Lower Plasma Cortisol Levels Research Articles

A Case of Factitious Adrenal Insufficiency after Vascular Graft Surgery Caused by Spurious Immunometric Assays

A 70-year-old man with abdominal aortic aneurysm underwent surgical repair with Hemashield vascular graft. Postoperatively, he was found to have very low plasma cortisol levels, which failed to increase after stimulation with ACTH. A tentative diagnosis of adrenal insufficiency was made despite the lack of its clinical manifestations and a replacement therapy with hydrocortisone was started. He had also elevated plasma levels of TSH, thyroid hormones and estrogen without any clinical manifestations. Such abnormal hormone levels were spontaneously normalized three months after operation, which was later proven to be factitious by different immunometric assays (IMA). Since the vascular graft coated with bovine type I collagen has been reported to induce a transient immune response in some patients after surgery, we speculated that certain antibodies generated against heterologous collagen and/or yet-unknown components derived from the graft may have caused such factitious data; exogenous addition of bovine type I collagen and albumin to patient's serum, however, failed to affect the assay results. Whatever the cause, caution must be paid that some patients with surgical repair using heterologous materials may have such factitious hormone data by IMAs.

Serotonin, but not melatonin, plays a role in shaping dominant–subordinate relationships and aggression in rainbow trout

The aim of this study was to clarify to what extent the effects of elevated dietary L-tryptophan (Trp) on aggressive behavior and stress responsiveness in rainbow trout are mediated by circulating melatonin and central serotonin (5-HT), respectively. Isolated rainbow trout were paired for 1 h a day for 7 days in order to create fish with experience of being dominant and subordinate. Following this week, the fish were tested for aggressive behavior using a resident–intruder test after which they were subjected to one of four treatments: (1) tryptophan, (2) the selective serotonin reuptake inhibitor (SSRI) citalopram, (3) melatonin, and (4) no treatment (controls). After 7 days of treatment, the fish were subjected to a second resident–intruder test. Trp-supplemented feed resulted in a suppression of aggressive behavior in fish with experience of being dominant. Moreover, fish fed Trp-supplemented feed, regardless of social experience, also displayed lower plasma cortisol levels than controls. These effects of elevated dietary Trp were closely mimicked by citalopram treatment, whereas exogenous melatonin had no effect on either aggressive behavior or plasma cortisol. Thus, the effect of elevated dietary Trp on aggressive behavior and stress responses does not appear to be mediated by melatonin even though elevated dietary intake of Trp resulted in an increase in plasma melatonin concentrations.

ACTH, α-MSH, and control of cortisol release: cloning, sequencing, and functional expression of the melanocortin-2 and melanocortin-5 receptor in Cyprinus carpio

Cortisol release from fish head kidney during the acute phase of the stress response is controlled by the adrenocorticotropic hormone (ACTH) from the pituitary pars distalis (PD). Alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin, from the pars intermedia (PI), have been implicated in cortisol release during the chronic phase. The present study addresses the regulation of cortisol release by ACTH and alpha-MSH in common carp (Cyprinus carpio) and includes characterization of their receptors, namely, the melanocortin-2 and melanocortin-5 receptors (MC2R and MC5R). We could not demonstrate corticotropic activity of alpha-MSH, beta-endorphin, and combinations of these. We do show a corticotrope in the PI, but its identity is as yet uncertain. Carp restrained for 1 and 7 days showed elevated plasma cortisol and alpha-MSH levels; cortisol is still elevated but lower at day 7 than day 1 of restraint. Interrenal response capacity is unaffected, as estimated by stimulation with a maximum dose ACTH in a superfusion setup. MC2R and MC5R appear phylogenetically well conserved. MC2R is predominantly expressed in head kidney; a low abundance was found in spleen and kidney. MC5R is expressed in brain, pituitary PD, kidney, and skin. Quantitative PCR analysis of MC2R and MC5R expression in the head kidney of restrained fish reveals MC2R mRNA downregulation after 7 days restraint, in line with lower plasma cortisol levels seen. We discuss regulation of corticosteroid production from a phylogenetic perspective. We propose that increased levels of alpha-MSH exert a positive feedback on hypothalamic corticotropin-releasing hormone release to sustain a mild stress axis activity.

Stress response dampening indexed by cortisol in subjects at risk for alcoholism.

This study examines the stress-response-dampening (SRD) hypothesis of alcoholism from a novel vantage point. Various investigators have demonstrated that persons considered to be at risk for developing alcohol-related problems exhibit attenuation of stress reactions in psychologically challenging experimental sessions after receiving alcohol. These studies have used autonomic nervous system measures for indexing stress responses. In our report we address the question of whether people with a family history of alcoholism exhibit dampening effects of ethanol in the response of a classical stress hormone (i.e., cortisol). Subjects in this report were 46 healthy male and 40 healthy female adult subjects; 36 of the men were sons and 28 of the women were daughters of alcohol-dependent fathers (sons of alcoholics, SOAs; daughters of alcoholics, DOAs); 12 women and 10 men had no family history of any alcohol use disorders (daughters of nonalcoholics, DONAs; sons of nonalcoholics, SONAs). The subjects were part of a large-scale project in which participants received two laboratory sessions with exposure in each to three experimental paradigms involving psychological stress while various psychophysiological and neuroendocrine measures were taken. In one of the sessions alcohol was administered. In the 1-hour period after termination of the stress paradigms, SOAs showed significantly lower plasma cortisol levels on laboratory days with alcohol administration than on days without alcohol administration at two of the three poststress sampling points. DOAs, however, did not exhibit a dampening pattern for cortisol. In the two control groups of SONAs and DONAs, no stress response attenuation effects of alcohol were observed. The results of experimental laboratory work with individuals at risk of alcoholism in the present and other studies add to the validity of SRD models of this disorder. Research strategies that should provide direct evidence for the SRD hypothesis are addressed in the Discussion section.

Effects of iodized feed on stress modulation in steelhead trout, Oncorhynchus mykiss (Walbaum)

In the aquaculture industry, the physiological systems of fish can be chronically stressed by various biological, chemical and physical factors. Chronic stress leads to a decrease in the overall health and growth of the fish, making them more prone to diseases. Dietary iodine has been shown to reduce this stress response in chickens and increase disease resistance in dairy cattle, but the mechanisms by which iodine affects stress resistance and immunocompetency is not completely understood and has not been extensively studied in fish. This study investigated the effects of iodized feed as a nutritional supplement in relation to stress modulation in steelhead trout (Oncorhynchus mykiss). We investigated effects on primary, secondary and tertiary stress responses by measuring plasma levels of cortisol, glucose and thyroid hormones as well as haematocrit percentage and average growth rate in steelhead trout. Iodine-supplemented fish, on average, had lower levels of plasma cortisol and glucose and lower packed cell volumes than fish fed with regular commercial feed (P<0.05). Iodine-supplemented fish also showed higher levels of thyroid hormones and exhibited better growth over the period of the experiment (P<0.05). It was concluded that, used with other husbandry practices, use of iodine-supplemented feed could lead to better host defence, growth and survival in fish raised in the aquaculture industry.

Altered hypothalamic–pituitary–adrenocortical function in rhesus monkeys ( Macaca mulatta) with self-injurious behavior

Individually housed rhesus monkeys sometimes spontaneously develop self-injurious behavior (SIB) in the form of self-directed biting that, on occasion, results in severe tissue damage and mutilation. We previously demonstrated lower levels of plasma cortisol in rhesus monkeys with a history of self-wounding (SW) when compared to non-wounders (NW). Furthermore, cortisol levels were negatively correlated with rates of self-directed biting. The present study was designed to further characterize the relationships between hypothalamic–pituitary–adrenocortical (HPA) activity, self-wounding, and self-directed biting. Basal 24-h urinary free cortisol excretion, the urinary free cortisol response to a low dose of dexamethasone, and the plasma cortisol response to ACTH were examined in 24 individually housed rhesus monkeys, based on wounding history, i.e. the presence/absence of a veterinary record of self-wounding, and current rates of self-directed biting, i.e. the median split of self-directed biting frequency (independent of wounding status). There were no reliable group differences on any of the physiological measures when analyzed by wounding history. However, the plasma cortisol response 30 min post-ACTH stimulation was significantly correlated with wounding recency, such that lower responsivity was associated with more recent wounding episodes. When the results were analyzed on the basis of biting frequency, high frequency biters (HFB) compared to low frequency biters (LFB) showed decreased HPA negative feedback sensitivity to dexamethasone and a trend towards an attenuated plasma cortisol response to ACTH stimulation. These findings suggest that SIB in socially reared monkeys is associated with complex changes in HPA axis function that are related to the expression of the pathology, i.e. self-directed biting, and to the recency of a wounding episode. It remains to be determined whether humans who exhibit SIB show similar alterations in HPA function.

Endocrine mediators of seasonal growth in gilthead sea bream ( Sparus aurata): the growth hormone and somatolactin paradigm

Regulation of somatolactin (SL) and the somatotropic axis was examined year-around at three different stocking times (spring, summer, and autumn) in a Mediterranean fish, the gilthead sea bream ( Sparus aurata). The overall timing of plasma growth hormone (GH) increase was similar among trials (late spring–early summer), but the range of variation year-around was different and followed changes in food intake. Total plasma insulin-like growth factor-I primarily followed changes on growth rates, and a close positive correlation between IGF-I and thermal-unit growth coefficient (TGC) was found irrespective of fish stocking time. Thus, the activation of the somatotropic axis preceded always warm growth spurts, whereas the rise of SL in concurrence with low plasma cortisol levels was found at late autumn. This up-regulation of circulating SL titres preceded the winter inhibition of feeding, and it was more severe in big fish (spring and summer stocking times) than in small fish (autumn stocking time), growing with a relative high efficiency during the cold season despite of a severe hypertriglyceridemia and a high hepatosomatic index. These new insights provide good evidence for a different timing of GH and SL increases, and it is likely that the dominant role of SL in energy homeostasis is to be a mediator of the adaptation to fasting after replenishment of body fat stores, whereas GH and IGF-I are perceived as growth-promoting signals in times of food intake and increasing temperature and day-length.

The ectopic expression of the gastric inhibitory polypeptide receptor is frequent in adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia, but rare in unilateral tumors.

Control of cortisol secretion by the abnormal expression of the gastric inhibitory polypeptide receptor (GIP-R) have been observed in some rare cases of ACTH-independent, food-dependent Cushing's syndrome (FD-ACS) due to adrenal adenoma (AA) or bilateral macronodular hyperplasia (AIMAH). This study was performed to determine the prevalence of GIP-R ectopic expression in ACS and its correlation with fasting cortisol levels. GIP-R expression was studied by RT-PCR in 30 unilateral adrenal tumors [16 AA and 14 adrenocortical cancer (AC)] and 8 AIMAH tissues. Fasting and postprandial cortisol levels were assayed, respectively, at 0800 and 1200 h in AA, AC, and AIMAH, and 1 h after a morning standard meal in 6 AIMAH patients. Similar expression of 2 GIP-R isoforms was observed in 1 of 16 AA, 0 of 14 AC, and 4 of 8 AIMAH as well as in the 4 insulinomas used as positive controls. In vitro study of the GIP-R-expressing AA showed stimulation of cortisol secretion and cAMP production by GIP. The fasting 0800-h plasma cortisol level was above 276 nmol/liter in all patients except 1 AA case and 1 AIMAH case, both of whom expressed GIP-R. In the 3 additional AIMAH cases that expressed the GIP-R, fasting plasma cortisol levels were above 276 nmol/liter. This study demonstrates that ectopic expression of GIP-R is rare in AA and is usually associated with the low fasting plasma cortisol levels that characterize FD-ACS. In contrast, GIP-R expression is frequent in AIMAH and might not always be associated with a low fasting plasma cortisol level. This suggests that maintenance of hypercortisolemia in GIP-R- expressing AIMAH does not always depend solely on GIP-R, and that simultaneous abnormal expression of other membrane receptors might be present. The expression of GIP-R could not be observed during malignant transformation of the adrenal cortex. This study highlighted the major role of cAMP alterations secondary to GIP-R ectopic expression in the pathophysiology of AIMAH and in some rare cases of well differentiated benign adrenocortical tumors.

Selection response of cortisol and lysozyme in rainbow trout and correlation to growth

Progeny groups of rainbow trout ( Oncorhynchus mykiss Walbaum) selected for high or low post-stress levels of plasma cortisol, or similarly for high or low post-stress lysozyme activity, have been tested for their response to the selection. In four of the four stress exposures, individuals from the line selected for high cortisol responsiveness displayed significantly higher levels of post-stress cortisol than individuals of the low responding line. Phenotypic correlations of cortisol response between samplings, irrespective of line, were highly significant. The realised heritability of cortisol was 0.50, which is very similar to the estimated h 2 based on the parental generation. Only in the last two of the four stress experiments did the high lysozyme selected line exhibit significantly higher lysozyme activity than the low lysozyme line. The timing of vaccination may cause this, since the vaccine is known to affect lysozyme activity. Breeding values of parents were based on vaccinated fish only. The phenotypic correlations between samplings of lysozyme response were weaker than for cortisol, though still significant. The realised heritability of lysozyme was 0.32, which is also in agreement with the previously estimated h 2. The phenotypic correlations between cortisol and lysozyme in individual samplings were in cases of significance negative. There is qualified support for better growth performance in the low cortisol responding line as compared to the high responding line. The data are not conclusive as to establishing whether selection for altered post-stress lysozyme activity affects growth. In conclusion, the present data confirm that the progeny inherit stress-related traits identified in the parents; the response to selection for both cortisol and lysozyme is encouraging. The practical implications or gain of selecting for either trait under aquacultural conditions is still being resolved.

Die Nebennierenrindenfunktion sehr unreifer Frühgeborener während der frühen postnatalen Phase

In very premature infants of less than 30 weeks gestational age there is no correlation between the severity of illness and plasma cortisol concentrations. Low plasma cortisol levels were measured during critical illness with severe arterial hypotension requiring catecholamine treatment in the first two weeks of life. Thus, a relative adrenal insufficiency is suspected. The pituitary responds to CRH and the adrenal cortex to ACTH. But it is still questionable, wether the response is sufficient. Preterm infants with an impaired adrenal function in the first weeks of life seem to be at a higher risk for developing bronchopulmonary dysplasia. Steroids are effective in the treatment of arterial hypotension and bronchopulmonary dysplasia. Because of the broad spectrum of severe and long-term adverse effects, the treatment with glucocorticoids is recommended only after carefully balancing its benefits and risks.

Transport stress in Atlantic salmon (Salmo salar L.): anaesthesia and recovery

The effects of metomidate anaesthesia on levels of plasma cortisol, glucose, haematocrit and chloride in Atlantic salmon (1+) (Salmo salar L.), after a 2-h transport and during a 48-h recovery period were investigated. The use of metomidate anaesthesia during transport led to a reduced release of cortisol and significantly lower levels of plasma cortisol after a 48-h recovery period. Plasma glucose did not return to basal level after a 48-h recovery period, indicating that even longer recovery may be needed for the fish to return to a pre-stress state. The results show that metomidate anaesthesia combined with a recovery period lessens the stress burden imposed by hauling and transport.

Postoperative plasma cortisol levels predict long-term outcome in patients with Cushing's disease and determine which patients should be treated with pituitary irradiation after surgery.

Transsphenoidal surgery is the treatment of choice for ACTH-producing pituitary adenoma (Cushing's disease) and pituitary irradiation is widely considered the most appropriate treatment for patients with Cushing's disease for whom transsphenoidal surgery has been unsuccessful. We studied 49 consecutive patients who underwent transsphenoidal surgery for the treatment of Cushing's disease at Tokyo Women's Medical University from 1977-1997 with a mean follow-up duration of 87.6 months (range, 24-253 months). We examined the relationship between postoperative endocrinological data, assessed between 3 and 8 weeks after surgery, and long-term outcome and efficacy of pituitary irradiation after surgery. Long-term remission was defined as the regression of the symptom and signs of Cushing's syndrome, and restoration of normal levels of plasma ACTH, cortisol and urinary free cortisol, together with adequate suppression of morning plasma cortisol levels following the administration of low dose (1 mg) of dexamethasone. Thirty patients had no additional treatment after pituitary surgery. Only 1 of 25 patients (4%) whose postoperative plasma cortisol level was less than 2 microg/dl developed recurrent disease whereas 3 out of 5 patients with postoperative plasma cortisol levels higher than 2 microg/dl relapsed. Postoperative external pituitary radiation was used to treat the remaining 19 patients. Four patients who received radiation therapy had a low or undetectable postoperative plasma cortisol level (<2 microg/dl, 56 nmol/L) and all of these patients developed hypopituitarism whereas 5 patients with subnormal plasma cortisol levels (2.0-10.0 microg/dl) remained in remission. Among 10 patients with persistent disease after surgery, 6 entered remission 6-47 months after irradiation but one of them subsequently relapsed after 108 months. These results suggest that 1) additional therapy should be avoided in patients with a postoperative plasma cortisol less than 2 microg/dl because relapse is very rare and radiotherapy will frequently induce hypopituitarism, 2) patients with a subnormal cortisol level following surgery should be treated with pituitary irradiation, because the relapse rate is reportedly high and radiotherapy is effective in preventing relapse, 3) radiotherapy in patients with persistent disease after surgery is effective only in 50% (5/10) of the patients.

Atlantic salmon, Salmo salar L., and Arctic char, Salvelinus alpinus (L.): comparative correlation between iodine-iodide supplementation, thyroid hormone levels, plasma cortisol levels, and infection intensity with the sea louse Caligus elongatus

The interrelationship between plasma cortisol levels, iodine-iodide nutritional supplementation, plasma thyroid hormone levels (tri- and tetra-iodothyronine, T3 and T4 respectively), and infection intensity with the sea louse Caligus elongatus were investigated in Atlantic salmon, Salmo salar L., and Arctic char, Salvelinus alpinus (L.). Cortisol-implanted Atlantic salmon had significantly higher mean intensities of sea lice than salmon not implanted with cortisol. Untreated Arctic char had significantly higher plasma cortisol levels and sea lice infections than untreated salmon. Cortisol-implanted salmon had lower plasma levels of T3 and T4. Salmon and char treated with iodized feed and iodinated water had higher plasma T3 and T4 levels, higher plasma T3/T4 ratios, and lower plasma cortisol levels than controls. Sea lice infections were significantly reduced on salmon treated with either iodized feed (P &lt; 0.05) or iodinated water (P &lt; 0.05). Char treated with iodized feed also had significantly reduced infections (P &lt; 0.05). In general, iodized feed had a greater effect than iodinated water in reducing sea lice numbers. This study indicates that elevated plasma cortisol levels in salmon and char result in lower plasma levels of thyroid hormone and an increased susceptibility to sea lice infections. It is concluded that providing the fish with sufficient iodine-iodide increases thyroid hormone levels, reduces plasma cortisol levels, and reduces susceptibility to sea lice infections.

Multiple courses of antenatal corticosteroids and outcome of premature neonates

Objectives: We sought to examine outcome for premature neonates after multiple courses of antenatal corticosteroids compared with a single course. Study Design: We performed a post hoc nonrandomized analysis on 710 neonates of 25-32 weeks’ gestation who were born to mothers enrolled in the North American Thyrotropin-Releasing Hormone Trial and who received 1, 2, or ≥3 courses of antenatal corticosteroids. Results: There was no detectable clinical difference in incidence of respiratory distress syndrome, chronic lung disease, and intraventricular hemorrhage related to courses of antenatal corticosteroids, and outcome was similar for infants delivered at 7-13 days compared with those delivered at 1-6 days after receiving antenatal corticosteroids. Compared with those who received a single course, neonates who received ≥2 courses had lower birth weights (–39 g, P = .02), and those receiving ≥3 courses had increased risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.3-5.9; P = .01) and lower levels of plasma cortisol at age 2 hours. Conclusion: In this retrospective analysis multiple courses of antenatal corticosteroids did not improve outcome and were associated with increased mortality, decreased fetal growth, and prolonged adrenal suppression. (Am J Obstet Gynecol 1999;181:709-17.)

The effects of common laboratory and husbandry practices on the stress response of greenback flounder Rhombosolea tapirina (Günther, 1862)

This study examined the stress response of the greenback flounder Rhombosolea tapirina to common laboratory and aquaculture practices. Plasma levels of cortisol in wild fish sampled within 2 min of capture were comparable to plasma cortisol values in other species captured from the wild and sampled immediately. Plasma levels of cortisol were significantly higher in wild fish sampled after capture, confinement and transport. The latency of the plasma cortisol response to stress was approximately 10 min. Cultured greenback flounder, exposed to normal husbandry conditions, had low plasma cortisol levels; however, 3 h of crowding combined with 5 min chasing (simulated grading) resulted in significantly elevated cortisol levels for up to 48 h. Plasma cortisol was significantly higher in fish held at medium and high stocking density than at low density. The plasma cortisol stress response of greenback flounder is similar to that shown by other marine teleosts. Plasma lactate levels in wild fish sampled after capture, confinement and transport, were considerably higher than levels in fish sampled within 3 min of capture, or exposed to 30-min exercise. No significant changes in muscle lactate were observed in response to exercise; however, there were significant increases in plasma lactate, and muscle [H +] and a significant decrease in plasma [H +] following exercise, indicating that muscle and blood physiology of greenback flounder do change in response to exercise. Unlike other flatfish, there was little evidence for in situ glycogenesis within white muscle tissue after exercise and there was some indication that greenback flounder have higher aerobic scope than other flatfish studied to date. This study showed that some routine husbandry practices have the capacity to stress greenback flounder.

Suppression of Cortisol Levels in Subordinate Female Marmosets: Reproductive and Social Contributions

Socially subordinate female common marmosets (Callithrix jacchus) have markedly lower plasma cortisol levels than dominant females. Subordinate females also undergo hypoestrogenemic anovulation, and estrogen can elevate glucocorticoid levels. Therefore, we previously hypothesized that this cortisol difference is mediated by rank-related differences in reproductive hormones, probably estradiol. To test this possibility, we characterized the effects of the ovarian cycle and ovariectomy on plasma cortisol concentrations. Beginning in the early follicular phase, basal blood samples were collected from seven cycling female marmosets daily for 16 days and at 2- to 3-day intervals for another 16 days. Samples were collected identically from seven anovulatory subordinate females and seven long-term ovariectomized females. Cortisol levels changed reliably across the ovarian cycle, with levels in the mid- to late follicular, peri-ovulatory, and early luteal phases higher than those in the remainder of the cycle. Cortisol levels of cycling females were significantly higher than those of subordinates at all parts of the cycle, but were significantly higher than those of ovariectomized females only during the midcycle elevation. Unexpectedly, subordinates had significantly lower cortisol levels than ovariectomized females, as well as higher estradiol and estrone levels and lower progesterone and luteinizing hormone (LH) levels. These results confirm that circulating cortisol concentrations are modulated by reproductive function in female marmosets but also indicate that low cortisol levels in subordinate females cannot be attributed simply to hypoestrogenemia. Instead, other factors, such as direct effects of social subordination or suppression of LH levels, contribute to suppression of cortisol in subordinates.

Effectiveness of a short-term group psychotherapy program on endocrine and immune function in breast cancer patients: An exploratory study

Cancer patients who had been treated for early stage breast cancer and were diagnosed with either positive axillary lymph nodes or distant metastases were randomly assigned to either a 13-week experiential-existential group psychotherapy (EEGP) program or a waiting list control (WLC) condition. Endocrine and immune measures were obtained before and after the intervention period. The findings of this study are that, after the 13 weeks of the experiment, patients in the EEGP group showed lower levels of plasma cortisol and lower levels of prolactin as well as lower percentages of natural killer cells, CD8 cells, and CD4 cells in addition to a lower proliferative response to pokeweed mitogen than patients in the WLC group. Importantly, this was only found in those breast cancer patients presenting relatively high endocrine and immune baseline levels, suggesting that the patients' profile with regard to endocrine and immune function at the start of a program can have an important effect. If replicated on a larger scale, the current results may be relevant for the treatment of breast cancer.

How Safe Is Long-term Prenatal Glucocorticoid Treatment?

GLUCOCORTICOIDS are commonly used in obstetric practice, both for maternal immunosuppression and for shortterm treatment of the fetus, usually to accelerate lung maturation when there is threatened preterm delivery. The immediate benefits of short-term prepartum glucocorticoid therapy in maturing the fetal lung and reducing neonatal mortality are clearly supported by controlled studies. 1,2 Recently, long-term prenatal therapy of fetuses potentially affected with congenital adrenal hyperplasia (CAH) has been advocated, 3,4 but the safety of this experimental therapy has not been established in rigorously controlled trials. See also p 1073. Congenital adrenal hyperplasia is a recessively inherited disease in which a disordered steroidogenic enzyme, usually P450c21 (21-hydroxylase), diverts adrenal steroid synthesis away from cortisol toward androgens. 5 In utero, low fetal plasma cortisol levels stimulate increased corticotropin (ACTH) secretion, which in turn stimulates further adrenal steroidogenesis, resulting in even more androgen synthesis. In an XY male fetus, these adrenal androgens have

Peripheral administration of a corticotropin-releasing factor antagonist increases the vocalizing and locomotor activity of isolated guinea pig pups

Guinea pig pups vocalized more and were more active during a 60-min period of isolation in a novel environment when injected SC with 50 μg of the corticotropin-releasing factor (CRF) antagonist, [ d-Phe]CRF 12−41, than when injected with saline vehicle only. More pups exhibited eye closing and extensive piloerection when injected with saline than when injected with the antagonist. Plasma levels of cortisol following testing were not affected by the injections. These results support the hypothesis that endogenous CRF contributes to the normal decline in vocalizing and locomotor activity that guinea pig pups show with continued isolation. The results also suggest that endogenous CRF plays a role in the eye closing and piloerection of isolated pups. The finding that the dose of the antagonist used altered behavior, yet was not sufficient to lower plasma cortisol levels, supports earlier evidence that the observed effects of CRF are not due to the actions of ACTH or glucocorticoids.

Allergen-induced late-phase airways obstruction in the pig: the role of endogenous cortisol

In developing a novel model for studies of the allergen-induced late-phase airways obstruction, by using the pig, the importance of endogenous cortisol levels was examined by the use of metyrapone, a cortisol-synthesis inhibitor. Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen. One group of pigs was treated with a constant infusion of metyrapone in order to maintain low levels of plasma cortisol. Ascaris suum allergen was nebulized into the lower airways and plasma cortisol and catecholamine levels, total lung resistance and dynamic compliance, blood gases and pH, and blood flow in the bronchial circulation were continuously recorded for 8 h. At the time of allergen challenge, the plasma cortisol levels in sensitized pigs were 455 +/- 37 nM and 40.1 +/- 3.8 nM in non-metyrapone-treated and metyrapone-treated pigs, respectively. No difference was seen between the magnitude of the acute bronchoconstrictor response in the two groups. A late airways obstruction, starting at about 4 h, developed only in pigs with low cortisol levels, whereas a late increase in blood flow in the bronchial circulation was seen in both groups, even if a late airways obstruction was absent. Plasma adrenaline did not seem to influence the late-phase reaction. These results suggest that endogenous cortisol levels, but not adrenaline, modify the late response to allergen in the pig. Furthermore, it is suggested that the pig is a suitable model for studies of allergic reactions in the airways, if metyrapone is used to keep plasma cortisol levels within a normal range.