Responsiveness of the interrenal tissue of Jundiá (Rhamdia quelen) to an in vivo ACTH test following acute exposure to sublethal concentrations of agrichemicals

As in many aquatic environments, pollution is a widespread problem in Southern Brazil. In our previous work, we demonstrated that sublethal contamination with some agrichemicals impairs the capacity of fishes to elevate cortisol levels in response to an additional acute stressor. In earlier experiments, the experimental design did not allow us to conclude where this effect occurs. In the present work, we used the adrenocorticotropic hormone (ACTH) challenge test to help us identify if the impairment occur in the interrenal tissue. For this purpose, five experiments were conducted, each with one specific agrichemical (methyl-parathion, atrazine+simazine, atrazine, tebuconazole, and glyphosate) in sublethal concentrations of 16.6% of the LC(50-96h), as previously determined. Fish were subjected to the ACTH challenge test protocol as follows: group 1, were non-injected and maintained as the specific control group; group 2 received an injection of the vehicle alone (the saline group); and group 3 receive an injection of ACTH. One hour later, blood samples were taken from the caudal plexus, using sterile syringes. In all specific control groups, the injection of ACTH induced a strong rise in plasma cortisol, compared with the fish injected only with the vehicle and the non-injected group. Fish exposed to methyl-parathion and tebuconazole did not elevate cortisol in response to the ACTH injection, with values significantly lower than the control fish. Fish exposed to sublethal concentrations of atrazine+simazine, atrazine, and glyphosate showed a rise in plasma cortisol very similar to the control fish. We conclude that the ACTH challenge test revealed that R. quelen exposed to sublethal concentrations of tebuconazole and methyl-parathion had a reduced ability to elevate plasma cortisol in response to an intraperitoneal (i.p.) injection of exogenous ACTH, indicating that the interrenal tissue is the site of the impairment within the HPI axis. These ACTH challenge tests also revealed that the impairment of the cortisol response verified in fish exposed to atrazine+simazine and glyphosate, as shown in our previous work, seems to be related to steps of cortisol secretion in higher levels within the HPI axis.     

Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 micrograms hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.     

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

We tested the hypothesis that the capuchin monkey adrenal (Cebus apella) gland has oscillatory properties that are independent of adrenocorticotropic hormone (ACTH) by exploring under ACTH suppression by dexamethasone: (i) maintenance of a circadian rhythm of plasma cortisol and (ii) clock time dependency of plasma cortisol response to exogenous ACTH. The capuchin monkey had a clear ACTH and plasma cortisol rhythm. Dexamethasone treatment resulted in low non-rhythmic ACTH levels and decreased cortisol to 1/10 of control values; nevertheless, the circadian rhythm of plasma cortisol persisted. We found that cortisol response to exogenous ACTH was clock time-dependent. The maximal response to ACTH occurred at the acrophase of the cortisol rhythm (0800 h). These results suggest that the capuchin monkey adrenal cortex may possess intrinsic oscillatory properties that participate in the circadian rhythm of adrenal cortisol secretion and in the circadian cortisol response to ACTH.     

Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women.

Oxytocin (OT) administration has been shown to inhibit adrenocorticotropic hormone (ACTH)/cortisol secretion in several experimental conditions. In the present study, the plasma OT responses to suckling in 7 lactating women or to mechanical breast stimulation in 6 normally menstruating women (experimental tests) or to sham stimuli in the same subjects (control tests) were measured and correlated with the simultaneous changes in plasma ACTH/cortisol levels. All women showed similar basal levels of OT, ACTH and cortisol, which remained unmodified after sham stimulation. In contrast, both suckling and breast stimulation produced a significant increase in plasma OT levels and a significant decrease in plasma ACTH concentrations. When OT and ACTH data were considered together, a significant negative correlation was found between the OT increase and the simultaneous ACTH decline. Plasma cortisol levels were lower during suckling or breast stimulation than in control conditions. These data show an inverse relationship between plasma OT and ACTH levels during suckling and breast stimulation in humans, suggesting an inhibitory influence of OT on ACTH/cortisol secretion in a physiological condition.     

ADRENAL FUNCTION IN WILD AND REHABILITATED PACIFIC HARBOR SEALS (PHOCA VITULINA RICHARDII) AND IN SEALS WITH PHOCINE HERPESVIRUS-ASSOCIATED ADRENAL NECROSIS

Adrenal function in harbor seals (Phoca vitulina richardii) was evaluated using adrenocorticotrophic hormone (ACTH) stimulation tests and fecal cortisol levels. The effect of ACTH administration on plasma cortisol and aldosterone levels in five free-living and 14 rehabilitated harbor seal pups was determined using enzyme immunoassay and radioimmunoassay, respectively. In free-living seals, injection of ACTH caused a significant increase in mean plasma cortisol but not of mean aldosterone levels 60 min postinjection. In these seals, mean initial plasma aldosterone was significantly higher than initial levels in rehabilitated seals, while initial cortisol levels were similar. Of the rehabilitated seals, eight died with adrenal cortical necrosis associated with herpesvirus inclusions, while six lived to be released. In the seals that were released, both mean initial cortisol levels and response to ACTH decreased through rehabilitation. In the seals that died, mean initial cortisol and response to ACTH increased through rehabilitation. The differences between initial cortisol levels in seals that lived and those that died were significant at weeks two and four of rehabilitation but not at the week of admission. There was considerable individual variation in initial plasma aldosterone levels and responses to ACTH, although initial aldosterone levels were significantly higher in rehabilitated seals that died than in seals that lived. Seals with adrenal necrosis associated with herpesvirus infection did not have decreased adrenal hormone responses to ACTH. Differences between initial hormone levels and responses to ACTH in different groups of seals may be associated with differing stress levels. Fecal cortisol assays were not a useful method of assessing adrenal function in these seals, as measured levels did not correlate with plasma cortisol levels.     

Responses of plasma adrenocorticotropin and cortisol to intravenous injection of synthetic ovine corticotropin releasing factor in the morning and early evening in normal human subjects

This study was designed to compare the responsiveness of adrenocorticotropin (ACTH) and cortisol secretion to corticotropin-releasing factor (CRF) in the morning and early evening in normal human subjects. Synthetic ovine CRF (1.0 micrograms/kg) or normal saline, was administered as an i.v. bolus injection to six normal males at 900 h and 1700 h. Blood samples were obtained before and 15, 30, 60, 90 and 120 min after CRF or saline injection. Significant increases in plasma ACTH and cortisol levels were observed in all subjects at the both time of testing after CRF injection. The net increments in the areas under the concentration curve (areas in the CRF experiment minus those in the saline control experiment) were not statistically different for both ACTH (mean +/- SEM: 41.0 +/- 10.6 pg/ml h in the morning: 51.1 +/- 8.9 pg/ml h in the evening) and cortisol (mean +/- SEM: 28.5 +/- 5.0 micrograms/dl h in the morning; 36.2 +/- 4.0 micrograms/dl h in the evening). Also no significant difference was observed in net increment, peak level and the ratio of peak level to the basal level of ACTH and cortisol after CRF injection. There were no appreciable changes in plasma concentrations of growth hormone, thyroid-stimulating hormone or prolactin, although slight but statistically significant rises in plasma levels of luteinizing hormone and follicle-stimulating hormone were observed. These results suggest that there is no significant difference in responsiveness of the pituitary-adrenal axis to CRF in the morning (900 h) and early evening (1700 h), and thus the time of day will not necessarily have to be considered when CRF is used between these times in a clinical test to evaluate pituitary ACTH reserve.     

Noninvasive monitoring of fecal cortisol metabolites in the eastern chipmunk (Tamias striatus): validation and comparison of two enzyme immunoassays

Monitoring fecal glucocorticoid metabolites in wild animals, using enzyme immunoassays, enables the study of endocrinological patterns relevant to ecology and evolution. While some researchers use antibodies against the parent hormone (which is typically absent from fecal samples), others advocate the use of antibodies designed to detect glucocorticoid metabolites. We validated two assays to monitor fecal cortisol metabolites in the eastern chipmunk (Tamias striatus). We compared an antibody produced against cortisol and one produced against 5α-pregnane-3β, 11β, 21-triol-20-one using a radiometabolism study and an injection with adrenocorticotropic hormone (ACTH). Most cortisol metabolites were excreted in the urine (～83%). Peak excretion in the feces occurred 8 h after injection. Both assays detected an increase in fecal cortisol metabolite levels after injection of ACTH. Males, but not females, exhibited a circadian variation in metabolite levels. The sexes did not exhibit any difference over the time course and route of excretion or the relative increase in fecal cortisol metabolite levels after ACTH injection. The cortisol assay displayed higher reactivity to ACTH injection relative to baseline than did the metabolite assay. While both antibodies gave comparable results, the cortisol antibody was more sensitive to changes in plasma cortisol levels in eastern chipmunks.     

Adrenocorticotropin- and cortisol- induced changes of integrated corticosteroid and androgen plasma levels in male rabbits

Intravenous injection of 2.5 – 20.0 μg/kg body weight (1–24)ACTH resulted in significantly elevated integrated corticosteroid and androgen plasma levels. After intravenous administration of 150 or 225 μg/ animal cortisol plasma corticosteroid (cortisol) levels were significantly elevated 20 min post injection and returned to basal levels at 40 to 100 min p.I. Plasma androgen levels, on the other hand were not changed at all by this treatment.From our experiments it is concluded that (1–24) ACTH exerts a stimulatory effect on androgen release that is not mediated by cortisol.     

Pituitary and adrenal responses to ovine corticotropin releasing factor and vasopressin injected into young and adult guinea-pigs

Comparison of effects of synthetic ovine corticotropin releasing factor (oCRF), Arginine-Vasopressin (AVP) and the combination of both peptides have been tried in adult and 7-days-old guinea-pigs. On plasmas collected 15 min after interscapulary injection, cortisol, aldosterone and ACTH were measured. The different circulating forms of ACTH were isolated by Sephadex G50 column chromatography, with 1% formic acid and measured by radioimmunoassay. Thus, in the guinea-pig plasma, we detected three immunoreactive forms of ACTH: a "big" molecular form (Mr greater than 20000), an "intermediate" (Mr = 9500) and a "little" ACTH form (Mr = 4500) which was eluted in the same fractions as human 1-39 ACTH. In adult guinea-pigs, CRF increased total ACTH and the "intermediate" form and also plasma cortisol concentrations whereas AVP remained without significant effect excepted a rise in cortisol levels. Injected together, CRF and AVP enhanced plasma concentrations of total ACTH, of the three circulating forms and of cortisol. In 7-days-old guinea-pigs, both CRF and AVP increased plasma concentrations of total, of "intermediate" ACTH and of cortisol and aldosterone whereas the combination of both peptides enhanced dramatically plasma concentration of total ACTH suggesting a magnifying effect of AVP on CRF activity still more efficient in young than in adult guinea-pigs.     

Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man.

Corticotrophic secretion of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and suppressed by glucocorticoids. In vitro and preclinical studies suggest that atrial natriuretic factor (ANF) may be a peptidergic inhibitor of pituitary-adrenocortical activity. The aim of this study was to elucidate a possible role of ANF as a modulator of ACTH release in humans. A bolus injection of 100 micrograms human CRH (hCRH) during a 30 min intravenous infusion of 5 micrograms/min human alpha atrial natriuretic factor (h alpha ANF) was administered at 19:00 to six healthy male volunteers. In comparison to saline, a blunted CRH-stimulated secretion of ACTH (mean maximum plasma level +/- SD 45 min after hCRH: saline 46.2 +/- 14.2 pg/ml, h alpha ANF 34.6 +/- 13.8 pg/ml, p-value = 0.007) and a delayed rise (10 min) in cortisol were detected. The maximum plasma cortisol levels remained nearly unchanged between saline and h alpha ANF administration (mean maximum plasma level +/- SD 60 min after hCRH: saline 182 +/- 26 ng/ml, h alpha ANF 166 +/- 54 ng/ml). No effects of h alpha ANF on basal cortisol levels were observed; in contrast, basal ACTH plasma levels were slightly reduced. Basal blood pressure and heart rate remained unaffected. In the control experiment, infusion of 3 IU AVP in the same experimental paradigm increased basal and stimulated ACTH and cortisol levels significantly in comparison to saline. These observations suggest that intravenously administered haANF inhibits the CRH-stimulated release of ACTH in man.     

Feedback suppression of ACTH secretion by cortisol in dogs: lags after large signals equal those following very small signals

Previously, low stepwise infusions of cortisol in resting adrenalectomized dogs (plateaux less than or equal to 6 micrograms/dL) were shown to reduce ACTH secretion only after 20 min. In the present study, large, steep-sloped cortisol signals were used to try to evoke faster feedback. Adrenalectomized male mongrel dogs were maintained on exogenous steroids until 48 h before the experiment. Of the 23 experiments on 15 dogs (under light pentobarbital anesthesia), 12 were on resting dogs, 7 on dogs stressed by variable insulin infusion (keeping plasma glucose at 18-40 mg/dL), and 4 stressed as above but with 4 h of low cortisol infusion (plasma congruent to 5 micrograms/dL) before applying the feedback signal. After a 50-min control period, a 30-min feedback period was initiated by one of two i.v. cortisol signals: (a) injection of 0.3 mg/kg or (b) infusion of 46 micrograms kg-1 min-1. Both raised plasma cortisol above physiological limits (within 2 and 6 min, respectively). In each experiment, 23 timed venous blood samples were assayed for plasma ACTH and cortisol. ACTH secretion rates were calculated continuously using a validated single-compartment method. Results from both types of cortisol signals were indistinguishable, and were thus pooled. In the unstressed dogs, control-period ACTH secretion of 0.97 +/- 0.12 mU kg-1 min-1 showed no significant decline due to the feedback signal for 20.3 +/- 1.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a long-acting somatostatin analogue on pituitary-adrenocortical secretion in normal human subjects

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 micrograms SMS or placebo at 0830 h and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 micrograms or 63 micrograms) at 0900 h after 100 micrograms SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Salivary and plasma cortisol response to adrenocorticotropin administration in pigs

Two experiments were conducted to determine the responsiveness of salivary and plasma cortisol to acute (i.v.), depot (i.m.) and chronic (repeated i.m.) adrenocorticotropin (ACTH) administration in swine. In Experiment 1, barrows (castrated pigs) were assigned to one of three injection treatments: (1) saline i.m. (SHAM1, n=2); (2) 0.75 IU/kg BW ACTH in saline i.v. (ACUTE, n=2); (3) 2.25 IU/kg BW ACTH in gel i.m. (DEPOT, n=3). Total cortisol concentrations were determined for concurrent saliva and blood samples. Correlations between salivary and plasma cortisol within treatments were: SHAM1, r=0.60; ACUTE, r=0.58; DEPOT, r=0.79. In Experiment 2, barrows were assigned to one of two injection treatments: (1) gel i.m. (SHAM2, n=3); (2) 2.25 IU/kg BW ACTH in gel i.m. (CHRONIC, n=4). The injections occurred every 6 h for a total of eight injections. Concurrent saliva and blood samples were obtained every 3 h for 72 h followed by an increasing sampling interval until day 6. Overall correlations between salivary and plasma cortisol were: SHAM2, r=0.30 and CHRONIC, r=0.61. Experiment 1 found that the relationship between salivary and plasma cortisol was stronger during longer (DEPOT) than shorter (ACUTE) ACTH stimulation. Experiment 2 found a strong relationship between the two measurements during chronic ACTH stimulation, but that relationship weakened after ACTH stimulation ceased.     

Adrenocortical responsiveness to the synthetic ACTH 1-17 analogue given at different circadian stages

The study concerns the adrenocortical glucocorticoid responsiveness to the ACTH 1-17 analogue given at different times of the day, namely near to the zenith and the nadir of the circadian curve of plasma cortisol. Two schedules of administration of the heptadecapeptide have been performed: a pulse i.v. injection of 4 microgram; b. i.m. injection of 100 microgram. Both the doses were given to the same subject in the morning and in the evening of different days. The chrono-sensitivity of the adrenal cortex to ACTH 1.17 analogue is well evident after pulse stimulation by a micro-dose of the heptadecapeptide; in fact the plasma cortisol increase from basal values is significantly higher in evening than in the morning (p less than 0.001). The cortico-stimulatory effect of the higher dose of ACTH 1.17 analogue lasts about 12 h. and then plasma and urinary glucocorticoids take the usual circadian pattern again.     

Effects of adrenocorticotropin stimulation on cortisol dynamics of pregnant gilts and their fetuses: implications for prenatal stress studies

The effect of adrenocorticotropic hormone (ACTH) administration on plasma cortisol concentrations was determined in pregnant gilts and their fetuses. In a first experiment, 100 IU ACTH (Synacthen Depot) was administered intramuscularly to the gilts every second day from Days 49 to 75 of gestation. ACTH injections were carried out at 08:00 h and, thereafter, 10 blood samples were taken within the following 8h via jugular catheters. Blood samples were analysed for plasma cortisol concentrations, and results were compared with values from animals which were treated with physiological saline and untreated animals (blood sampling only). The values for plasma cortisol concentrations increased until 3h after ACTH applications to a mean maximum level of 276.5+/-17.2 nmol/l in the whole 4-week stimulation period. Plasma cortisol levels did not return to pre-treatment values within the 8 h post-injection. No differences in cortisol levels were found between the physiological saline and untreated control, and no habituation of the adrenocortical response to ACTH was found during the 4-week stimulation period. In a second experiment, 100 IU ACTH were administered to pregnant gilts at gestation Day 65. After 3 h, fetuses were recovered under general anaesthesia and blood samples were taken from the umbilical vein, artery, and, after decapitation, from periphery. Application of ACTH to the sows significantly increased their plasma cortisol concentrations (P<0.001), and also increased plasma cortisol concentrations in peripheral blood samples from the fetuses (P=0.09) and in the umbilical vein (P<0.001) and artery (P<0.01), respectively. Plasma ACTH concentrations did not differ in fetuses from ACTH-treated or control sows. The results show that in gilts the adrenocortical response to an exogenous application of Synacthen Depot is consistent over time during mid-gestation. Furthermore, cortisol but not ACTH levels were increased in fetuses from ACTH-treated sows, indicating that maternal cortisol can cross the placenta during mid-gestation. The stimulation of maternal cortisol release through exogenous ACTH with subsequent elevation of fetal cortisol levels is, therefore, a useful approach for studying effects of elevated maternal glucocorticoids in prenatal stress studies in pigs.     

Direct and indirect evidence for polypeptide absorption by the teleost gastrointestinal tract

The ability of the gastrointestinal tract of chinook salmon, Oncorhynchus tshawytscha , to absorb polypeptides in vivo was investigated by reference to the appearance of orally administered adrenocorticotropic hormone (ACTH) within the blood of fish previously treated with dexamethasone (3μg g^−l body weight) in order to suppress endogenous ACTH secretion. Further, since cortisol presence within plasma is dependent upon the availability of ACTH, dexamethasone blockade of endogenous ACTH secretion, in conjunction with subsequent measurements of plasma cortisol levels, provides a means by which biological patency of absorbed exogenous ACTH may be demonstrated. Levels of ACTH and cortisol in plasma of dexamethasone-treated salmon were therefore measured for a period of 360 min immediately following oral intubation of ACTH (15μg g⁻¹ body weight). Peak plasma presence of ACTH-like immunoreactivity (676.6 ± 33.6 pg ml⁻¹ plasma) and cortisol (227.1 ± 29.0 ng ml⁻¹ plasma) were recorded 120 min after ACTH administration. Results from the experimental groups were compared to those of 15 control treatments. Since administration of ACTH to chinook salmon elicited a consistent and significant elevation in not only plasma ACTH but also cortisol presence, it is contended that the salmonid gut expresses an ability to absorb polypeptides of dietary origin. The significance of these findings with respect to the oral administration of biologically active peptides and proteins to fish of importance to aquaculture is discussed.     

Combined administration of human corticotropin-releasing factor and lysine vasopressin induces cortisol escape from dexamethasone suppression in healthy subjects

Inadequate suppression of plasma cortisol after 1-2 mg dexamethasone is frequently observed in depressive patients. To further investigate the pathophysiology underlying cortisol nonsuppression after dexamethasone we compared cortisol and corticotropin (ACTH) response to human corticotropin-releasing factor (h-CRF), lysine vasopressin (LVP), and a concurrent administration of both peptides after pretreatment with 1.5 mg dexamethasone in six male controls. Neither h-CRF nor LVP were able to produce a marked elevation of dexamethasone suppressed plasma cortisol and ACTH. If both peptides were administered in combination, a substantial escape of plasma cortisol from dexamethasone suppression was observed. ACTH responses changed in concordance with those of cortisol indicating that the LVP-CRF interaction takes place at the pituitary level. Our finding is consistent with a multihormonal control of pituitary-adrenal activity and bears several implications for interpretation of dexamethasone suppression test results in depressive illness.     

Human corticotropin-releasing hormone test in normal subjects and patients with hypothalamic, pituitary or adrenocortical disorders

Human corticotropin-releasing hormone (hCRH) test was performed in 57 normal volunteers and 102 patients with hypothalamic, pituitary and adrenocortical diseases. Intravenous bolus injection of synthetic hCRH, 100 micrograms for adults or 1.5 micrograms/kg for children, increased plasma ACTH and cortisol levels in about 90% of normal subjects. In 47 patients with Cushing's disease, plasma ACTH tended to show an exaggerated response to hCRH and peak ACTH was the most frequent abnormal component among the several reaction parameters. Poor responders among normal subjects and patients with Cushing's disease had significantly higher plasma cortisol levels before CRH administration. Patients with hypothalamic hypopituitarism showed exaggerated response, whereas patients with primary pituitary lesion, isolated ACTH deficiency or adrenal Cushing's syndrome showed no ACTH response. These differences in the response of patients suggest the value of the hCRH test in their differential diagnosis.     

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.     

Stimulation of the pituitary adrenocortical system in man by cerulein, a cholecystokinin-8-like peptide

The responses of plasma adrenocorticotropin hormone (ACTH) and cortisol to intravenous injection of cerulein (ceruletide), a decapeptide closely related to cholecystokinin octapeptide, were investigated in healthy men. In response to 16 ng/kg cerulein, plasma ACTH rose from a preinjection level of 42 +/- 11 pg/ml (mean +/- SEM) to a peak level of 81 +/- 16 pg/ml after 15 min. This ACTH increase was followed by a rise in plasma cortisol from a preinjection value of 10.3 +/- 0.9 microgram/dl to a peak value of 17.7 +/- 1.7 microgram/dl after 30 min. This is the first report of the potent stimulating effect of a cholecystokinin-8-related peptide on the pituitary-adrenal system in man.