Effects of restricting uteroplacental blood flow on concentrations of corticotrophin-releasing hormone, adrenocorticotrophin, cortisol, and prostaglandin E2 in the sheep fetus during late pregnancy.

We have examined the effects of reduced uterine blood flow and prolonged fetal hypoxemia on the temporal relationship between changes in hormones associated with the activity of the pituitary-adrenal axis (corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), cortisol, and prostaglandin E2 (PGE2) in the ovine fetus at 120-125 days of pregnancy, and we sought evidence for placental secretion of CRH and ACTH during prolonged hypoxemia. Uterine blood flow was reduced by placing an adjustable Teflon clamp around the maternal common internal iliac artery to decrease fetal arterial oxygen saturation from mean values of 59.1 +/- 3.3 to 25.7 +/- 4.6% (+/- SEM, n = 10). There was a transient peak in immunoreactive (IR-) CRH at 1-2 h after reducing uterine blood flow. IR-ACTH rose to peak values at +2 h, then gradually decreased to control level by +12 h. Fetal plasma cortisol and PGE2 concentrations were elevated significantly by +2 and +4 h, respectively, and at 20-24 h. The identity of IR-CRH in fetal plasma and in ovine placental extracts was confirmed by HPLC, but there was no consistent umbilical vein--femoral arterial concentration difference for either IR-CRH or IR-ACTH during normoxemia or hypoxemia. We conclude that a sequence of endocrine changes involving CRH, ACTH, PGE2, and cortisol occurs in the fetus during a prolonged reduction in uterine blood flow. However, we did not obtain evidence, for placental secretion of either CRH or ACTH in response to this manipulation.     

Insulin hypoglycemia test and releasing hormone (corticotropin-releasing hormone and growth hormone-releasing hormone) stimulation in patients with pituitary failure of different origin

To investigate the efficacy of endocrine evaluation in diagnosing and localizing the cause of anterior pituitary failure, 17 patients with suprasellar space-occupying lesions, 4 patients with intrasellar tumors, 8 patients with no detectable anatomical lesion, 1 patient with posttraumatic failure and 1 patient with septooptical dysplasia were investigated. Endocrine evaluation consisted of measuring adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) levels during insulin hypoglycemia test (IHT) and after administration of corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH). In addition, basal prolactin levels, gonadal and thyroid function were evaluated. The results showed that 4 of 17 patients with suprasellar tumors had normal ACTH and GH responses during IHT and after releasing hormone (RH) administration. Five of these patients had a normal ACTH or cortisol rise but no GH response during IHT. All 5 had a normal ACTH and 3 had normal GH rise after RH. Seven patients with suprasellar tumors had no ACTH or GH response during IHT, but all had an ACTH response to CRH. Only 3 of this group had a GH response to GRH. There was one exception of a patient who showed a GH and ACTH rise during IHT but only a blunted ACTH and no GH rise after RH administration. Four patients with pituitary failure and no demonstrable lesion had an ACTH rise after CRH but no GH rise after GRH, whereas in 3 patients with isolated ACTH deficiency no ACTH rise after CRH was seen. In 4 patients with nonsecreting pituitary tumors normal ACTH responses to IHT and CRH were seen, whereas GH rose during IHT only in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of corticotropin-releasing hormone on ACTH, cortisol and 13,14-dihydro-15-keto prostaglandin E2 in patients with diabetes insipidus before and after captopril treatment

A corticotropin-releasing hormone (CRH) test was performed on 7 patients with central diabetes insipidus (DI) and on 7 healthy subjects. The test was repeated on the patients with DI after 3 days of oral treatment with captopril at a dose of 100 mg daily. No significant difference in the responses of plasma ACTH and cortisol to CRH between the patients and the controls was found. The short-term captopril treatment resulted in a significant decrease of both basal and CRH-stimulated ACTH and cortisol levels in the patients with DI. CRH did not induce any changes in the stable metabolite of prostaglandin E₂ 13,14-dihydro-15-keto-prostaglandin E₂ (PGE₂-M) in the patients with DI before or after the captopril treatment. The results obtained suggest that vasopressin is not an obligatory factor for a normal ACTH response to CRH. Angiotensin II (A II) is involved in the regulation of ACTH. This study confirmed our previous data showing the lack of any specific effect of CRH on PGE₂ production.     

The use of the corticotropin-releasing hormone test to monitor the recovery of patients with Cushing's disease or Cushing's syndrome due to an adrenal adenoma after adenomectomy

Six patients with Cushing's disease and three with Cushing's syndrome due to an adrenal adenoma were monitored after their adenomectomy with the corticotropin-releasing hormone test to evaluate the progress of recovery of their pituitary adrenal function. Before surgery the patients with Cushing's disease showed either high, normal or low responses of plasma ACTH and cortisol to 100 micrograms synthetic ovine corticotropin-releasing hormone (CRH) administered intravenously, whereas all three patients with Cushing's syndrome due to an adrenal adenoma showed no response of plasma ACTH or cortisol to CRH. One or two months after surgery, the patients who had Cushing's disease had low levels of basal plasma ACTH and cortisol and their responses to CRH were extremely low. However, the same patients were tested later, it was found that their responses to CRH gradually increased and reached normal ranges approximately within one year after tumor removal, which coincided with the overall improvement in their clinical signs and symptoms due to adrenal insufficiency. In contrast, the recovery of the pituitary adrenal function in patients who had Cushing's syndrome due to an adrenal adenoma was not complete even one year after surgery. Thus the corticotropin-releasing factor test is a useful criteria to evaluate the recovery of the pituitary adrenal function in these patients after surgery, since the responses of plasma ACTH and cortisol to the administered CRH are parallel with the improvements in clinical signs and symptoms due to adrenal insufficiency in patients with Cushing's disease.     

Effects of cortisol treatment on brain and adrenal corticotropin-releasing hormone (CRH) content and other parameters regulated by CRH

Corticotropin-releasing hormone (CRH) has been found in both hypothalamic and extrahypothalamic sites of the brain and also in the adrenal medulla. To study the timing and location of delayed glucocorticoid action in rats, we measured the effects of 2-day and 7-day cortisol treatment on immunoreactive CRH concentrations in hypothalamus, cerebral cortex, hippocampus, cerebellum, and adrenal gland. The activity of the hypothalamo-pituitary-adrenal (HPA) axis and the sympathoadrenal system were also measured. Studies were carried out both in the afternoon and/or in the morning, to get information about possible circadian changes. CRH contents were not changed in any brain areas studied, except there was a trend of decrease in the hypothalamus compared to vehicle in the afternoon due to the lack of circadian increase after 7-day cortisol treatment. Pituitary ACTH content decreased significantly after 7-day treatment, while beta-endorphin did not. Plasma levels of ACTH, corticosterone, norepinephrine and epinephrine and adrenal ACTH and beta-endorphin contents decreased after 2-day, adrenal CRH content after 7-day treatment with cortisol. Our findings suggest, that chronic cortisol treatment inhibits the circadian activation of the HPA axis at all levels but has variable effects on baseline measures because it causes different changes in release and synthesis at different sites.     

Adrenocorticotrophin responses to hypoxaemia in fetal sheep are sustained in the presence of naloxone.

We have examined the effects of fetal hypoxaemia, produced by reducing the percent oxygen in maternal inspired air, on fetal plasma concentrations of corticotrophin releasing hormone (CRH), adrenocorticotrophin (ACTH) and cortisol and determined the effects of an opioid receptor antagonist, naloxone on these responses. Hypoxaemia (fetal PO2, 15-18 mmHg) for 60 min provoked a significant (P < 0.05) increase in fetal plasma ACTH and cortisol concentrations at days 125-130 of pregnancy, but did not affect circulating CRH. There was no effect of naloxone administered either intravenously (1.25 mg bolus followed by a 2.5 mg/h continuous infusion for one hour; fetal body weight approximately 2.5 Kg) or via the lateral cerebral ventricle (50 micrograms bolus followed by a 100 micrograms/h infusion for one hour) on this pattern of ACTH and cortisol change nor on the lack of CRH response to hypoxaemia. We conclude that the increase in fetal ACTH and cortisol in response to acute hypoxaemia is not accompanied by an increase in systemic CRH concentrations, nor is the response dependent on short-term opioid regulation.     

Cerebrospinal fluid and plasma corticotropin-releasing hormone in senile dementia.

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, and plasma levels of CRH, ACTH and cortisol were determined in samples taken simultaneously from 28 patients with dementia including senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID), dementia following a cerebrovascular accident (CVD), and the borderline-to-normal state. CRH levels in CSF were significantly reduced in patients with SDAT and CVD, but not in those with MID, as compared with the borderline cases. ACTH levels in CSF were significantly reduced in the patients with SDAT compared to those with MID. Reduced CRH levels in CSF were found in the patients who showed severe dementia and poor activities of daily living (ADL). Plasma levels of CRH, ACTH and cortisol were normal and were not significantly different among the four groups of patients. CRH levels in CSF were positively correlated with ACTH levels in CSF, but not with the levels of plasma CRH, ACTH or cortisol. Plasma CRH levels were positively correlated with plasma ACTH levels. These results suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) CSF CRH is correlated with the severity of dementia and ADL; 3) the levels of CRH in CSF and plasma are independent, and 4) the plasma CRH reflects, at least in part, the activity of the hypothalamic CRH regulating the secretion of pituitary ACTH.     

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.     

Effect of ACTH and CRH on Plasma Levels of Cortisol and Prostaglandin F<Subscript>2α</Subscript> Metabolite in Cycling Gilts and Castrated Boars

The present study was designed to evaluate the effects of synthetic ACTH (1–24, tetracosactid) and porcine CRH on the plasma levels of cortisol and PGF_2α metabolite in cycling gilts (n = 3) and castrated boars (n = 3). The experiments were designed as crossover studies for each gender separately. Each animal received, during three consecutive days; 1) ACTH (Synacthen^® Depot) at a dose of 10 μg/kg body weight in 5 ml physiological saline, 2) porcine CRH at a dose 0.6 μg/kg body weight in 5 ml physiological saline or 3) physiological saline (5 ml). The test substances were administered via an indwelling jugular cannula in randomized order according to a Latin square. The administration of ACTH to cycling gilts resulted in concomitant elevations of cortisol and PGF_2α metabolite with peak levels reached at 70.0 ± 10.0 and 33.3 ± 6.7 min, respectively. Similarly, the administration of ACTH to castrated boars resulted in concomitant elevation of cortisol and PGF_2α metabolite with peak levels reached at 60.0 ± 0.0 and 20.0 ± 0.0 min, respectively. Cortisol peaked at 20 min after administration of CRH in both cycling gilts and castrated boars with maximum levels of 149.3 ± 16.5 nmol/1 and 138.3 ± 10.1 nmol/1, respectively. It can be concluded that administration of synthetic ACTH (tetracosactid) to pigs caused a concomitant elevation of cortisol and PGF_2α metabolite levels in both cycling gilts as well as castrated boars. The administration of CRH to pigs resulted in an elevation of cortisol levels in both cycling gilts and castrated boars. Conversely, PGF_2α metabolite levels were not influenced by the administration of CRH either in cycling gilts or in castrated boars.     

Functional characteristics of the bovine hypothalamic-pituitary-adrenal axis vary with temperament

Hypothalamic-pituitary-adrenal (HPA) axis function, in Brahman heifers of differing temperament, was evaluated using separate challenges with CRH and ACTH. Exit velocity (EV) measurement was used to classify heifer temperament as calm [C; consisted of 6 slowest heifers (EV=1.05+/-0.05 m/s)] or temperamental [T; 6 fastest heifers (EV=3.14+/-0.22 m/s)]. During the 6 h prior to CRH challenge, areas under the ACTH (P=0.025) and cortisol (P<0.001) curves were greater in the temperamental heifers. Baseline cortisol (P<0.001) but not ACTH (P=0.10) differed between temperament groups. Following CRH challenge, areas under the ACTH (P=0.057) and cortisol (P<0.01) response curves were greater in the calm animals. The same animals were subjected to an ACTH challenge 14 d following their utilization in the CRH stimulation experiment. Prior to ACTH challenge, baseline cortisol concentrations were higher (P<0.001) in the temperamental heifers (T=18+/-2.6, C=4.3+/-0.6 ng/mL). Following ACTH administration, area under the cortisol response curve was greater (P=0.07) in the calm heifers. After declining below baseline concentrations during the post-challenge recovery period, cortisol in temperamental animals was again greater (P=0.02) than in the calm heifers. These data demonstrate that cattle with an excitable temperament exhibit increased stress responsiveness to handling, increased baseline adrenal function but not increased basal pituitary function, and a muted responsiveness to pharmacological stimulus. Thus, functional characteristics of the HPA axis vary with animal temperament.     

Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): priming the placental clock

The purposes of this study were to determine the intervals when placental corticotrophic-releasing hormone (CRH) was most responsive to maternal cortisol. A sample of 203 women each were evaluated at 15, 19, 25 and 31 weeks gestation and followed to term. Placental CRH and maternal adrenocorticotropin hormone (ACTH), B-endorphin and cortisol were determined from plasma. CRH levels increased faster and were higher in women who delivered preterm compared with women who delivered at term (F3,603 = 5.73, p < .001). Simple effects indicated that CRH levels only at 31 weeks predicted preterm birth (F1,201 = 5.53, p = .02). Levels of cortisol were higher in women who delivered preterm at 15 weeks gestation (F1,201 = 4.45, p = .03) with a similar trend at 19 weeks gestation. Hierarchical regression suggested that the influence on birth outcome of maternal cortisol early in pregnancy was mediated by its influence on placental CRH at 31 weeks. Elevated cortisol at 15 weeks predicted the surge in placental CRH at 31 weeks (R = .49, d.f. = 1,199, Fchange = 61.78, p < .0001). Every unit of change in cortisol (microg/dl) at 15 weeks was associated with a 34 unit change of CRH (pg/ml) at 31 weeks. These findings suggested that early detection of stress signals by the placenta stimulated the subsequent release of CRH and resulted in increased risk for preterm delivery.     

The effect of estradiol on output of adrenocorticotropin and prolactin by fetal sheep anterior pituitary cells

We examined the hypothesis that estradiol (E2) would affect fetal anterior pituitary corticotroph and lactotroph function in vitro, and that any effects would be influenced by gestational age. Anterior pituitary cells from fetal sheep at day 129 (n = 4) and at day 139 (n = 5) of gestation were cultured. After 96 h in culture, cells were treated for 18 h with E2 concentrations ranging from 0 to 1000 nM, in the presence or absence of 100 nM of corticotropin-releasing hormone (CRH), cortisol, arginine vasopressin (AVP), or CRH and cortisol, to examine their effects on corticotroph function. Cells were also treated with bromocriptine or increasing concentrations of E2 to study their effects on lactotroph function. Immunoreactive (ir) adrenocorticotropin (ACTH) and prolactin in the culture medium were measured by radioimmunoassay. Levels of cellular pro-opiomelanocortin (POMC) mRNA and prolactin mRNA were determined by in situ hybridization. Immunohistochemistry was used to determine the percentage of cells that were immunopositive for ACTH (corticotrophs) or prolactin (lactotrophs). ACTH output was stimulated by CRH treatment at day 139 but not at day 129 of gestation, and cortisol attenuated this response. ACTH output by cells cultured with 10 nM E2 and 100 nM CRH, at 139 days of gestation, was greater than with CRH alone (p < 0.05). E2 did not affect basal ACTH output or ACTH output with any other treatment or levels of POMC mRNA. Prolactin output was not affected by E2 treatment. Bromocriptine significantly decreased prolactin output but not levels of prolactin mRNA. We conclude that E2 may affect CRH-stimulated fetal sheep pituitary corticotroph function late in gestation, but only within a narrow, physiological range of concentration.     

Altered response to neuroendocrine challenge linked to indices of the metabolic syndrome in healthy adults

Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated with HDL cholesterol (p<0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease.     

Corticotropin-releasing hormone increases the expression of the prostaglandin E(2) receptor subtype EP1 in amnion WISH cells

The purpose of this study was to investigate the effect of corticotropin-releasing hormone (CRH) on the expression of the prostaglandin (PG) E(2) EP1 receptor subtype and PGE(2) production in amnion WISH cells (AWC). AWC cultures were incubated with CRH. Culture fluid was collected for PGE(2) measurement, and the cells were collected and analyzed for EP1 protein and mRNA. Immunohistochemical localization of the EP1 receptor was also performed. Incubation of AWC with CRH resulted in a dose-dependent increase (r = 0.97) in the level of EP1 receptor protein (P < 0.001). Coincubation of AWC with CRH and indomethacin resulted in the decreased production of PGE(2) while having no effect on EP1 receptor expression. A significant but not dose-dependent increase in EP1 mRNA expression was also observed (P < 0.01). Immunohistochemical evaluation verified cell membrane localization of the receptor in both stimulated and unstimulated cells and confirmed the increased expression of EP1 receptor in response to CRH. Incubation of AWC with CRH also resulted in increased culture fluid PGE(2) levels (P < 0.01). These results suggest that the role CRH plays in the initiation of labor may also involve the promotion of elevated PGE(2) levels and increased expression of the EP1 receptor in amnion.     

Prolonged exercise increases peripheral plasma ACTH, CRH, and AVP in male athletes

We wished to determine whether the increased ACTH duringprolonged exercise was associated with changes in peripheralcorticotropin-releasing hormone (CRH) and/or argininevasopressin (AVP). Six male triathletes were studied during exercise: 1 h at 70% maximal oxygen consumption, followed by progressivelyincreasing work rates until exhaustion. Data obtained during theexercise session were compared with a nonexercise control session.Venous blood was sampled over a 2-h period for cortisol, ACTH, CRH,AVP, renin, glucose, and plasma osmolality. There were significantincreases by ANOVA on log-transformed data in plasma cortisol(P = 0.002), ACTH(P < 0.001), CRH(P < 0.001), and AVP(P < 0.03) during exercise comparedwith the control day. A variable increase in AVP was observed after the period of high-intensity exercise. Plasma osmolality rose with exercise(P < 0.001) and was related toplasma AVP during submaximal exercise(P < 0.03) but not with theinclusion of data that followed the high-intensity exercise. Thisindicated an additional stimulus to the secretion of AVP. The mechanismby which ACTH secretion occurs during exercise involves both CRH andAVP. We hypothesize that high-intensity exercise favors AVP release andthat prolonged duration favors CRH release.

     

How to diagnose and manage Cushing's disease during pregnancy, when hypercortisolism is mild?

Diagnosis of mild Cushing's disease (CD) can be difficult in pregnant women, because its clinical and biochemical features can be erroneously interpreted as consequence of the gestation. Corticotropin releasing hormone (CRH) and desmopressin (DDAVP) tests are currently used to confirm CD, but data concerning adrenocorticotropic hormone (ACTH) response during pregnancy are lacking. A woman with mild cushingoid features was evaluated during the first trimester of gestation. Serum cortisol was normal at morning, but increased at midnight and incompletely suppressed by 1-mg dexamethasone overnight administration. Also 24-h urinary free cortisol levels were mildly elevated. She delivered vaginally a healthy newborn at the 39th week of an uneventful pregnancy. After delivery, an ACTH-secreting microadenoma was surgically removed. During the first trimester of gestation and after delivery, human CRH (h-CRH) and DDAVP-stimulated ACTH peaks were higher than those measured in 22 healthy premenopausal women. While the ACTH/h-CRH peak was intermediate between those measured in the healthy women and in 9 CD female patients, ACTH/DDAVP peak was in the range of CD patients and dramatically higher than those of healthy women. However, ACTH increase after h-CRH was significantly higher after delivery than during gestation (p?相似文献   

The inhibitory action of corticotropin-releasing hormone on gonadotropin secretion in the ovariectomized rhesus monkey is not mediated by adrenocorticotropic hormone

Earlier observations in our laboratory indicated that i.v. infusion of human/rat corticotropin-releasing hormone (hCRH) suppresses pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in ovariectomized rhesus monkeys. Since cortisol secretion increased significantly as well, it was not possible to exclude the possibility that this inhibitory effect of hCRH on gonadotropins was related to the activation of the pituitary/adrenal axis. The purpose of the present study was to determine the role of pituitary/adrenal activation in the effect of hCRH on LH and FSH secretion. We compared the effects of 5-h i.v. infusions of hCRH (100 micrograms/h, n = 7) and of human adrenocorticotropic hormone (ACTH) (1-24) (5 micrograms/h, n = 3; 10 micrograms/h, n = 3, 20 micrograms/h, n = 3) to ovariectomized monkeys on LH, FSH, and cortisol secretion. As expected, during the 5-h ACTH infusions, cortisol levels increased by 176-215% of baseline control, an increase similar to that observed after CRH infusion (184%). However, in contrast to the inhibitory effect observed during the CRH infusion, LH and FSH continued to be released in a pulsatile fashion during the ACTH infusions, and no decreases in gonadotropin secretion were observed. The results indicated that increases in ACTH and cortisol did not affect LH and FSH secretion and allowed us to conclude that the rapid inhibitory effect of CRH on LH and FSH pulsatile release was not mediated by activation of the pituitary/adrenal axis.     

Cortisol and ACTH responses to the Dex/CRH test: influence of temperament

Temperament and personality traits such as neuroticism and behavioral inhibition are prospective predictors of the onset of depression and anxiety disorders. Exposure to stress is also linked to the development of these disorders, and neuroticism and inhibition may confer or reflect sensitivity to stressors. Several lines of research have documented hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in some patients with major depression, as well as in children and non-human primates with inhibited temperaments. The present investigation tested the hypothesis that stress-reactive temperaments would be predictive of plasma adrenocorticotropin (ACTH) and cortisol concentrations in the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Sixty adults completed diagnostic interviews and questionnaires assessing the temperament domains of novelty seeking and harm avoidance and symptoms of anxiety and depression. All subjects were free of any current or past Axis I psychiatric disorder. The Dex/CRH test was performed on a separate visit. A repeated-measures general linear model (GLM) showed a main effect of harm avoidance in predicting cortisol concentrations in the test (F(1, 58)=4.86, p<.05). The GLM for novelty seeking and cortisol response also showed a main effect (F(1, 58)=5.28, p<.05). Higher cortisol concentrations were associated with higher levels of harm avoidance and lower levels of novelty seeking. A significant interaction of time with harm avoidance and novelty seeking (F(4, 53)=3.37, p<.05) revealed that participants with both high levels of harm avoidance and low levels of novelty seeking had the highest cortisol responses to the Dex/CRH test. Plasma ACTH concentrations did not differ as a function of temperament. The results indicate that temperament traits linked to sensitivity to negative stimuli are associated with greater cortisol reactivity during the Dex/CRH test. Increased adrenocortical reactivity, which previously has been linked to major depression and anxiety disorders, may contribute to the association between temperament/personality traits and these disorders.     

CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH

The response to systemic stress is organized along the hypothalamic-pituitary-adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation) is mediated by epidermal melanocytes (cells of neural crest origin) responsible for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC), corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can produce corticosterone. In the present study, incubation of normal epidermal melanocytes with CRH was found to trigger a functional cascade structured hierarchically and arranged along the same algorithm as in the HPA axis: CRH activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene expression and production of ACTH. CRH and ACTH also enhanced production of cortisol and corticosterone, and cortisol production was also stimulated by progesterone. The chemical identity of the cortisol was confirmed by liquid chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass spectrometry analyses. POMC gene silencing abolished the stimulatory effect of CRH on corticosteroid synthesis, indicating that this is indirect and mediated via production of ACTH. Thus the melanocyte response to CRH is highly organized along the same functional hierarchy as the HPA axis. This pattern demonstrates the fractal nature of the response to stress with similar activation sequence at the single-cell and whole body levels.     

Prevalence of endocrine dysfunction in HIV-infected men

OBJECTIVE: Endocrine dysfunction is a common problem in patients with human immunodeficiency virus infection (HIV). We therefore evaluated the endocrine function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4, TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS: Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed signs of latent hyperthyroidism (no response in TRH test). Adrenocortical function: Two patients had adrenal insufficiency. They showed a normal baseline cortisol level, an elevated ACTH level and no increase in cortisol levels after stimulation with CRH. All other patients revealed normal responses on the CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular insufficiency), 4 patients additionally had increased LH levels (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary hypogonadism (low LH and testosterone, increase of LH after stimulation with LH-RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary or tertiary origin, a substitution of hormones should be taken into consideration.