ACTH and saline treated sows during the second trimester of pregnancy. Moreover, areas under the curve (AUC) of each LH pulse and of all LH values over the baseline were significantly reduced by treatment. The levels of progesterone increased (P < 0.05) for 150-170 min after each ACTH application both in EXP II and EXP III. The concentrations of 17alpha-hydroxy-progesterone revealed likewise a significant elevation after each ACTH injection. Throughout EXP III, estrone sulfate concentrations were found to decrease (from 2.8-16.9 ng/ml on day 28 to 0.02-0.04 ng/ml on day 38) but without differences between ACTH-and saline-treated gilts. Further data of EXP II and EXP III, e.g. number of piglets born alive, confirmed the absence of detrimental treatment effects. Thus, repeated ACTH administration with subsequent release of cortisol is able to influence the release pattern of maternal reproductive hormones. However, these findings demonstrate that stress-related effects are dependent on the stage of pregnancy. The detected changes may affect feto-maternal interactions and, as a result, fetal reproductive development.     

Inter-relationships between pituitary-adrenal hormones and catecholamines during a 6-day Nordic ski race

The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), beta-endorphin (beta EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D0), and before and after each day's racing (D1-D6). The mean daily heart rate (fc) was calculated from fc values recorded every minute during the race. The results showed the following: changes in mean fc [from 147 (SEM 3) to 156 (SEM 3) beats.min-1 according to the day] were not significant during the race. Diurnal variations in ACTH, beta EP and C were no longer apparent after the race: evening levels were higher than their respective D0 values during the race, except on D3 when there was a lack of response to exercise in the three hormones. Unlike ACTH and beta EP, pre- and postexercise C values on D1 and D2 were higher than those on the subsequent days (P less than 0.001). In contrast, there was a progressive accumulation of A and NA in pre- and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and beta EP were found especially on D3 and D6 (P less than 0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of recombinant human erythropoietin on anterior pituitary function in patients on chronic hemodialysis.

In 7 patients with end stage renal failure, anterior pituitary function was tested by simultaneous application of maximally effective doses of the hypothalamic releasing peptides, corticotropin-releasing hormone, growth hormone-releasing hormone, thyrotropin-releasing hormone and gonadotropin-releasing hormone, and compared to 8 normal controls. In addition to the pituitary hormones, plasma cortisol, thyroxine and testosterone concentrations were measured. To test for possible effects of treatment with recombinant human erythropoietin (rhu-EPO), all patients with chronic renal failure were studied again after partial correction of anemia by treatment with erythropoietin. Before initiation of rhu-EPO treatment, plasma concentrations of follicle-stimulating hormone were significantly elevated and the thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone blunted when compared to normal controls. Treatment with rhu-EPO induced a significant increase in plasma ACTH and follicle-stimulating hormone concentrations. All other pituitary functions remained unchanged. Thus, the general improvement in well-being, working capacity and sexual activity cannot be attributed to hormonal changes.     

Adrenal and ovarian sources of progesterone secretion in young female fallow deer, Dama dama

Six young female fallow deer, including 3 that were ovariectomized at 9 months of age, were blood sampled at frequent intervals after i.v. injections of (1) ACTH analogue (tetracosactrin), (2) GnRH analogue (buserelin) and (3) saline solution on separate occasions at 11, 13, 15 and 18 months of age. Relative to prechallenge plasma values, ACTH administration resulted in a 4-10-fold increase in mean plasma progesterone concentrations, but only a 10-45% increase in mean plasma cortisol concentrations, within 40 min for entire and ovariectomized does during the prepubertal periods (11, 13 and 15 months) and for ovariectomized does during the post-pubertal period (18 months). Post-pubertal entire does exhibited high mean basal plasma progesterone concentrations (3-4 ng/ml) indicating a luteal source of secretion, with the ACTH-induced progesterone response being additive to the luteal progesterone but of similar magnitude to responses in the ovariectomized does. There was no significant ACTH challenge effect on mean plasma LH concentrations for entire or ovariectomized does at all ages. GnRH administration had no significant effects on mean plasma concentrations of progesterone and cortisol of entire and ovariectomized does, although there was a small increase in mean plasma progesterone values in post-pubertal does that may have reflected a luteal response to GnRH (via LH). GnRH challenge resulted in marked increases in mean plasma LH concentrations but the response patterns were different for the 2 types of does, being more rapid and of higher magnitude for ovariectomized does.(ABSTRACT TRUNCATED AT 250 WORDS)     

A light- and electron-microscopic study of goldfish corticotrops following lesions of the nucleus praeopticus

The nucleus praeopticus (NPO) of the goldfish hypothalamus stimulates the secretion of adrenocorticotropic hormone (ACTH). Electrothermic lesions of the NPO significantly decreased stress-induced increments in plasma cortisol, but were without effect on plasma cortisol concentrations in undisturbed goldfish. Light microscopy and ultrastructural investigations of the corticotrops of goldfish bearing lesions of the NPO failed to reveal any differences in the status of morphological correlates usually associated with alterations in secretory activity. These observations demonstrate that hormones of the NPO-hypophyseal system stimulate ACTH release, but are not required for ACTH biosynthesis in goldfish corticotrops.     

Influence of ACTH on serum hormone content and its anticonvulsant action towards infantile spasms

Ten patients with infantile spasms were treated with ACTH, which resulted in a suppression of thyroxine through an increase of the serum cortisol level and suppression of pituitary TSH secretion. The thyroxine level in the excellent-response group was suppressed more than that in the other groups. There was a statistically significant difference (t-test, p < 0.01) in the suppression of T₄ between the excellent-response group and the others. Although the high cortisol level was essential for the clinical effectiveness of ACTH therapy and the suppression of the thyroid hormones, the therapeutic correlation with the elevated cortisol level might be weak as compared to that with the suppression of T₄. These findings suggest the possibility that the efficacy of ACTH therapy in infantile spasms may depend in part on the suppression of the thyroid hormone.     

Studies of pituitary-adrenal-testis interaction in sheep. II. The effects of repeated injections of adrenocorticotrophic hormone outside the breeding season

The administration of 0.5 mg of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) twice daily for 5.5 d to four rams outside the breeding season caused marked rises in plasma cortisol without any evidence of adrenal depletion. This treatment also caused marked rises in basal plasma follicle stimulating hormone (FSH) concentrations which remained high even after cessation of treatment. Plasma FSH responses to 5 ug of gonadotrophin releasing hormone (GnRH) were consistently observed and ACTH treatment increased the FSH response to GnRH. In contrast, spontaneous fluctuations in the plasma luteinizing hormone (LH) and testosterone concentrations were abolished by ACTH treatment. The quantity of testosterone released after GnRH (estimated by the maximum values reached and by the area under the response curve) was also suppressed while that of LH was only slightly lower. A comparison of the results of this experiment with those obtained in rams during the breeding season showed that the effects of ACTH on LH and testosterone were more marked during the breeding season. In contrast, the effect of ACTH on FSH is to increase the latter during the nonbreeding season, whereas no effect was observed during the breeding season.     

Baseline,diurnal variations,and stress-induced changes of stress hormones in three captive beluga whales,Delphinapterus leucas

Concentrations of plasma adrenocorticotropic hormone (ACTH), cortisol, and aldosterone were investigated in three adult beluga whales (Delphinapterus leucas), held in a large outdoor public aquarium exhibit. The purpose of this study was to evaluate resting concentrations of these hormones and associated diurnal variations with routine interactions and medical procedures. Resting blood samples were collected voluntarily from the ventral fluke veins at predetermined times of the day to evaluate diurnal changes in analyte concentrations. In addition, hematology and serum chemistry analyses were performed to monitor health status and evaluate changes related to physical exam procedures. Analogous sampling was conducted during out-of-water physical examinations and before and after wading-contact sessions (WCS). Baseline stress hormone concentrations (± SD) were as follows: plasma ACTH (8.41 ± 5.8 pg/mL), serum cortisol (1.80 ± 0.71 g/dL), and serum aldosterone (11.42 ± 5.5 pg/mL). Plasma ACTH and cortisol concentrations were consistently higher in early morning than evening, while aldosterone was higher in the evening. All stress-related hormones were significantly elevated during physical examination. Plasma ACTH concentrations were most increased, 5–10-fold, during physical examination, whereas cortisol and aldosterone showed 2–4-fold elevations. Stress response analytes measured during the WCS did not differ significantly from baseline concentrations.     

The effect of ACTH administration on plasma testosterone, dihydrotestosterone and serum LH concentrations in normal men

Plasma cortisol (F), testosterone (T), dihydrotestosterone (DHT) and serum luteinizing hormone (LH) concentrations were measured in 8 normal young men at 8 AM on two control days. Exogenous adrenocorticotrophin (ACTH) 20 U.S.P. units per m² of body surface area every 12 or 6 hours was administered intramuscularly for 4 days. Twenty-four hours after starting ACTH administration, the plasma T and DHT concentrations were significantly lower than those of the control days on a paired t test. No significant change in serum LH concentration could be demonstrated. Similar results were observed after 48, 72 and 96 hours of ACTH stimulation.     

Corticotropin releasing hormone and gonadotropin secretion in physically active males after acute exercise.

Plasma concentrations of corticotropin releasing hormone (CRH) and the serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, adrenocorticotropic hormone (ACTH) and cortisol were measured in seven physically active males after acute exercise on a treadmill using the Bruce protocol. Measurements were made in the basal pre-exercise state, immediately after exercise, and at 30-min intervals for 3 h after exercise. Serum LH concentrations declined following exercise reaching nadir values between 60 and 180 min after exercise (90 min post exercise in the group). The nadir values in individual volunteers were significantly lower than both the baseline and post-exercise levels. This fall in serum LH concentration appeared to follow a slight but significant elevation of the plasma concentration of CRH which reached peak levels when measured immediately post exercise. Plasma ACTH concentrations paralleled the rise in CRH, but fell to undetectable levels of below 13.8 nmol.l-1 (less than 5 ng.l-1) 60 min after exercise. Plasma cortisol concentrations peaked approximately 30 min after the rise in ACTH, after which they gradually declined to baseline levels. Plasma testosterone concentrations paralleled the concentrations of LH. The data suggest that CRH, on the basis of its previously described gonadotropin-depressant property, may be the hormone involved in the exercise-mediated decline in serum LH. Alternatively, some as yet unidentified factor(s), may be involved in producing the altered concentrations of both LH and CRH.     

Age-related changes in blood concentration of hypothalamic-pituitary-adrenal axis hormones, their central and peripheral regulators in healthy men

We studied concentrations of cortisol, its precursors and active form in human blood and relation to the changes in concentration of central and peripheral hormonal regulators (total 36 parameters) in healthy male volunteers aged 18-72 y.o. The study demonstrated a significant decrease in blood concentrations of unutilazed cortisol precursors (pregnenolone and progesterone) with advanced age accompanied by maintenance of total and free cortisol concentrations. We found age-related decrease in ACTH level that is a known hypophysial stimulant of cortisol and cortisol precursor synthesis in adrenal glands. Cortisol and ACTH levels in study population had different correlation behavior in relation to central and peripheral regulators for hormonal axes. CONCLUSION: cortisol level remains stable with advanced age in males despite the decrease in steroidogenic activity and blood ACTH level. This may be due to the imbalance in the regulation of cortisol and ACTH production by central and peripheral regulators especially by hormones of reproductive and somatotrophic axes.     

The effects of smoking on ACTH and cortisol secretion

The relationship among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarettes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. Our data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism. It is not clear whether nicotine or some other stimulus inherent in smoking is responsible for cortisol secretion without ACTH secretion.     

Marathon run: effects on plasma renin activity, renin substrate, angiotensin converting enzyme, and cortisol

Altogether 33 Finnish amateur runners were studied before and after a non-competitive Marathon run over the classical itinerary in Athens in 1976 (n = 8), 1977 (n = 14) and 1978 (n = 11). Plasma renin activity (PRA) rose 3-fold in all runs, whereas plasma renin substrate (RS) concentration did not change significantly. Serum angiotensin converting enzyme (ACE) activity was not changed. Serum cortisol concentration was increased 2-3 fold. The unchanged plasma RS concentration, in spite of increasing PRA, indicates that plasma RS is kept within normal limits during prolonged strenuous physical exercise. One contributing mechanism may be stimulation of RS biosynthesis by cortisol. Low PRA levels in two old runners, 65 and 83 years old, may indicate a decreased ability to respond with renin release to the stimuli of physical exercise.