Adrenocorticotropin Hormone Concentrations Research Articles

Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

The Potential Role of Training Sessions on the Temporal and Spatial Physiological Patterns in Young Friesian Horses

This study compares the circulating adrenocorticotrophin hormone (ACTH), cortisol, lactate, glucose, heart rate, respiratory rate, rectal temperature, and blood count values in initially 2-year-old horses subjected to dressage training schedule during three consecutive days per 2 weeks. Sixteen healthy Friesian horses were used and were considered dressage group. Six healthy young horses not involved in training programs were used as control group. Blood sampling were collected from the jugular vein in baseline condition (dressage group and control group) and after exercise, within 5 minutes of the end of the training session (dressage group). Compared to baseline values, results showed higher ACTH concentrations after the first day of the first training week (P < .005) and after the third day of the second week (P < .005); higher lactate concentrations after the second and the third day of the second week (P < .01); lower glucose concentrations after the third day of the first week (P < .01); higher HR, RR, and RT values and lower PLT count after different time points during both training weeks. One-way ANOVA showed significant training effect for ACTH (F = 7.605; P < .0001) and glucose (F = 3.505; P < .001) concentrations over time points. Two-way ANOVA showed a significant effect of dressage training sessions between the first and the second week for ACTH (F = 6.508; P < .001) and cortisol (F = 5.559; P < .0001) concentrations. From obtained data, it seems that the use of ACTH and cortisol changes for the assessment of effects of training in initially 2-year-old horses could be an ideal measure of quantitative and qualitative stress responses. The quantification at the same time of functional responses to stressful stimuli may offer a more objective measurement of dressage training effects.

Paternal calorie restriction prior to conception alters anxiety-like behavior of the adult rat progeny

The maternal environment influences a broad range of phenotypic outcomes for offspring, with anxiety-like behavior being particularly susceptible to maternal environmental perturbations. Much less is known regarding paternal environmental influences. To investigate this, adult male rats were exposed to 25% calorie restriction (CR) or glucocorticoid elevation (CORT; 200μg/ml of corticosterone in drinking water) for ∼6 weeks prior to breeding. Elevated plus maze (EPM), open field (OF), predator odor (cat urine), and acoustic startle/pre-pulse inhibition (AS/PPI) were characterised in the adult male offspring. Plasma concentrations of corticotrophin-releasing hormone (CRF), adrenocorticotropin hormone (ACTH), and serum lepin were characterised in both sires and offspring. Maternal care received by litters was additionally observed. Expectedly, CR and CORT treatment attenuated weight gain, whilst only CR induced anxiolytic behavior in the EPM. The adult offspring sired by CR males also demonstrated a reduction in weight gain, food intake and serum leptin levels when compared to controls. Moreover, CR offspring demonstrated an anxiolytic-like profile in the EPM and OF, enhanced habituation to the AS pulse, reduced PPI, but no alteration to predator odor induced defensiveness compared to control. CORT offspring failed to demonstrate any behavioral differences from controls, however, exhibited a trend towards reduced ACTH and leptin concentration. Collectively, the results indicate that a reduction in calories in males prior to conception can affect the behavior of adult offspring. The phenotypic transmission of CR experiences from fathers to the progeny could potentially be mediated epigenetically. The role of glucocorticoid elevation and maternal care are also discussed.

Paradoxical Results after Inadvertent Use of Cosyntropin [Adrenocorticotropin Hormone (1-24)] Rather than Acthrel (Ovine Corticotropin Releasing Hormone) during Inferior Petrosal Sinus Sampling

The use of ovine corticotropin releasing hormone (oCRH) maximizes the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel) during IPSS may cause unexpected and misleading results. The aim of this report is to raise awareness of the potential confounding results created when synthetic ACTH(1-24) is mistakenly used during IPSS. We present 3 patients treated at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly substituted for oCRH (ACTHrel) during IPSS. In all patients, there was an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used rather than oCRH during each procedure. Because "sandwich" immunometric assays for ACTH measure the entire pool of endogenous ACTH, the administration of synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39) measurement by binding only to the N-terminal antibody raised against ACTH(1-17) and not to the C-terminal antibody raised against ACTH(34-39). This results in a lack of a detectable sandwich complex and explains the apparent reduction in ACTH concentration. An abrupt decrease in ACTH during IPSS suggests that synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The labeling of oCRH as ACTHrel poses a potential patient safety problem about which endocrinologists, interventional radiologists, and pharmacists should be aware.

Effects of resistance exercise on the HPA axis response to psychological stress during short-term smoking abstinence in men

PurposeThe purpose of this study was to examine the effects of resistance exercise on the hypothalamic–pituitary–adrenal axis (HPA) response to mental challenge, withdrawal symptoms, urge to smoke, and cognitive stress during 24-hour smoking abstinence. Methods8 sedentary smokers (mean±SD age: 20.1±1.7y; height: 171.6±10.8cm; body mass: 70.4±12.0kg; smoking history: 2.9±0.8y) completed a 24-hour ad libitum smoking trial (SMO) followed by two 24-hour smoking abstinence trials. During abstinence trials, participants performed six whole body resistance exercises (EX) or a control condition (CON) in the morning, followed by mental challenge tasks in the afternoon. Plasma adrenocorticotropin hormone (ACTH), and salivary and serum cortisol were measured during each visit at rest (REST), and then before (PRE-EX), immediately after (IP-EX), and 30min after exercise (30-EX); and before (PRE-MC), immediately after (IP-MC), and 30min after mental challenge (30-MC). ResultsResistance exercise significantly (p≤0.05) elevated plasma ACTH and serum cortisol at IP-EX during EX compared with SMO and CON trials. Resting ACTH, salivary and serum cortisol concentrations at Pre-MC did not differ between EX and CON trials. The HPA axis response to mental challenge was similar after EX and CON trials. Finally, resistance exercise did not reduce withdrawal symptoms, urge to smoke, or stress. ConclusionResistance exercise did not substantially alter resting HPA hormones or the HPA response to mental challenge tasks during 24h of smoking abstinence.

Acute incremental exercise, performance of a central executive task, and sympathoadrenal system and hypothalamic-pituitary-adrenal axis activity

The purposes of this study were to examine the effect of acute incremental exercise on the performance of a central executive task; the responses of the sympathoadrenal system (SAS) and hypothalamic-pituitary-adrenal axis (HPAA) during exercise, while simultaneously carrying out the central executive task; and the ability of Δ plasma concentrations of epinephrine, norepinephrine, adrenocorticotropin hormone (ACTH) and cortisol to predict Δ performance on the central executive task. Subjects undertook a flanker task at rest and during exercise at 50% and 80% maximum aerobic power (MAP). SAS and HPAA activity were measured pre- and post-treatment by plasma concentrations of catecholamines, and cortisol and ACTH, respectively. Reaction time (RT) and number of errors for congruent and incongruent trials on the flanker task showed significant main effects with performance at 80% MAP higher than in the other conditions. RT post-correct responses were significantly faster than RT post-error at rest and 50% MAP but not at 80%. Pre- and post-treatment catecholamines showed a main effect of exercise with a linear increase. Post-treatment ACTH concentrations at 80% MAP were significantly greater than in the other conditions. Δ epinephrine and ACTH combined were significant predictors of Δ RT and Δ norepinephrine was a significant predictor of Δ number of errors. It was concluded that exercise must be at a high intensity to affect performance on the flanker task. Both the SAS and HPAA appear to play a role in the exercise–cognition interaction.

Blood Arginine Vasopressin, Adrenocorticotropin Hormone, and Cortisol Concentrations at Admission in Septic and Critically Ill Foals and their Association with Survival

Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.

Relationship Between Plasma Adrenocorticotropin Hormone and Intensive Care Unit Survival in Early Traumatic Brain Injury

Hypothalamic pituitary adrenal response has been recently evaluated in patients with traumatic brain injury (TBI) with different results. Our objective was to study this response and its relationship with outcome in the early stage after TBI. We conducted a prospective observational clinical study in the intensive care unit of a tertiary level university hospital. The study included 50 consecutive patients who suffered isolated TBI. Intracranial pressure (ICP) was measured by an intraparenchymal probe. All patients were sedated and mechanically ventilated. Second-level measures were provided as per protocol, when needed. We measured plasma adrenocorticotropin hormone (ACTH) levels, as well as baseline and stimulated serum cortisol after a high-dose corticotrophin stimulation test, within 2 days after TBI for all patients. Mean age was 36 +/- 18 (range 16-77) years. Forty-four (88%) were male. Median Glasgow Coma Scale score was 7. Mean ACTH was 15.4 +/- 19.8 pg/mL. Mean baseline cortisol was 14.8 +/- 9.0 microg/dL and mean stimulated cortisol was 27.1 +/- 7.3 microg/dL and 30.5 +/- 7.2 microg/dL at 30 and 60 minutes, respectively. Baseline and stimulated cortisol were not correlated with mortality. Logistic regression analysis revealed that, either plasma ACTH levels <9 pg/mL or lack of indication to provide second-level measures to control ICP were significant independent predictors of survival. The presence of a low plasma ACTH concentration at an early stage of TBI and lack of indication to provide second-level measures to control ICP were associated with a higher intensive care unit survival.

Comparison of the hypothalamic–pituitary–adrenal axis in MDR1‐1Δ and MDR1 wildtype dogs

AbstractObjective: To evaluate the hypothalamic–pituitary–adrenal (HPA) axis in MDR1‐1Δ (dogs with the MDR1 mutation associated with ivermectin sensitivity) and MDR1 wildtype dogs.Design: Prospective study.Setting: Institutional vivarium.Animals: Seven healthy Collie dogs.Measurements: MDR1 genotyping was used for allocation of dogs to 1 of 2 groups: dogs homozygous for the wildtype MDR1 allele (MDR1 wildtype) and those homozygous for the MDR1‐1Δ mutation (MDR1 mutant). Blood samples were obtained for determination of cortisol and adrenocorticotropin hormone (ACTH) concentrations under basal conditions, before and after ACTH administration, and before and after dexamethasone administration.Main results: Significant differences were identified between the MDR1 mutant and MDR1 wildtype groups. Basal plasma cortisol concentrations and cortisol concentrations after ACTH administration were significantly lower in MDR1 mutant dogs as compared with MDR1 wildtype dogs. Plasma ACTH concentrations after dexamethasone administration were significantly lower in MDR1 mutant dogs as compared with MDR1 wildtype dogs.Conclusions: Results suggest that P‐glycoprotein (P‐gp) plays a role in regulation of the HPA axis. Furthermore, it appears that the HPA axis in MDR1 mutant dogs that lack P‐gp is suppressed compared with MDR1 wildtype dogs. This finding may explain some clinical observations in breeds known to harbor the MDR1 mutation including Collies, Shelties, Australian Shepherds, and others. There is a clinical impression that many of these dogs have worse outcomes in response to stress and, at times, respond poorly to appropriate therapy. HPA axis suppression, secondary to the MDR1 mutation, could result in a relative adrenal insufficiency (RAI) state during times of stress or illness. Further studies are required to determine the relationship between the MDR1 genotype and RAI.

Plasma Pro‐opiomelanocortin, Pro‐adrenocorticotropin Hormone, and Pituitary Adenoma Size in Dogs with Cushing's Disease

It is difficult to predict the size of pituitary corticotroph tumors in dogs with Cushing's disease (pituitary‐dependent hyperadrenocorticism [PDH]) without pituitary imaging techniques. The purpose of this study was to examine the relationship between plasma adrenocorticotropin hormone (ACTH) precursor concentration and pituitary size in dogs with Cushing's disease. Plasma concentrations of ACTH precursors (pro‐opiomelanocortin [POMC]/pro‐ACTH) and pituitary tumor height/brain area were measured in 36 dogs with pituitary corticotroph adenomas of various sizes. There was a correlation between tumor size (measured as the pituitary tumor height/brain area ratio [P/B]) and POMC/pro‐ACTH concentration (r= .70; P&lt; .0001). Dogs with P/B &lt; 0.40 × 10‐2 mm‐1 had higher concentrations of ACTH precursors than dogs with P/B &lt; 0.40 × 10‐2 mm‐1 (median concentration 85 pmol/L, range 15‐1,350 pmol/L, n = 14 versus 15 pmol/L, range 15–108 pmol/L, n = 22; P &lt; .0001). With a threshold of 35 pmol/L of POMC/pro‐ACTH concentration, the estimated sensitivity and specificity of the kit were 93% (95% confidence interval [CI], 79–100%) and 86% (95% CI, 73–100%), respectively. We interpret these data as indicating that measurement of POMC and pro‐ACTH might be of value in the characterization of tumor size in dogs with Cushing's disease. Low POMC/pro‐ACTH concentrations make it unlikely that a large pituitary tumor exists in dogs with PDH.

ACTH enhances chondrogenesis in multipotential progenitor cells and matrix production in chondrocytes

The association of melanocortin peptide overproduction with enhanced linear growth prompted the current investigation of adrenocorticotropin hormone (ACTH) effects on multipotential chondroprogenitor populations and committed chondrocytes in culture. Two multipotential progenitor populations, rat bone marrow stromal cells (BMSC) and the clonal multipotential cell line RCJ3.1, and two committed chondrocyte populations, resting chondrocytes (RC) isolated from the rib of young rats and the chondrocyte restricted cell line RCJ3.1C5.18 (C5.18), were cultured in differentiation medium plus or minus ACTH. Alcian blue stain was used to quantitate proteoglycan matrix production in all populations treated with a range of ACTH concentrations. Changes in proliferation due to ACTH treatment of all cell types were measured using 3H-thymidine incorporation. Differences in matrix production of ACTH-treated and -untreated RC and C5.18 cells were determined using 3H-proline incorporation. Relative transcript expression of the chondrocyte matrix proteins collagen type II (COLL II) and aggrecan (AGR) in treated and untreated cells was analyzed by Northern blot. Collagen type X (COLL X), a marker of hypertrophic differentiation, was measured in committed chondrocytic populations. Western analysis was used to detect the melanocortin-3 receptor (MC3-R), which was a suspected mediator of the ACTH signal. Matrix deposition was dose-dependently increased by ACTH in all cell populations as measured by alcian blue stain. ACTH treatment increased proliferation in multipotential progenitor populations (BMSC and RCJ3.1) while proliferation was decreased in committed chondrocyte populations (RC and C5.18). Total protein and total cell-associated collagen production were significantly increased by ACTH treatment in committed populations. Relative COLL II and AGR transcript expressions were significantly increased in both the RC- and C5.18-committed population and very significantly increased in the progenitor populations. Additionally, collagen type X expression was detected earlier and in greater abundance in ACTH-treated committed chondrocyte populations. Finally, the melanocortin-3 receptor was detected in all examined cell types by Western blot. These data show that ACTH promotes the development of the chondrocyte phenotype from multipotential mesenchymal progenitor populations and increases matrix production and differentiation of committed chondrocytes. These findings, together with the detection of the MC3-R in all of these cell types, indicate a role for the melanocortin system in chondrogenesis.

Adenosine A2A receptor gene disruption provokes marked changes in melanocortin content and pro-opiomelanocortin gene expression.

A2A receptor knockout (A2AR-/-) mice are more anxious and aggressive, and exhibit reduced exploratory activity than their wild-type littermates (A2AR+/+). Because alpha-melanocyte-stimulating hormone (alpha-MSH) influences anxiety, aggressiveness and motor activity, we investigated the effect of A2AR gene disruption on alpha-MSH content in discrete brain regions and pro-opiomelanocortin (POMC) expression in the hypothalamus and pituitary. No modification in alpha-MSH content was observed in the hypothalamus and medulla oblongata where POMC-expressing perikarya are located. In the arcuate nucleus of the hypothalamus, POMC mRNA levels were not affected by A2AR disruption. Conversely, in A2AR-/- mice, a significant increase in alpha-MSH content was observed in the amygdala and cerebral cortex, two regions that are innervated by POMC terminals. In the pars intermedia of the pituitary, A2AR disruption provoked a significant reduction of POMC mRNA expression associated with a decrease in alpha-MSH content. By contrast, in the anterior lobe of the pituitary, a substantial increase in POMC mRNA and adrenocorticotropin hormone concentrations was observed, and plasma corticosterone concentration was significantly higher in A2AR-/- mice, revealing hyperactivity of their pituitary-adrenocortical axis. Together, these results suggest that adenosine, acting through A2A receptors, may modulate the release of alpha-MSH in the cerebral cortex and amygdala. The data also indicate that A2A receptors are involved in the control of POMC gene expression and biosynthesis of POMC-derived peptides in pituitary melanotrophs and corticotrophs.

Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in ewes.

This study used the novel approach of statistical modelling to investigate the control of hypothalamic-pituitary-adrenal (HPA) axis and quantify temporal relationships between hormones. Two experimental paradigms were chosen, insulin-induced hypoglycaemia and 2 h transport, to assess differences in control between noncognitive and cognitive stimuli. Vasopressin and corticotropin-releasing hormone (CRH) were measured in hypophysial portal plasma, and adrenocorticotropin hormone (ACTH) and cortisol in jugular plasma of conscious sheep, and deconvolution analysis was used to calculate secretory rates, before modelling. During hypoglycaemia, the relationship between plasma glucose and vasopressin or CRH was best described by log10 transforming variables (i.e. a positive power-curve relationship). A negative-feedback relationship with log10 cortisol concentration 2 h previously was detected. Analysis of the "transport" stimulus suggested that the strength of the perceived stimulus decreased over time after accounting for cortisol facilitation and negative-feedback. The time course of vasopressin and CRH responses to each stimulus were different However, at the pituitary level, the data suggested that log10 ACTH secretion rate was related to log10 vasopressin and CRH concentrations with very similar regression coefficients and an identical ratio of actions (2.3 : 1) for both stimuli. Similar magnitude negative-feedback effects of log10 cortisol at -110 min (hypoglycaemia) or -40 min (transport) were detected, and both models contained a stimulatory relationship with cortisol at 0 min (facilitation). At adrenal gland level, cortisol secretory rates were related to simultaneously measured untransformed ACTH concentration but the regression coefficient for the hypoglycaemia model was 2.5-fold greater than for transport. No individual sustained maximum cortisol secretion for longer than 20 min during hypoglycaemia and 40 min during transport. These unique models demonstrate that corticosteroid negative-feedback is a significant control mechanism at both the pituitary and hypothalamus. The amplitude of HPA response may be related to stimulus intensity and corticosteroid negative-feedback, while duration depended on feedback alone.

Effects of vitamin E and selenium on thyroid status, adrenocorticotropin hormone, and blood serum metabolite and mineral concentrations of Japanese quails reared under heat stress (34°C)

AbstractThis study was conducted to determine the effects of vitamin E and selenium (Se) on triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), adrenocorticotropin hormone (ACTH), and serum glucose, urea, triglyceride, cholesterol, Ca, P, Na, and K concentrations of Japanese quails reared under heat stress (34°C). One‐hundred twenty 10‐day‐old Japanese quails were randomly assigned to four treatment groups with three replicates of 10 birds each. The birds with a 2 × 2 factorial design received either two levels of vitamin E (125 and 250 mg/kg of diet) or two levels of selenium (0.1 and 0.2 mg/kg of diet). Greater dietary vitamin E and selenium inclusions resulted in a greater (P = 0.001) serum T3, T4, and TSH, but lower (P = 0.001) ACTH concentrations. No interactions between vitamin E and selenium were detected (P ≥ 0.11) for serum concentrations of T3, T4, TSH, and ACTH. Serum glucose, urea, triglyceride, and cholesterol concentrations decreased (P = 0.001), whereas protein concentrations increased (P = 0.001) when both dietary vitamin E and selenium increased. Serum albumin concentrations increased (P = 0.001) with greater dietary vitamin E but did not change with dietary selenium (P = 0.16). No interactions on any blood metabolites were detected (P ≥ 0.11). Serum activities of serum glutamic oxalate transaminase and serum glutamic pyruvate transaminase were not influenced by dietary vitamin E or selenium (P ≥ 0.42). However, serum activity of alkaline phosphatase increased (P = 0.001) with both increasing dietary vitamin E and selenium. There were no interactions detected for the serum enzyme activities (P ≥ 0.09). Increasing both dietary vitamin E and selenium caused an increase in serum concentrations of Ca, P, and K (P = 0.001), but a decrease in serum concentrations of Na (P = 0.001). No interactions were detected for serum mineral concentrations (P ≥ 0.07) except for P (P = 0.001). Results of the present study showed that dietary vitamin E and selenium have synergistic effects, and that supplementing a combination of dietary vitamin E (250 mg) and selenium (0.2 mg) positively influences some blood parameters that may positively influence the performance of Japanese quails under heat stress. J. Trace Elem. Exp. Med. 16:95–104, 2003. © 2003 Wiley‐Liss, Inc.

No Effect of a Selective Serotonergic/Noradrenergic Reuptake Inhibitor on Endurance Performance

The purpose of the present study was to examine the effects of a selective serotonin/noradrenaline (5-HT/NA) reuptake inhibitor (SNRI) on exercise performance. Seven well-trained male cyclists completed 2 time trials in a doubleblind randomized crossover design ingesting either placebo (PLAC) or 2 × 37.5 mg of Venlafaxine (VEN). Blood samples were collected for adrenocorticotropin hormone (ACTH), prolactin (PRL), cortisol, growth hormone (GH), beta-endorphins, and catecholamines and were taken at rest, at 30-min time intervals, at the end of exercise, and during recovery. Performance was not influenced by the SNRI (VEN: 92 min ± 3 min, PLAC: 92 min ± 1 min). Lactate concentrations, heart rate, and fatigue scores were not different between trials. All hormones increased during exercise in both trials. In the VEN trial, ACTH, beta endorphins, and NA concentrations were higher. The results from the present study demonstrate that a SNRI is not able to affect endurance performance in well-trained cyclists. However, it seems as though the hormonal response to the combination of the pharmacological manipulation and exercise is regulated more by the noradrenergic drive.

Multiple Versus Single Courses of Antenatal Corticosteroids for Preterm Birth: A Pilot Study

Objectives: (1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS) more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.Methods: Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.Results: Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.Conclusion: A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study Protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible.

Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats.

In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.

Opioid and cannabinoid receptor-mediated regulation of the increase in adrenocorticotropin hormone and corticosterone plasma concentrations induced by central administration of Δ 9-tetrahydrocannabinol in rats

The purpose of this study was to investigate the cannabinoid and opioid mediated regulation on the effects of central Δ 9-tetrahydrocannabinol (Δ 9-THC) administration on hypothalamus–pituitary–adrenal (HPA) axis activity in the male rat. Intracerebroventricular (i.c.v.) administration of Δ 9-THC (25, 50, 100 μg/rat) markedly increased plasma adrenocorticotropin hormone (ACTH) and corticosterone concentrations. Time course effect studies revealed that both hormones secretion peaked at 60 min after Δ 9-THC i.c.v. administration (50 μg/rat), decreased gradually and returned to baseline levels by 480 min. The i.c.v. administration of the specific cannabinoid receptor antagonist SR-141716A (3 μg/rat) significantly attenuated the increase of both hormones secretion induced by Δ 9-THC (50 μg/rat). Nevertheless, higher doses (12.5 and 50 μg/rat) of this compound increased both ACTH and corticosterone plasma concentrations. Subcutaneous (s.c.) administration with the opiate receptor antagonist naloxone (0.3 mg/kg) was without effect but significantly diminished the increase of both hormones secretion induced by Δ 9-THC (50 μg/rat). Taken together, these results indicate that opiate and cannabinoid receptors are involved in the activation of the HPA axis induced by Δ 9-THC. Furthermore, the increase of ACTH and corticosterone secretion after the administration of higher doses of SR-141716A than those required to block such activation, suggests that endogenous cannabinoids are tonically inhibiting the release of both hormones or that this agonist-like activity may be part of an uncharacterized action of this compound not mediated by cannabinoid receptors.

Fall and Winter Hormone Concentrations Related to Stress in Pigs Identified as Normal and Carrier for Stress Susceptibility

Stress is associated with significant losses in the swine industry. Seasonal changes have been shown to affect stress resistance in several species of animals. In the present study, we examined the effect of two seasons (fall or winter) on plasma insulin, Cortisol, and adrenocorticotrophin hormone (ACTH) levels from fasted normal and carrier pigs for stress susceptibility when submitted to a blood-sampling stressor between 10:00 and 11:00. Comparisons were made of 10 diurnally active normal (NN) and 8 carrier (Nn) pigs reared in the fall to 9 NN and 10 Nn pigs reared in the winter. The light-dark cycle throughout the period of the experiment was 10h light/14h dark, with lights on from 07:00 to 17:00. Feed consisted of the traditional western Canadian swine ration consumed ad libitum. Results revealed significant season-by-genotype interactions for plasma insulin and ACTH concentrations in response to the blood-sampling stressor. The normal pigs displayed a significantly lower plasma insulin level during winter compared to the fall season. Plasma ACTH of normal pigs was 18% lower in the winter compared to the fall season, although this difference was not statistically significant. The carrier genotype, on the other hand, demonstrated higher plasma insulin concentration and lower plasma ACTH concentration in the winter compared to the fall season. Furthermore, there was a main genotype effect in plasma Cortisol concentration such that the carrier pigs experienced a greater level compared to the normal genotype. Similarly, the carrier pigs had a more acute ACTH response to the blood-sampling stressor compared to the normal pigs during the fall season. Results have demonstrated that these two seasons of the year affect the response of both genotypes to a blood-sampling stressor, with the carrier genotype experiencing a more intense stress reaction in the fail season. These results further contribute to the recent research indicating that carrier pigs for stress susceptibility have a unique stress response.

Superior cervical ganglionectomy suppresses circadian corticotropic rhythms in male rats in the short term (5 days) and long term (10 days)

Superior cervical ganglionectomy (SCGx) has drastic effects on numerous hormonal circadian rhythms and particularly on pineal melatonin secretion. We investigated the hormonal consequences of ablation of the superior cervical ganglion on the corticotropic circadian rhythms in the male rat. Plasma were obtained by sampling blood every 4 h, using a chronic carotid cannula. Adreno-corticotropin hormone (ACTH) was assayed by radioimmunoassay (RIA) and corticosterone (B) by radiocompetition. Urinary 6-sulphatoxymelatonin (aMT6s), considered as an index of the pineal gland activity, was assayed by specific RIA: a decrease in the aMT6s concentration after ganglionectomy was taken as proof of adequate surgical operation. Control animals showed classical circadian rhythms for ACTH and B with basal values during the light phase and circadian peaks around the light/dark interface. Five and ten days after ganglionectomy, the circadian rhythms of ACTH and B were suppressed. In addition, the mean ACTH concentrations increased significantly 10 days after ganglionectomy compared to those in sham-operated rats and 5 days post-operation group. The mean plasma corticosterone levels were similar in those three groups of animals. This is the first study demonstrating the supressive effect of superior cervical ganglionectomy on the circadian corticotropic hormonal cycle.