Plasma profiles of prolactin, growth hormone, adrenocorticotropic hormone (ACTH) and cortisol were evaluated in a group of untreated patients with idiopathic Parkinson's disease and a group of healthy age-matched controls. Plasma integrated concentrations of all hormones except prolactin were significantly lower in the patients as compared with the controls; however, prolactin nocturnal peak concentration was significantly elevated in the patients;
G. Bellomo; L. Santambrogio; M. Fiacconi; A. M. Scarponi; G. Ciuffetti
The aim of the study was to evaluate the effect of adrenal stimulation by adrenocorticotropic hormone (ACTH) on blood cortisol\\u000a concentration and on circulating total and differential leukocyte counts during and in the 16 days after ACTH administration.\\u000a Swedish Landrace boars aged approximately 6–7 months were used. ACTH-treated animals (n = 7) were given ACTH intravenously at 10 ?g\\/kg body
N. Bilandži?; M. Žuri?; M. Lojki?; B. Šimi?; D. Mili?; I. Bara?
Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA) axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH) levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated) and ACTH. In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032) and stimulated cortisol (p = 0.04) and higher ACTH (p = 0.01) than controls. Childhood Autism Rating Scale (CARS) score correlated positively with ACTH (r = 0.71, p = 0.02) and negatively with each of basal (r = -0.64, p = 0.04) and stimulated cortisol (r = -0.88, p < 0.001). Hormonal profile did not differ in relation to EEG abnormalities, IQ and self- aggressive symptoms. Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.
Objectives: To investigate the changes in adrenocorticotropic hormone (ACTH) and cortisol in heroin addicts given Jitai tablet treatment during abstinence. Design: Double-blind, randomized, placebo-controlled clinical trial. Settings/Location: Drug Rehabilitation Bureau of Shanghai Police, China. Participants: 99 volunteers, including 69 heroin addicts and 30 healthy volunteers. Interventions: 69 heroin addicts randomly divided into two groups: the Jitai tablet group, which comprised 34 heroin addicts given Jitai tablet treatment during abstinence, and the placebo group, which comprised 35 heroin addicts given placebo. A control group consisted of 30 sex- and age-matched healthy volunteers. Outcome Measures: ACTH and cortisol in plasma were measured in all groups at baseline and in the Jitai tablet and placebo groups on the third, seventh, and 14th days of abstinence. Results: Levels of both ACTH (p<.01) and cortisol (p<.001) were significantly higher in heroin addicts at baseline than in the healthy volunteers. Jitai tablet treatment restored plasma cortisol levels to normal more rapidly than did placebo treatment (p<.05), but not ACTH levels. A positive correlation between ACTH and cortisol values at baseline (p<.01) was also found with withdrawal symptom scores and daily dosages of heroin. Conclusions: Heroin addicts could respond to Jitai tablets through changes in the hypothalamus-pituitary-adrenal axis. PMID:24786196
Fan, Hua-Ying; Sun, Li; Li, Xiao-Xiao; Zhou, Shao-Bo; Liang, Jun-Cheng; Yan, Ben-Yong; Li, Yu; Deng, Yan-Ping
Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been reported to be involved in vulnerability to alcohol and drug dependence in humans, possibly underlying both addictive behaviour and depression susceptibility. The aim of the present study was to investigate the possible interactions between childhood adverse experiences, depressive symptoms and HPA axis function in addicted patients, in comparison with healthy control. Eighty-two abstinent heroin or cocaine dependent patients and 44 normal controls, matched for age and sex, completed the symptoms Check List-90 (SCL-90), measuring depressive symptoms, and the Childhood Experience of Care and Abuse Questionnaire. Blood samples were collected to determine adrenocorticotropic hormone (ACTH) and cortisol basal plasma levels at 8:00 and 8:30 a.m. Addicted individuals showed significantly higher neglect and depression scores and ACTH-cortisol plasma levels respect to control subjects. Depression scores at SCL-90 in addicted patients positively correlated with plasma ACTH and cortisol values. In turn, plasma ACTH levels were directly associated with childhood neglect measures, reaching statistical significance with 'mother-neglect' scores. Plasma cortisol levels were related to 'father antipathy' among cocaine addicts. These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may have a persistent effect on HPA axis function as an adult, partially contributing, together with genetic factors and other environmental conditions, to both depressive traits and substance abuse neurobiological vulnerability. PMID:18201294
Gerra, Gilberto; Leonardi, Claudio; Cortese, Elena; Zaimovic, Amir; Dell'Agnello, Grazia; Manfredini, Matteo; Somaini, Lorenzo; Petracca, Francesca; Caretti, Vincenzo; Baroni, Cristina; Donnini, Claudio
Relative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 ?g tetracosactide intravenous injection. Patients were divided into two groups: responders (? [T60 minus baseline] total cortisol >9 ?g/dL) and nonresponders (? total cortisol ?9 ?g/dL or baseline total cortisol <10 ?g/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide. PMID:24667620
Festti, Josiane; Grion, Cintia Magalhães Carvalho; Festti, Luciana; Mazzuco, Tânia Longo; Lima-Valassi, Helena Pantelion; Brito, Vinícius Nahime; Barbosa, Décio Sabbatini; Carrilho, Alexandre José Faria
Vibration, being a consequence of mo- tion during transport, may impair the welfare of pigs. Therefore, the primary objectives of this study were 1) to evaluate during transport simulation the use of ACTH and cortisol plasma levels, which are part of a basic adaptation mechanism of pigs and 2) to define comfort conditions for pigs related to the frequency and
S. Perremans; J. M. Randall; G. Rombouts; E. Decuypere; R. Geers
Introduction Isolated adrenocorticotropic hormone deficiency is an endocrinological disorder characterized by loss of adrenocorticotropic hormone and resultant adrenal insufficiency. Affected patients often present with fatigue, anorexia, and hyponatremia. Although the number of reported cases has been recently increasing, isolated adrenocorticotropic hormone deficiency combined with malignant neoplasia is very rare. Here we describe a patient with gastric cancer who developed unexpected isolated adrenocorticotropic hormone deficiency during chemotherapy. Case presentation A 72-year-old Japanese man was admitted to our hospital because of febrile neutropenia due to chemotherapy for gastric cancer recurrence. Although the neutropenia and fever immediately improved, he became unable to take any oral medications and was bedridden 1 week after admission. His serum sodium level abruptly decreased to 122mEq/L on the fifth day of hospitalization. We performed endocrinological studies to investigate the cause of his hyponatremia and plasma hyposmolality. His plasma adrenocorticotropic hormone and cortisol levels were very low. However, his serum levels of all other anterior pituitary hormones were slightly elevated. We then performed a corticotropin-releasing hormone test, which showed that neither his plasma adrenocorticotropic hormone nor cortisol level responded to corticotropin-releasing hormone stimulation. We definitively diagnosed isolated adrenocorticotropic hormone deficiency based on these findings. Hydrocortisone replacement therapy was begun at 20mg/day, resulting in a marked improvement in his anorexia and general fatigue within a few days. His serum sodium level was also normalized immediately after the administration of hydrocortisone. He was discharged from our hospital on the 50th day of hospitalization. Conclusions The present case is the second report of a patient with concurrent isolated adrenocorticotropic hormone deficiency and gastric cancer and the first report of a patient diagnosed with isolated adrenocorticotropic hormone deficiency during the course of chemotherapy for a solid malignant neoplasm. Although the symptoms and signs described in the present report are common observations during chemotherapy, it is important to consider not only the adverse effects of antineoplastic agents, but also isolated adrenocorticotropic hormone deficiency as a differential diagnosis. Hydrocortisone replacement therapy for isolated adrenocorticotropic hormone deficiency effectively avoids the unnecessary cessation of chemotherapy.
Ocular hypertension caused by endogenous Cushing syndrome from an ectopic adrenocorticotropic hormone-producing tumor is rare. We report an 11-year-old boy who presented with intraocular pressures (IOPs) of 50 mm Hg in both eyes. Surgical resection of the tumor was performed with subsequent normalization of serum cortisol and IOP levels. PMID:20637667
Khaw, Keat Ween; Jalaludin, Muhammad Yazid; Suhaimi, Hussain; Harun, Fatimah; Subrayan, Visvaraja
Hypertension is a prominent feature of patients with Cushing's disease and ectopic adrenocorticotropic hormone (ACTH) syndrome, who have elevated ACTH levels. Chronic administration of ACTH (1-24) also raises blood pressure in humans. This effect has been postulated to be due to ACTH-induced increases in cortisol secretion in the adrenal gland. It is well known that cortisol increases vascular tone by
Haruhiko Hatakeyama; Satoru Inaba; Naomi Taniguchi; Isamu Miyamori
Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol
J. H. Kyllo; M. M. Collins; K. L. Vetter
...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1025 Adrenocorticotropic hormone (ACTH) test system. (a)...
The purpose of this study was to investigate total baseline plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations, and ACTH-stimulated cortisol concentrations in foals from birth to 12 wk of age. Plasma (baseline) cortisol and ACTH concentrations were measured in 13 healthy foals at birth and at 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, 56, and 84 d of age. Each foal received cosyntropin (0.1 ?g/kg) intravenously. Plasma cortisol concentrations were measured before (baseline), and 30, and 60 min after cosyntropin administration at birth and at 3, 5, 7, 10, 14, 21, 28, 42, 56, and 84 d of age. Compared with baseline, cortisol concentration increased significantly 30 min after administration of cosyntropin on all days. Cortisol concentration was highest at birth, measured at 30 and 60 min after cosyntropin administration, compared with all other days. With the exception of birth measurements, cortisol concentration was significantly higher on day 84, measured at 30 and 60 min after cosyntropin administration, when compared with all other days. Baseline plasma ACTH was lowest at birth when compared with concentrations on days 2, 3, 4, 5, 7, 10, 14, 42, 56, and 84. Administration of 0.1 ?g/kg of cosyntropin, IV, reliably induces cortisol secretion in healthy foals. Differences in the magnitude of response to cosyntropin are observed depending on the age of the foal. These data should serve as a reference for the ACTH stimulation test in foals and should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill foals.
Wong, David M.; Vo, Dai Tan; Alcott, Cody J.; Stewart, Allison J.; Peterson, Anna D.; Sponseller, Brett A.; Hsu, Walter H.
Enhanced Suppression of Adrenocorticotropic Hormone and Cortisol Responses to Hypothalamic-Pituitary-Adrenal Function and Thyrotropin-Releasing Hormone Tests after Stressful Life Events in Patients with Major Depressive Disorder
Background: It is commonly believed that there exists a relationship between the outcome of thyrotropin-releasing hormone (TRH) test, the combined dexamethasone\\/corticotropin-releasing hormone (DEX\\/CRH) test and stressful life events (SLEs) in major depressive disorder. Objective: SLEs influence the TRH and DEX\\/CRH tests in major depressive disorder when administered at the time of admission and improvement. Methods: The TRH and DEX\\/CRH tests
Takatoshi Hikichi; Jotaro Akiyoshi; Shugo Ichioka; Yoshihiro Tanaka; Jusen Tsuru; Shinjirou Goto; Hirotaka Matsushita; Hiroaki Hanada; Koichi Isogawa; Haruo Nagayama
To examine the effects of bilateral cervical sympathectomy on the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating\\u000a hormone (TSH), growth hormone (GH), and prolactin (PRL), 18 male rats were divided into three groups: control (Cont), sham\\u000a operation (Sham), and bilateral cervical sympathectomy (Symp). All rats were kept under a normal circadian rhythm for 2 weeks.\\u000a Subsequently, blood was collected and plasma
Hiroshi Iwama; Mamoru Adachi; Choichiro Tase; Yoichi Akama
Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea. PMID:24741461
Choi, Hong Seok; Kim, Min Joo; Moon, Chae Ho; Yoon, Jong Ho; Ku, Ha Ra; Kang, Geon Wook; Na, Im Il; Lee, Seung-Sook; Lee, Byung-Chul; Park, Young Joo; Kim, Hong Il; Ku, Yun Hyi
A 47-year-old man presented to our hospital after suffering transient loss of consciousness and falling to the floor. On admission, his Glasgow Coma Scale score was 11 (E3V3M5), and he exhibited restlessness. Blood examination revealed hyperthyroidism. Computed tomography showed slight traumatic subarachnoid hemorrhage. He developed fever and tachycardia, and was diagnosed with thyroid crisis. Magnetic resonance imaging showed a brain contusion in the right frontal lobe, and encephalopathy signs in the right frontal and insular cortex. Immunocytochemical examinations suggested Hashimoto's disease, and hormone examinations revealed plasma levels were undetectably low of adrenocorticotropic hormone (ACTH) and low of cortisol. Pituitary stimulation tests showed inadequate plasma ACTH and cortisol response, consistent with isolated ACTH deficiency (IAD). The final diagnosis was IAD associated with Hashimoto's disease. Hydrocortisone replacement therapy was continued, and the patient was nearly free from neurological deficits after 18 months. The neuroimaging abnormalities gradually improved with time. PMID:22278027
Tanei, Takafumi; Eguchi, Youko; Yamamoto, Yuka; Hirano, Masaki; Takebayashi, Shigenori; Nakahara, Norimoto
The objectives of this study were first to show adrenocortical response to a long-acting adrenocorticotropic hormone preparation (tetracosactide acetate zinc suspension) (ACTH-Z) and its effect on adrenocortical function in beef cows (Experiment 1) and second to apply the ACTH-Z challenge in dairy cows based on cortisol concentrations in milk collected at routine milking (Experiment 2). In Experiment 1, four beef cows in luteal phase were challenged with ACTH-Z, and plasma cortisol concentrations were determined for 48 h after the injection at 30-min to 2-h intervals. A rapid ACTH test was conducted 3 days before and 2 h after the completion of ACTH-Z injection for 48 h to investigate the effect on adrenocortical function. Plasma cortisol concentrations increased significantly 30 min after ACTH-Z injection (p < 0.001), and the high cortisol levels were maintained for approximately 10 h after the injection. In Experiment 2, eight dairy cows were subjected to ACTH-Z challenge 1-2 weeks and 4-5 weeks post-partum. Blood and milk samples were taken at morning and afternoon milking. All the cows showed a significant increase in cortisol concentrations in plasma as well as in skim milk 8 h after ACTH-Z injection 1-2 weeks and 4-5 weeks post-partum (p < 0.001). There was a significant correlation between plasma and skim milk cortisol concentrations 8 h after ACTH-Z challenge (r = 0.74, p < 0.001). The results obtained in this study suggest that elevated levels of plasma cortisol are maintained for approximately 10 h after ACTH-Z treatment without adverse effect on adrenocortical function and a long-acting ACTH-Z challenge based on cortisol concentrations in milk, which were collected at the morning and the afternoon milking, can be a useful tool to monitor adrenocortical function in cows. PMID:20626680
Thinh, N C; Yoshida, C; Long, S T; Yusuf, M; Nakao, T
Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.
Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others] [Univ. of Iowa College of Medicine, Iowa City, IA (United States); and others
Objective: It was the aim of this study to describe a patient with isolated adrenocorticotropic hormone deficiency presenting with a variety of involuntary movements who developed an adrenal crisis due to transient thyroiditis. Clinical Presentation and Intervention: A 61-year-old man was hospitalized with a variety of involuntary movements that were suspected manifestations of metabolic encephalopathy. After admission, his general status
Tetsuya Hiraiwa; Daisuke Furutama; Sadaki Sakane; Mitsuru Ito; Akihisa Imagawa; Fumiharu Kimura; Toshiaki Hanafusa
Background: The treatment of advanced medullary thyroid carcinoma (MTC) has evolved significantly over the past decade. The discovery of genetic abnormalities in MTC has led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and Ectopic ACTH (adrenocorticotropic hormone) Syndrome in whom treatment with sorafenib resulted in complete resolution of hypercortisolism. Summary: A 45-year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of Ectopic ACTH Syndrome. Treatment with sorafenib 400?mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question of whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion. Conclusions: This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action, or secretion. PMID:24499195
Barroso-Sousa, Romualdo; Lerario, Antonio Marcondes; Evangelista, Joao; Papadia, Carla; Lourenço, Delmar M; Lin, Chin Shien; Kulcsar, Marco Antonio; Fragoso, Maria Candida; Hoff, Ana O
We present a case of a 60-year-old woman who initially presented with pneumonia and abdominal pain and was diagnosed with ectopic adrenocorticotropic hormone (ACTH) syndrome secondary to small cell lung cancer. We review published literature and summarize the typical challenges in the diagnosis and treatment of ectopic ACTH syndrome. Recent research has shed new light on the mechanism of ectopic ACTH production and provided a potential new target for treatment.
Aitelli, Cristi; Dobson, Robin W.; Konduri, Kartik
The syndrome of opsoclonus and myoclonus may be the first presenting symptom of neuroblastoma. The disorder is often controlled by treatment with adrenocorticotropic hormone (ACTH). A child with this disorder and treated with ACTH gel had abnormal uptake of /sup 67/Ga in both adrenal glands during studies to attempt to detect an occult neuroblastoma. Repeat /sup 67/Ga scans proved to be normal once the ACTH was discontinued and the patient was treated with prednisone. It is concluded that ACTH stimulation of normal adrenal tissue was responsible for these abnormal findings.
Gumbinas, M.; Gratz, E.S.; Johnston, G.S.; Schwartz, A.D.
We report a 22-year-old woman who presented with asthenia, weight loss and hypotension in which extensive pituitary and adrenal investigations were diagnostic of isolated adrenocorticotropic hormone deficiency (IAD) of pituitary origin. Magnetic resonance imaging of the hypothalamus and pituitary showed a normal-sized pituitary, with no mass lesion. The diagnosis of IAD probably secondary to lymphocytic hypophysitis (LYH) was made. IAD is able to be the way of presentation of LYH, although the disease could or could not turn into a panhypopituitarism. Prompt recognition of this potentially fatal condition is important because of the availability of effective treatment. Indeed, regular endocrine and imaging follow up is important for patients with IAD and normal initial pituitary imaging results to detect early new-onset pituitary hormones deficiencies or imaging abnormalities. PMID:24251125
Kacem, Faten Hadj; Charfi, Nadia; Mnif, Mouna Feki; Kamoun, Mahdi; Akid, Faouzi; Mnif, Fatma; Naceur, Basma Ben; Rekik, Nabila; Mnif, Zainab; Abid, Mohamed
Background Adrenocorticotropic hormone-producing extraadrenal paragangliomas are extremely rare. We present a case of severe hypercortisolemia due to ectopic adrenocorticotropic hormone secretion by a nasal paraganglioma. Case presentation A 70-year-old Caucasian woman was emergently admitted to our department with supraventricular tachycardia, oedema of face and extremities and hypertensive crisis. Initial laboratory evaluation revealed severe hypokalemia and hyperglycemia without ketoacidosis, although no diabetes mellitus was previously known. Computed tomography revealed a large tumor obliterating the left paranasal sinus and a left-sided adrenal mass. After cardiovascular stabilisation, a thorough hormonal assessment was performed revealing marked adrenocorticotropic hormone-dependent hypercortisolism. Due to the presence of a cardiac pacemaker magnetic resonance imaging of the hypophysis was not possible. [68Ga-DOTA]-TATE-Positron-Emission-Tomography was performed, showing somatostatin-receptor expression of the paranasal lesion but not of the adrenal lesion or the hypophysis. The paranasal tumor was resected and found to be an adrenocorticotropic hormone-producing paraganglioma of low-proliferative rate. Postoperatively the patient became normokaliaemic, normoglycemic and normotensive without further need for medication. Genetic testing showed no mutation of the succinatdehydrogenase subunit B- and D genes, thus excluding hereditary paragangliosis. Conclusion Detection of the adrenocorticotropic hormone source in Cushing’s syndrome can prove extremely challenging, especially when commonly used imaging modalities are unavailable or inconclusive. The present case was further complicated by the simultaneous detection of two tumorous lesions of initially unclear biochemical behaviour. In such cases, novel diagnostic tools - such as somatostatin-receptor imaging - can prove useful in localising hormonally active neuroendocrine tissue. The clinical aspects of the case are discussed and relevant literature is reviewed.
Development of a mature adrenocortical phenotype is a critical event in the transition of mammals from fetal to postnatal life. We previously reported that the functional maturation of the adrenal glands of newborn rats is accelerated by adrenocorticotropic hormone (ACTH). We report here that chronic exposure of neonatal\\/juvenile rat pups to ACTH in vivo results in significant changes in expression
Julie J. Lee; Eric P. Widmaier
Data from spaceflight and bed rest studies are briefly described and the difficulties in interpreting these results are discussed. Growth hormone, prolactin, adrenocorticotropic hormone, cortisol, insulin, aldosterone, and other hormones are addressed.
Grindeland, R. E.
Relapses in multiple sclerosis (MS) are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the hypothalamic-pituitary-adrenal axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH) gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides [ACTH and ?-, ?-, ?-melanocyte-stimulating hormones (MSH)] and their receptors (Melanocortin receptors, MCRs) exert multiple actions, including modulation of inflammatory and immune mediator production. MCRs are widely distributed within the central nervous system and in peripheral tissues including immune cells (e.g., macrophages). This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.
Ross, Amy Perrin; Ben-Zacharia, Aliza; Harris, Colleen; Smrtka, Jennifer
The effects of chronic exposure to adrenocorticotropic hormone (ACTH) or the synthetic glucocorticoid dexamethasone (DEX) on the expression of genes involved in cortisol synthesis were examined using quantitative RT-PCR and immunohistochemistry. Juvenile Chinook salmon were treated with either ACTH via micro-osmotic pumps or with DEX via a lipid-based sustained release vehicle. Plasma cortisol levels were significantly elevated in ACTH-treated fish after 1 day, with a significant reduction in this effect with increasing treatment duration. ACTH also appeared to cause progressive hyperplasia of interrenal cells. Steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc) transcripts but not 3?-hydroxysteroid dehydrogenase-isomerase (3?-HSD) or cytochrome P450 11?-hydroxylase (P45011?) transcripts in head kidneys significantly increased after 5 days of ACTH treatment. Significant linear relationships between plasma cortisol levels and transcript levels were identified at day 1 and day 5 for StAR, and day 5 for P450scc. Increased immunoreactivity for P450scc was observed in interrenal cells of ACTH-treated fish after 5 and 10 days. No effect of ACTH on 3?-HSD immunoreactivity was apparent at any time point. P45011? immunoreactivity was more intense after 5 days treatment with ACTH. DEX significantly reduced resting plasma cortisol levels and induced interrenal cell atrophy. Although no significant effect of treatment with DEX was found for any transcript, immunoreactivity for P450scc and P45011? appeared to be reduced. These results indicate that StAR and P450scc are subject to transcriptional regulation by chronic changes in ACTH levels. PMID:21906597
McQuillan, Henry J; Kusakabe, Makoto; Young, Graham
Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and ?-lipotropin in corticotropes of the anterior lobe, and to ?-melanocyte-stimulating hormone (?-MSH) and ?-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence ?-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in ?-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by ?-methyl-p-tyrosine (?MpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma ?-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both ?MpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons.
Olah, Mark; Feher, Palma; Ihm, Zsofia; Bacskay, Ildiko; Kiss, Timea; Freeman, Marc E.; Nagy, Gyorgy M.; Vecsernyes, Miklos
We describe the case of a 2-year-old girl with opsoclonus-myoclonus syndrome treated with chronic adrenocorticotropic hormone (ACTH) in which a metaiodobenzylguanidine scan showed abnormal radiotracer uptake in the left adrenal gland region, interpreted as the site of an occult neuroblastoma. As this finding was not corroborated by previous or subsequent metaiodobenzylguanidine scans or by computed tomography (CT) or magnetic resonance
Cynthia K. McGarvey; Kimberly Applegate; Nadine Deanie Lee; Deborah K. Sokol
Adrenal vein sampling (AVS) is fundamental for subtype diagnosis in patients with primary aldosteronism. AVS protocols vary between centers, especially for diagnostic indices and for use of adrenocorticotropic hormone (ACTH) stimulation. We investigated the role of both continuous ACTH infusion and bolus on the performance and interpretation of AVS in a sample of 76 patients with confirmed primary aldosteronism. In 36 primary aldosteronism patients, AVS was performed both under basal conditions and after continuous ACTH infusion, and in 40 primary aldosteronism patients, AVS was performed both under basal conditions and after ACTH IV bolus. Both ACTH protocols determined an increase in the rate of successful cannulation of the adrenal veins. Both ACTH infusion and bolus determined a significant increase in selectivity index for the right adrenal vein and ACTH bolus for the left adrenal vein. Lateralization index was not significantly different after continuous ACTH infusion and IV bolus. In 88% and 78% of the patients, the diagnosis obtained was the same before and after ACTH infusion and IV bolus, respectively. However, the reproducibility of the diagnosis was reduced using less stringent criteria for successful cannulation of the adrenal veins. This study shows that ACTH use during AVS may be of help for centers with lower success rates, because a successful adrenal cannulation is more easily obtained with this protocol; moreover, this technique performs at least as well as the unstimulated strategy and in some cases may be even better. Stringent criteria for cannulation should be used to have a high consistency of the diagnosis. PMID:22331382
Monticone, Silvia; Satoh, Fumitoshi; Giacchetti, Gilberta; Viola, Andrea; Morimoto, Ryo; Kudo, Masataka; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Turchi, Federica; Paci, Enrico; Veglio, Franco; Boscaro, Marco; Rainey, William; Ito, Sadayoshi; Mulatero, Paolo
Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID:19641299
Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós
Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans
Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig.
Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G. [Institut Gustave-Roussy, Villejuif (France); Cossett, J.M.; Magdelenat, H. [Institut Curie, Paris (France)
Classically, upon hypothalamic stimulation, adrenocorticotropic hormone (ACTH) is released from the pituitary and acts on melanocortin 2 receptors (MC2R) in the adrenal cortex, stimulating glucocorticoid synthesis and release. Our earlier studies suggested that ACTH might have a direct effect on sympathetic ganglia. To analyze further the involvement of ACTH in regulation of gene expression of norepinephrine (NE) biosynthetic enzymes, we
L. I. Serova; V. Gueorguiev; S.-Y. Cheng; E. L. Sabban
The human adrenocorticotropic hormone receptor (ACTHR) was recently cloned and shown to belong to the superfamily of membrane receptors that couple to guanine nucleotide-binding proteins and adenylyl cyclase. A genetically heterogeneous (including both X-linked and autosomally recessive forms) congenital syndrome of general hereditary adrenal unresponsiveness to ACTH has been documented in several kindreds. This inherited defect affects one of the
N. C. Vamvakopoulos; G. P. Chrousos; K. Rojas; J. Overhauser; A. S. Durkin; W. C. Nierman
INTRODUCTION We describe a previously healthy 40-year-old woman with Cushing’s syndrome caused by adrenocorticotropic hormone (ACTH) secretion from metastatic carcinoid. CASE REPORT Over a 2-year period, the patient had multiple hospitalizations for uncontrolled hypertension, hyperglycemia, and hypokalemia. She had transient flushing, rashes, and a rapid weight gain. In addition, she developed anasarca and had a nontraumatic hip fracture 1 month before presentation. Subsequently, a hypertensive crisis resulted in admission to the intensive care unit and fine-needle aspiration of a liver lesion. DISCUSSION A diagnosis of metastatic carcinoid was established. She was transferred to our hospital for further evaluation and management. On arrival, she had the signs of Cushing’s syndrome. Despite extensive evaluation, her primary carcinoid tumor was not localized. She was treated successfully with bilateral adrenalectomy and octreotide. CONCLUSION This case illustrates how early recognition of the signs and symptoms of excess ACTH is important for prompt and appropriate treatment.
Coe, Susan G.; Fox, Thomas P.
Background Stress-induced disruption of hormonal balance in animals and humans has a detrimental effect on wound healing. The Problem After the injury, keratinocytes migrate over the wound bed to repair a wound. However, their nonmigratory phenotype plays a role in pathogenesis of chronic wounds. Despite many therapeutic approaches, there is a dearth of treatments targeting the molecular mechanisms mediated by stress that prevent epithelization. Basic/Clinical Science Advances Recent studies show that epidermal keratinocytes synthesize stress hormones. During acute wound healing, cortisol synthesis in the epidermis is tightly controlled. Further, a key intermediate molecule in the cholesterol synthesis pathway, farnesyl pyrophosphate (FPP), can bind glucocorticoid receptor (GR) and activate GR. Additionally, keratinocytes express beta-2-adrenergic-receptor (?2AR), a receptor for the stress hormone epinephrine. Importantly, migratory rates of keratinocytes are reduced by cortisol, FPP, epinephrine, and other ?2AR agonists, thus indicating their role in the inhibition of epithelization. Topical inhibition of local glucocorticoid and FPP synthesis, as well as treatment with ?2AR antagonists promotes wound epithelization. Clinical Care Relevance Modulation of local stress hormone production may represent an important therapeutic target for wound healing disorders. Topical administration of inhibitors of cortisol synthesis, statins, ?2AR antagonists, and systemic beta-blockers can decrease cortisol synthesis, FPP, and epinephrine levels, respectively, thus restoring keratinocyte migration capacity. These treatment modalities could represent a novel therapeutic approach for wound healing disorders. Conclusion Attenuation of the local stress-induced hormonal imbalance in epidermis may advance therapeutic modalities, thereby leading to enhanced epithelization and improved wound healing.
Stojadinovic, Olivera; Gordon, Katherine A.; Lebrun, Elizabeth; Tomic-Canic, Marjana
Context: Prevalence of adrenal insufficiency (AI) is not uncommon in HIV infected population. However, AI is rarely diagnosed in clinical practice because many patients have non-specific symptoms and signs. Critical illness in such patients further complicates the evaluation of adrenal function. A 1?gm ACTH test can be used for diagnosis, since it results in more physiological levels of ACTH. A serum cortisol of <18 ?g/dL, 30 or 60-minutes after ACTH test has been accepted as indicative of AI, but many experts advocate the normal cortisol response should exceed 25 ?g/dL, in critically ill patients. Aim: To determine the prevalence of AI in critically ill AIDS patients, by using 1 ?g ACTH test and also, to compare the diagnostic criteria for adrenal insufficiency between cortisol response of <18 ?g/dL and <25 ?g/dL. Settings and Design: This prospective study was done in the Department of Medicine. Materials and Methods: After taking blood for basal plasma cortisol from AIDS affected fifty adult men and women aged over 18 yrs, 1 ?g ACTH was given intravenously, and blood samples were again collected at 30 and 60 minutes for plasma cortisol estimation. Statistical analysis: It was done by Mann-Whitney test. Results: Prevalence of AI was 74% (37 patients) and 92% (46 patients), when the peak stimulated cortisol level of <18 ?g/dL and <25 ?g/dL, respectively, was used. Conclusion: AI is more prevalent in critically ill AIDS patients. Hence, this test can be performed for early intervention and better management.
Shashidhar, P. K.; Shashikala, G. V.
A method is described for the measurement of cortisol or corticotropin-releasing hormone (CRH) from the brain, within, or in the dialysate of, a microdialysis probe using an antibody-linked assay. Polyclonal antibodies for either cortisol or CRH provide a specificity of measurement. These antibodies are affixed on a platinum electrode within the probe. Determination of bound cortisol or CRH is performed
C. J Cook
The dopamine reuptake inhibitor bupropion and dopamine D2/3 receptor agonist pramipexole have been clinically proven to improve both depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of the dopamine nerve system in this effect. Bupropion and pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. We previously demonstrated that the chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation and neurogenesis. In this study, we used the mitotic marker 5-bromo-2'-deoxyridine to investigate the effects of bupropion and pramipexole on cell proliferation in the subgranular zone of the hippocampal dentate gyrus following chronic treatment with ACTH. The ACTH treatment for 14?d decreased adult hippocampal cell proliferation. The chronic administration of bupropion for 14?d blocked the loss of cell proliferation resulting from the chronic treatment with ACTH, whereas pramipexole did not. The administration of bupropion may have treatment-resistant antidepressive properties, which may be partly attributed to the normalization of hippocampal cell proliferation. PMID:24492730
Onoue, Yuka; Kuwatsuka, Keiko; Miyazaki, Ikuko; Asanuma, Masato; Kitamura, Yoshihisa; Sendo, Toshiaki
Objective:To determine cortisol and adrenocorticotropic hormone (ACTH) responses to critical illness in term and late preterm newborns and examine the relationship of these values to measures of clinical illness, including markers of cardiovascular dysfunction.Study Design:In this prospective observational study, we measured ACTH, baseline cortisol and ACTH-stimulated cortisol concentrations in mechanically ventilated infants ?34 weeks gestational age and <5 postnatal days.
E F Fernandez; R Montman; K L Watterberg
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
J. R. Metz; E. J. W. Geven; E. H. van den Burg; G. Flik
OBJECTIVES.Fasting tests are used to identify the cause of hypoglycemia in children. The purposes of this study were to (1) determine whether growth hormone and cortisol levels obtained at the time of hypoglycemia in such tests can identify children with growth hormone and\\/or cortisol deficiency and (2) identify potential clinical factors that influence growth hormone and cortisol responses to hypoglycemia.
Andrea Kelly; Randy Tang; Susan Becker; Charles A. Stanley
West syndrome (WS), an intractable epileptic encephalopathy of infancy, is refractory to many antiepileptic drugs; however, adrenocorticotropic hormone (ACTH) is an effective treatment for WS. The mechanism behind the efficacy of ACTH is mediated by biochemical processes that remain unknown. We examined the effects of ACTH therapy with tetracosactide (TCS), a synthetic ACTH analogue, on brain metabolism in patients with WS, using (1)H magnetic resonance spectroscopy ((1)H-MRS). In six patients with cryptogenic WS, we performed single-voxel (1)H-MRS at the occipital lobe cortex. Measurements were taken prior to TCS treatment, a few days after therapy, and several months after therapy. Data were also compared with subjects having only mild psychomotor delays. The metabolites measured were glutamine plus glutamate (Glx), N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI); each was expressed as a ratio with creatine plus phosphocreatine (total creatine: tCr). The Glx/tCr ratio was significantly reduced after the TCS treatment. The NAA/tCr ratio was also significantly reduced after the treatment compared with the control group, although the change in NAA signal was heterogeneous among patients, correlating with respective outcomes. The Cho/tCr and mI/tCr ratios were not affected by TCS treatment. The reduction in Glx suggests a decrease in the glutamate-glutamine cycle, which plays a pivotal role in synthesizing neurotransmitters such as glutamate and GABA. TCS-induced Glx reduction may induce changes in synaptic signal transduction, thereby accounting for the effect of TCS on WS. The change in NAA indicates altered neuronal activity, which may be correlated with outcome in WS patients. PMID:24705707
Munakata, Mitsutoshi; Togashi, Noriko; Sakamoto, Osamu; Haginoya, Kazuhiro; Kobayashi, Yasuko; Onuma, Akira; Iinuma, Kazuie; Kure, Shigeo
The serotonin receptors involved in the secretion of adrenocorticotropin hormone (ACTH) were investigated in conscious adult male rats. Administration of serotonin (5-HT), 5-hydroxytryptophan (5-HTP) in combination with the serotonin reuptake inhibitor fluoxetine (Flx), or of the 5-HT agonists 8-OH-DPAT (5-HT1A), 5-carboxamido-tryptamine (5-HT1A+1B+5A+7), RU 24969 (5-HT1B+1A), DOI (5-HT2A+2c), S-alpha-methyl-5-HT (5-HT2A+2B+2c), MK212 (5-HT2B+2c), or methyl-chlorophenyl-piperazine (5-HT2A+2c) dose-dependently stimulated ACTH secretion. The 5-HT3 agonist 2-methyl-5-HT had no effect. Administration of a 5-HT1 agonist in combination with any of the 5-HT2 agonists DOI, S-alpha-methyl-5-HT or MK212 had an additive effect on the plasma concentration of ACTH. The ACTH stimulating effect of each of the 5-HT agonists was inhibited by pretreatment with antagonists with corresponding 5-HT receptor affinity. The ACTH response to 5-HT or 5-HTP/Flx was inhibited by injection with the 5-HT1A+2A+2c+5A+7 antagonist methysergide, the 5-HT2A antagonist ketanserine and the 5-HT2C+2A antagonist LY 53857. The 5-HT1A antagonist WAY 100635 enhanced 5-HT- and 5-HTP/Flx-induced ACTH secretion, suggesting a presynaptic 5-HT1A autoreceptor effect of the drug. The 5-HT3 antagonist ondansetrone had no effect on the either of the 5-HT agonists. The 5-HT3+4 antagonist tropisetrone attenuated the effect of 5-HTP/Flx, which may suggest a stimulation of ACTH secretion via 5-HT4 receptors. It is concluded that 5-HT1A, 5-HT2A+2C, and to a lesser extent 5-HT1B receptors, but not 5-HT3 receptors are involved in the effects of serotonin agonists on ACTH secretion. Furthermore, an involvement of the 5-HT5A and the 5-HT7 receptor is possible. PMID:10223282
Jørgensen, H; Knigge, U; Kjaer, A; Warberg, J
Adrenal ornithine decarboxylase activity was stimulated in a dose-related manner after administration of ACTH or dibutyryl (6N-2?-O-dibutyryl) cyclic AMP to hypophysectomized rats. Little effect was observed for 2 h, but striking increases in enzyme activity were observed 4 h after administration of these substances. Effects of ACTH and dibutyryl cyclic AMP were not secondary to stimulation of steroidogenesis, since hydrocortisone had no effect on adrenal ornithine decarboxylase although it did stimulate activity of the enzyme in the liver and kidney. ACTH, given subcutaneously to hypophysectomized rats, induced striking increases in adrenal cyclic AMP levels within 15-30 min with a fall towards the base line in 1 h. Increases in ornithine decarboxylase activity lag several hours after this endogenous cyclic AMP peak, in contrast to the stimulatin of steroidogenesis by the nucleotide that requires only 2-3 min. After graded doses of ACTH, increases in adrenal cyclic AMP levels at 30 min were paralleled by proportional increases in adrenal ornithine decarboxylase activity 4 h after hormone treatment. Whereas maximal levels of adrenal steroidogenesis have been observed at tissue cyclic AMP levels of 6 nmol/g. ACTH is capable of inducing increases in nucleotide levels up to 200 nmol/g or more. These high tissue levels of cyclic AMP, although unneccessary for maximal steroidogenesis, appear to stimulate adrenal ornithine decarboxylase activity. Several results in addition to the time lag in the stimulation of ornithine decarboxylase activity suggest a mechanism involving accumulation of the enzyme or some factor needed for its activity rather than direct activation of the enzyme by cyclic AMP. Thus, the addition of cyclic AMP directly to the ornithine decarboxylase assay mixture in vitro was without stimulatory effect. In addition, actinomycin D or cycloheximide in doses sufficient to block adrenal RNA and protein synthesis, respectively inhibited the stimulation of ornithine decarboxylase activity by ACTH in vivo. An adrenocortical cancer was found to maintain ornithine decarboxylase activity at very high levels, but did so at much lower cyclic AMP levels than those of ACTH-stimulated adrenals. It is concluded that ACTH stimulates adrenal ornithine decarboxylase activity and that this effect may be mediated by cyclic AMP. However, cyclic AMP be mediated by appear to be a determinant of the high level of enzyme activity found in adrenocortical cancer.
Richman, R.; Dobbins, C.; Voina, S.; Underwood, L.; Mahaffee, D.; Gitelman, H. J.; Van Wyk, J.; Ney, R. L.
In 10 subjects susceptible to high altitude pulmonary oedema (HAPO) plasma cortisol and antidiuretic hormone (ADH) and urinary catecholamines were estimated both at sea level and daily during their stay at 3, 500 m (Leh). At high altitude 4 of the subjects developed HAPO, 2 got acute mountain sickness (AMS) and 4 remained unaffected. Plasma cortisol showed a sharp rise
Inder Singh; M. S. Malhotra; P. K. Khanna; R. B. Nanda; T. Purshottam; T. N. Upadhyay; U. Radhakrishnan; H. D. Brahmachari
The migratory behavior of several species of salmonids raised in hatcheries or artificial streams together with its hormonal control were studied. Masu salmon yearlings were territorial during the parr and pre-smolt stages, less aggressive during parr-smolt transformation, but aggressive after the peak of smolting. Subordinate fish had high levels of plasma cortisol, but the cortisol levels of dominants were as
ObjectiveTo examine nocturnal secretion of adrenocorticotropin, cortisol, growth hormone, and prolactin in 38 medically healthy children with prepubertal major depression compared with 28 medically and psychiatrically healthy control children.
MICHAEL D. DE BELLIS; RONALD E. DAHL; JAMES M. PEREL; BORIS BIRMAHER; MAYADAH AL-SHABBOUT; DOUGLAS E. WILLIAMSON; BEVERLY NELSON; NEAL D. RYAN
Performing quantitative, highly sensitive measurements at a single molecule level is often necessary to address specific issues related to complex molecular and biochemical systems. For that purpose, we present a technique exploiting both the flexibility of immunoassays as well as the low operating costs and high throughput rates of the fluorescence correlation spectroscopy (FCS) method. That way we have established a quantitative measurement technique providing accurate and flexibly time resolved data of single molecules. Nanomolar changes in adrenocorticotropic hormone (ACTH) levels have been detected in a short time-frame that are caused by fast feedback actions in AtT-20 anterior pituitary glands in vitro. Especially with respect to clinical diagnostic or mathematical modeling this improved FCS setup may be of high relevance in order to accurately quantify the amounts of peptide hormones—such as ACTH—as well as signaling molecules, transcription factors, etc., being involved in intra- and extracellular reaction networks.
Equine pituitary pars intermedia function can be assessed by the measurement of baseline and thyrotropin releasing hormone (TRH)-induced concentrations of adrenocorticotropic hormone (ACTH); however, these measurements may be affected by the environment. Therefore, a prospective observational study evaluated the influence of feeding, time of the day, and season on baseline and TRH-induced concentrations of ACTH in healthy horses. Baseline ACTH was measured in 50 horses before and 2 h after feeding. Six research horses were subjected to a crossover study in which 6 TRH tests were performed in 2 different seasons, March-April (MA) and July-September (JS), at 2 different times of the day, 8 AM and 8 PM, and, under 2 different conditions relative to feeding status, fasted and 2 h after feeding. Differences between fasted and fed horses were found in baseline ACTH, 17.1 ± 1.8 versus 46.1 ± 7.6 pg/mL (P = 0.003) and TRH-stimulated ACTH: 124.1 ± 21.3 versus 192.6 ± 33.1 pg/mL (P = 0.029) at 10 min, and 40.1 ± 4.9 versus 73.2 ± 13.4 pg/mL (P = 0.018) at 30 min post TRH injection. No differences were found between tests performed at different times of the day. Basal ACTH concentrations were greater in JS than in MA, 17.1 ± 1.8 versus 11.9 ± 0.6 pg/mL (P = 0.006). A seasonal influence was also found in stimulated ACTH values, which were much greater in JS 122.7 ± 36.7 versus 31.2 ± 7.4 pg/mL, at 10 min (P = 0.03) and 39.0 ± 7.2 versus 19.8 ± 3.1 pg/mL, at 30 min (P = 0.03). In addition to season, feeding is a potential confounding factor when measuring baseline or stimulated ACTH in horses. In conclusion, feeding status should be standardized for the diagnosis of equine pituitary pars intermedia dysfunction. PMID:24906932
Diez de Castro, E; Lopez, I; Cortes, B; Pineda, C; Garfia, B; Aguilera-Tejero, E
Between-individual variation of salivary progesterone (P4) and cortisol levels does not always closely reflect blood hormone concentrations. This may be partly a function of individual differences in salivary hormone excretion. We tested whether time of day at sampling and ethnicity contributed to individual variation in salivary hormones after adjusting for blood hormone levels. Forty-three Caucasian and 15 Japanese women (18–34 years) collected four sets of matched dried blood spot (DBS) and saliva specimens across a menstrual cycle (N = 232 specimen sets). Linear fixed-effects (LFE) models were used to estimate the effects of diurnal variation and ethnicity on salivary P4 and cortisol while adjusting for DBS levels. For each hormone, women with exclusively positive or negative residuals (unexplained variance) from the LFE models were categorized as high- or low-saliva-to-DBS hormone ratio (SDR; high or low salivary secretors), respectively. We found that salivary P4 (P < 0.05) was significantly higher in early morning compared to the afternoon, after controlling for DBS levels, ethnicity, and BMI. After further adjusting for this diurnal effect, significant individual variation in salivary P4 and cortisol remained: sixteen and nine women, respectively were categorized as low or high salivary secretors for both hormones (P < 0.001), suggesting systematic individual-specific variation of salivary hormonal concentration. We conclude that when saliva is used to quantify P4 or cortisol levels, time of day at sampling should be controlled. Even with this adjustment, salivary P4 and cortisol do not closely mirror between-individual variation of serum P4 and cortisol in a substantial proportion of individuals.
Konishi, Shoko; Brindle, Eleanor; Guyton, Amanda; O'Connor, Kathleen A.
The use of hormonal contraception (HC) may affect salivary cortisol levels at rest and in response to a pharmacological or stress challenge. Therefore, the current study used a secondary data analysis to investigate the effect of HC on salivary cortisol levels in response to the mu-opioid receptor antagonist naltrexone and a psychosocial stressor, and also across the diurnal curve. Two hundred and nine women (n=72 using hormonal contraception; HC+) completed a two-session stress response study that consisted of a stress day, in which they were exposed to public speaking and mental arithmetic, and a rest day, in which unstimulated cortisol levels were measured to assess the diurnal rhythm. A subset of seventy women (n=24 HC+) also completed a second study in which they were administered oral naltrexone (50mg) or placebo in a randomized, placebo-controlled, double blind fashion. Women who were HC+ had a significantly reduced salivary cortisol response to both the psychosocial stressor (p<0.001) and naltrexone (p<0.05) compared to HC- women. Additionally, HC+ women had a significantly altered morning diurnal cortisol rhythm (p<0.01), with a delayed peak and higher overall levels. The results of the current study confirm that HC attenuates salivary cortisol response to a psychosocial stressor and mu-opioid receptor antagonism, and also alters the morning diurnal cortisol curve. PMID:23672966
Roche, Daniel J O; King, Andrea C; Cohoon, Andrew J; Lovallo, William R
Cosinor analysis was used to evaluate whether pituitary and adrenal hormones exhibit circadian rhythmicity in horses. The effect of season and animal age on their respective rhythms was also determined. In addition, the usefulness of evaluating cortisol rhythmicity for the diagnosis of pituitary pars intermedia dysfunction (PPID) was assessed. Serum cortisol concentrations (P < 0.01), but not plasma ACTH or ?-melanocyte-stimulating hormone (?-MSH), showed a significant circadian periodicity in horses. An effect of season on hormone concentration was observed with plasma ACTH and ?-MSH concentration greater in the fall and cortisol concentration greater in the spring (P < 0.001). Age did not affect cortisol rhythm, but it did blunt the variation in cortisol concentration in horses, similar to what has been previously reported to occur in aged people and dogs. In addition, our results suggest that clinically and diagnostically normal, non-PPID-affected horses commonly have a loss of cortisol diurnal rhythm. Therefore, measurement of circadian rhythm is not an appropriate diagnostic test for PPID. PMID:22717182
Cordero, M; Brorsen, B W; McFarlane, D
Background. Prolactin (PRL) level is proposed to be associated with the severity of psoriasis although the previous studies reported different results. Objective. To find the association between PRL levels and severity of psoriasis before and after treatment. In addition, we aimed to find a difference in prolactin, thyroid stimulating hormone (TSH), thyroid hormones (T3 and T4), and cortisol levels between patients with psoriasis and normal controls. Methods. First, the levels of hormones were measured in 30 patients with psoriasis and 30 matched controls. The severity was assessed by psoriasis area and severity index (PASI). Then, patients were treated, and PASI was assessed every week until achieving PASI-75 response. At this time, the hormones were measured again and compared to the baseline. Results. No statistical significant difference was observed in the mean PRL, T3, T4, TSH, and cortisol levels between cases and controls. Comparing to the baseline, a significant decrease in PRL levels and a significant increase in T3 and serum cortisol levels were observed after treatment (P < 0.05), while the changes in other hormones were not significant. Conclusion. After treatment, PRL significantly decreased, and T3 and cortisol levels significantly increased. No correlation between hormone levels and improvement of PASI score existed.
Robati, Reza M.; Toossi, Parviz; Rahmati-Roodsari, Mohammad; Khalilazar, Sara; Abolhasani, Ehsan; Namazi, Nastaran; Younespour, Shima
Linear growth was studied in 20 children suffering from Still's disease on various treatment regimens, and their ability to secrete growth hormone and cortisol was investigated. Growth recovered on reducing daily corticosteroid therapy or on changing to an alternative regimen. Retardation of growth was not due to an absolute inability to secrete growth hormone. Basal plasma cortisol levels and the
R. A. Sturge; C. Beardwell; M. Hartog; D. Wright; B. M. Ansell
The hormonal responses to anaesthesia and cardiac surgery were studied in patients undergoing valve or coronary bypass surgery.\\u000a Marked increases in antidiuretic hormone levels as a result of surgical stress were seen, and were of approximately equal\\u000a magnitude in both groups. Although both groups also showed marked increases in plasma cortisol levels in response to operations,\\u000a this response appeared to
Yasu Oka; Shigeharu Wakayama; Tsutomu Oyama; Louis R. Orkin; Ronald M. Becker; M. Donald Blaufox; Robert W. M. Frater
The temporal organization of plasma melatonin. cortisol. growth hormone (GH) and prolactin secretion was examined in healthy rested controls and in patients suffering from episodic cluster headache. Eleven patients with typical cluster headache (10 men, 1 female) and 8 male controls were studied over a 24–h period: blood was collected at 2–h intervals during the day and at l-h intervals
Guy Chazot; Bruno Claustrat; Jocelyne Brun; Daniel Jordan; Geneviève Sassolas; Bernard Schott
We discuss the relationship between sleep, dreams, and memory, proposing that the content of dreams reflects aspects of memory consolidation taking place during the different stages of sleep. Although we acknowledge the likely involvement of various neuromodulators in these phenomena, we focus on the hormone cortisol, which is known to exert influence on many of the brain systems involved in
Jessica D. Payne; Lynn Nadel
In this single-blind study the effects of acute oral administration of the selective noradrenaline reuptake inhibitor reboxetine on the cortisol (COR), ACTH, growth hormone (GH) and prolactin (PRL) secretion were examined in 12 healthy male volunteers. In a randomized order, the subjects received placebo or reboxetine (4 mg) at 0800 h on two different days. After insertion of an intravenous
Cornelius Schüle; Thomas Baghai; Stefan Schmidbauer; Martin Bidlingmaier; Christian J. Strasburger; Gregor Laakmann
We discuss the relationship between sleep, dreams, and memory, proposing that the content of dreams reflects aspects of memory consolidation taking place during the different stages of sleep. Although we acknowledge the likely involvement of various neuromodulators in these phenomena, we focus on the hormone cortisol, which is known to exert…
Payne, Jessica D.; Nadel, Lynn
The bioavailability of circulating and/or endogenous hydrocortisone (cortisol) in epidermal cells is a key determinant in inflammatory disease and chronic wounds. It is not known, however, whether epidermal cells can regulate tissue cortisol and whether they are capable of producing endogenous glucocorticoids. In the present study, we show by microarray analysis that epidermal cells express mRNAs to all the major enzymes involved in the metabolic chain from cholesterol to cortisol, including cytocrome P450 chain, 11?-hydroxysteroid dehydrogenases (HSD11Bs), adrenocorticotropic hormone (ACTH) receptor (MC2R), and glucocorticoid receptor. The two enzymes mediating activation/deactivation of cortisone to cortisol, namely HSD11B1 and HSD11B2, were expressed at the protein level in cultured keratinocytes as well as human skin samples, as shown by Western blotting and immunohistochemistry, respectively. In functional assays, we show that keratinocytes are not only able to activate cortisone to cortisol in a HSD11B-dependent manner but also silencing of either HSD11B1 or HSD11B2 specifically modulates the bioavailability of the inactive glucocorticoid and the active steroid, respectively. A further key observation was that keratinocytes responded to stimulation with ACTH by a significant increase in the de novo synthesis of cortisol. Taken together, we provide evidence for a novel non-adrenal steroideal system in human keratinocytes. PMID:21344493
Cirillo, Nicola; Prime, Stephen S
The growth-independent effect of ovine growth hormone (oGH) and oGH + cortisol treatment on seawater (SW) adaptation in immature\\u000a rainbow trout, Salmo gairdneri was investigated. Fish were injected every second day with saline, 2.0 ?g oGH\\/g or 2.0 ?g oGH + 8.0 ?g cortisol\\/g for a maximum\\u000a of 8 injections in freshwater (FW). Subgroups were transferred to 28‰ SW after
Steffen S. Madsen
The human adrenocorticotropic hormone receptor (ACTHR) was recently cloned and shown to belong to the superfamily of membrane receptors that couple to guanine nucleotide-binding proteins and adenylyl cyclase. A genetically heterogeneous (including both X-linked and autosomally recessive forms) congenital syndrome of general hereditary adrenal unresponsiveness to ACTH has been documented in several kindreds. This inherited defect affects one of the steps in the cascade of events of ACTH action on glucocorticoid biosynthesis, without altering mineralocorticoid productions. Since candidate targets for pathophysiological manifestations of deficient responsiveness to ACTH include lesions of the ACTHR gene, the authors undertook to map it to a chromosomal location. They first used polymerase chain reaction (PCR) amplification of NIGMS Panel 1 DNA template to assign a 960-bp-long fragment of the human ACTHR gene to chromosome 18. Subsequently, they determined the location of the ACTHR gene within human chromosome 18 by PCR amplification of genomic DNA template from somatic cell hybrids that contain deletions of this chromosome.
Vamvakopoulos, N.C.; Chrousos, G.P. (National Institute of Child Health and Human Development, Bethesda, MD (United States)); Rojas, K.; Overhauser, J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Durkin, A.S.; Nierman, W.C. (American Type Collection, Rockville, MD (United States))
In 3 experiments, the 1st 2 of which were conducted 1 yr apart, plasma levels of testosterone (T), luteinizing hormone (LH), and cortisol were measured in 10 adult male rhesus monkeys before and shortly after coitus. Mean levels of T and LH did not increase significantly after coitus or in control (no ejaculation) tests, but cortisol levels did in both
Charles H. Phoenix; Alan F. Dixson; John A. Resko
Adrenocorticotropic hormone affects nonapoptotic cell death of undifferentiated germ cells in the fetal mouse testis: in vivo study by exo utero transplantation of corticotropic tumor cells into embryos.
Adrenocorticotropic hormone (ACTH) has been suggested to have possible roles in the fetal testes, one of the organs that express its specific receptors, melanocortin type 2 and 5 receptors (MC2R and MC5R), during the fetal period. We investigated the effect of ACTH on the cells in the testis cord of the fetal mouse testis by inducing ACTH-secreting AtT20 tumor cells in mouse fetuses. We first identified that mouse testicular germ cells at embryonic day (E) 16.5 and E18.5 spermatogonia were entirely CDH1 (E-cadherin)-positive by immunohistochemistry. We next performed AtT20-cell transplantation into the mouse fetus at E12.5, and analyzed ACTH effects on the development of fetal male mouse germ cells that express MC2R and MC5R at E16.5 and E18.5. The spermatogonia in the testis of AtT20-implanted embryos exhibited morphological changes, including pyknotic nuclei and swollen cytoplasm. In the AtT20-implanted embryos, the number of spermatogonia per unit area of the testis cord was significantly lower, but there were more pyknotic spermatogonia than in the controls. Single-stranded DNA-positive (apoptotic) and histone H3-positive (mitotic) spermatogonia were rarely observed and their numbers did not significantly differ in the two groups. Anti-Müllerian hormone (AMH)-positive Sertoli cells, another cell type that constitutes the fetal testis cord but does not express MC2R or MC5R, showed no apparent morphological changes compared with controls, nor were their numbers in the two groups significantly different between the two groups. These results suggest that ACTH, via MC2R and/or MC5R, may be involved in the nonapoptotic cell death of fetal mouse spermatogonia that is observed during the normal perinatal period. PMID:18452489
Nimura, Masayuki; Udagawa, Jun; Otani, Hiroki
The five subtypes of melanocortin receptors (MCRs) mediate the functions of ?-melanocyte-stimulating hormone (?-MSH) and adrenocorticotropic hormone (ACTH). In fish, these hormones are involved in pigment dispersion and cortisol release, respectively. ?-MSH-related peptides exhibit ACTH-like activity in certain fishes. We recently found that multiple Mcr transcripts are expressed in some cell types in the barfin flounder, which is related to
Yuki Kobayashi; Hiroaki Chiba; Kanta Mizusawa; Nobuo Suzuki; José Miguel Cerdá-Reverter; Akiyoshi Takahashi
The so-called free hormone hypothesis predicts that the biological activity of a given steroid correlates with the free protein-unbound concentration rather than with the total concentration (i.e. free plus protein-bound). Cortisol is a glucocorticoid with many diverse functions and the free hormone hypothesis seems to apply well to the observed effects of cortisol. The ovaries express glucocorticoid receptors and are
C Yding Andersen
Expression of aldosterone synthase and adrenocorticotropic hormone receptor in adrenal incidentalomas from normotensive and hypertensive patients: Distinguishing subclinical or atypical primary aldosteronism from adrenal incidentaloma.
The present study aimed to investigate the expression of aldosterone synthase (CYP11B2), adrenocorticotropic hormone receptor (ACTH-R) and their regulating transcription factors in adrenal incidentalomas (AIs) from normotensive and hypertensive patients to distinguish subclinical or atypical primary aldosteronism (PA) from AIs. Total RNA was extracted from 8 normal adrenal cortices (NAs), 46 AIs, 15 aldosterone-producing adenomas (APAs) and 6 idiopathic hyperaldosteronisms (IHAs). Real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry were performed to determine the mRNA and protein expression of CYP11B2, ACTH-R, steroidogenic factor-1 (SF1) and dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1 (DAX-1) in the different tissues. The AI hypertensive subgroup displayed increased plasma aldosterone concentration (PAC) and PAC/PRA ratio (ARR) and decreased plasma renin activity (PRA) compared to the normotensive group. CYP11B2, ACTH-R and SF1 mRNAs were signi?cantly higher in the APA group compared to the other groups, and gradually increased in AI hypertensive samples. DAX-1 mRNA was expressed faintly in PA compared with NA. In normotensive-AI samples, DAX-1 mRNA was higher compared to PA and AI hypertensive samples. Significant differences in gene expression levels in AIs were observed between probable and improbable PA patients. Immunohistochemical results were consistent with those of real-time PCR. Plasma aldosterone levels were positively correlated with CYP11B2, ACTH-R and SF1 mRNA and inversely correlated with DAX-1 mRNA. In conclusion, a significant number of hypertensive-AI patients may have subclinical forms of PA. CYP11B2, ACTH-R and their regulating transcription factors may be noteworthy in distinguishing subclinical PA from AIs. PMID:23023242
Cao, C X; Yang, X C; Gao, Y X; Zhuang, M; Wang, K P; Sun, L J; Wang, X S
Infantile spasms is an age-specific epileptic syndrome associated with poor developmental outcomes and poor response to nearly all traditional antiepileptic drugs except adrenocorticotropic hormone (ACTH). We investigated the protective mechanism of ACTH against brain damage. An infantile spasm rat model induced by N-methyl-d-aspartate (NMDA) in neonate rats was used. Pregnant rats were randomly divided into the stress-exposed and the non-stress exposed groups, and their offspring were randomly divided into ACTH-treated spasm model, untreated spasm model, and control groups. A proteomics-based approach was used to detect the proteome differences between ACTH-treated and untreated groups. Gel image analysis was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric protein identification and bioinformatics analysis. Prenatal stress exposure resulted in more severe seizures, and ACTH treatment reduced and delayed the onset of seizures. The most significantly up-regulated proteins included isoform 1 of tubulin ?-5 chain, cofilin-1 (CFL1), synaptosomal-associated protein 25, malate dehydrogenase, N(G),N(G)-dimethylarginine dimethylaminohydrolase 1, annexin A3 (ANXA3), and rho GDP-dissociation inhibitor 1 (ARHGDIA). In contrast, tubulin ?-1A chain was down-regulated. Three of the identified proteins, ARHGDIA, ANXA3, and CFL1, were validated using western blot analysis. ARHGDIA expression was assayed in the brain samples of five infantile spasm patients. These proteins are involved in the cytoskeleton, synapses, energy metabolism, vascular regulation, signal transduction, and acetylation. The mechanism underlying the effects of ACTH involves the molecular events affected by these proteins, and protein acetylation is the mechanism of action of the drug treatment.
Wang, Jing; Wang, Juan; Zhang, Ying; Yang, Guang; Zhou, Wen-Jing; Shang, Ai-Jia; Zou, Li-Ping
We report here that melanocortin peptides appear to serve as the mechanism by which weakly electric fish couple socially regulated and stress-regulated brain pathways to unique changes in the intrinsic excitability and action potential waveform of excitable membranes in peripheral cells involved in communication. Gymnotiform electric fish modulate their electric organ discharges (EODs) by reshaping the electric discharges of excitable cells in the periphery. These fish show circadian enhancement of the EOD waveform. They also enhance their EOD waveforms within minutes in response to stressors and changes in the social environment, thus altering the communication value of the signal. Changes in the EOD waveform that occur within minutes result from changes in the discharges of individual electrocytes (?EODs) mediated by the cAMP/protein kinase A (PKA) pathway acting on ion channel kinetics. What activates the cAMP/PKA pathway in electrocytes has not been identified. In vivo injections of the melanocortin peptide adrenocorticotropic hormone (ACTH) increase the amplitude and duration of the electric signal waveform of the gymnotiform Brachyhypopomus pinnicaudatus over the course of 1 h. Applied to single electrocytes in vitro, ACTH increases ?EOD amplitude and duration within minutes by differentially modulating the action potentials of the two excitable membranes of the electrocyte and changing the timing of these two spikes. Serotonin modulates the EOD in vivo but has no effect on the ?EOD in vitro. The cAMP analog 8-bromo-cAMP mimicked the effects of ACTH, whereas inhibition of PKA by protein kinase A inhibitor 14–22 amide blocked the modulatory effects of ACTH, confirming the role of the cAMP/PKA pathway in ?EOD modulation by ACTH.
Markham, Michael R.; Stoddard, Philip K.
We report here that melanocortin peptides appear to serve as the mechanism by which weakly electric fish couple socially regulated and stress-regulated brain pathways to unique changes in the intrinsic excitability and action potential waveform of excitable membranes in peripheral cells involved in communication. Gymnotiform electric fish modulate their electric organ discharges (EODs) by reshaping the electric discharges of excitable cells in the periphery. These fish show circadian enhancement of the EOD waveform. They also enhance their EOD waveforms within minutes in response to stressors and changes in the social environment, thus altering the communication value of the signal. Changes in the EOD waveform that occur within minutes result from changes in the discharges of individual electrocytes (microEODs) mediated by the cAMP/protein kinase A (PKA) pathway acting on ion channel kinetics. What activates the cAMP/PKA pathway in electrocytes has not been identified. In vivo injections of the melanocortin peptide adrenocorticotropic hormone (ACTH) increase the amplitude and duration of the electric signal waveform of the gymnotiform Brachyhypopomus pinnicaudatus over the course of 1 h. Applied to single electrocytes in vitro, ACTH increases microEOD amplitude and duration within minutes by differentially modulating the action potentials of the two excitable membranes of the electrocyte and changing the timing of these two spikes. Serotonin modulates the EOD in vivo but has no effect on the microEOD in vitro. The cAMP analog 8-bromo-cAMP mimicked the effects of ACTH, whereas inhibition of PKA by protein kinase A inhibitor 14-22 amide blocked the modulatory effects of ACTH, confirming the role of the cAMP/PKA pathway in microEOD modulation by ACTH. PMID:16177044
Markham, Michael R; Stoddard, Philip K
Objective: Morning cortisol levels are frequently used as screening tests for adrenal insufficiency in both adults and children. Reports differ on the specificity of this measurement. The present study was undertaken to determine whether sex or pubertal status affected morning cortisol values. Methods: We measured morning cortisol levels and performed low-dose adrenocorticotropic hormone stimulation test in 35 healthy male and female subjects (ages 6-34) ranging in Tanner stage (TS) from TS 1 to TS 5. Testing was initiated at 08:00 after an overnight fast. Morning serum total cortisol, free cortisol, cortisol-binding globulin, estradiol (males and females), and testosterone (males) were obtained. Results: Morning total and free cortisol levels were significantly higher in TS 5 participants than in prepubertal children. Using a morning cortisol of 248 nmol/L todefine a normal value, 19/21(90%) of healthy TS 5 subjects exhibit normal values. In contrast, 0/8 TS 1 healthy subjects exhibited a value greater than 248 nmol/L (p=0.0005). We also observed sex differences in morning cortisol levels in pubertal but not in prepubertal subjects. We observed sex differences in morning cortisol levels in TS 5 individuals. Conclusions: Morning cortisol measurements may be more useful as screening tests for adrenal function in adults than in children. TS and sex may be considered in the decision to screen for adrenal insufficiency using morning cortisol or whether to proceed directly to stimulation testing. Conflict of interest:None declared.
Tsai, Sarah L.; Seiler, Kelly J.; Jacobson, Jill
The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, ?-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p?-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis.
T?, Bechsh?ft; Sonne, C; Dietz, R; Born, EW; Muir, DCG; Letcher, RJ; Novak, MA; Henchey, E; Meyer, JS; Jenssen, BM; Villanger, GD
Cultures of enzymatically dispersed porcine anterior pituitary cells were used to examine the effects of cortisol on luteinizing hormone secretion induced by a variety of compounds which activate different intracellular signal transduction mechanisms. Cells were pre-incubated with or without cortisol (200 µg\\/ml) for 3 days, washed and then incubated for 4 h with or without cortisol in the presence or
Pi-hsueh Shirley Li
Background—Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals.Aims—To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH.Subjects—Ten IBS patients diagnosed by Rome criteria and 10 healthy controls.Methods—CRH (2 ?g\\/kg) was intravenously administered during duodenal and colonic manometry
S Fukudo; T Nomura; M Hongo
It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects. PMID:9736325
Rovenský, J; Blazícková, S; Rauová, L; Jezová, D; Koska, J; Lukác, J; Vigas, M
We investigated abnormalities of the hypothalamic–pituitary–gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated – 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients
Ali Gur; Remzi Cevik; Kemal Nas; Leyla Colpan; Serdar Sarac
Hypoglycemia is a potent stimulus for GH and cortisol secre- tion. The insulin tolerance test (ITT) is the gold standard for assessing GH and cortisol responses from the hypothalamic- pituitary-adrenal axis. The serum GH and cortisol responses to spontaneous hypoglycemia in 22 children were compared with those of 16 children undergoing an ITT for diagnostic purposes. The mean serum GH
K. Hussain; P. HINDMARSH; A. AYNSLEY-GREEN
Summary The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), -endorphin (EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in
Nicole Fellmann; Mario Bedu; Gil Boudet; Martine Mage; Marcel Sagnol; Jean-Marc Pequignot; Bruno Claustrat; Jocelyne Brun; Liliane Peyrin; Jean Coudert
Exercise of appropriate intensity is a potent stimulus for GH and cortisol secretion. Circadian and diurnal rhythms may modulate the GH and cortisol responses to exercise, but nutrition, sleep, prior exercise patterns, and body composition are potentially confounding factors. To determine the influence of the time of day on the GH and cortisol response to acute exercise, we studied 10
JILL A. KANALEY; JUDY Y. WELTMAN; KAREN S. PIEPER; ARTHUR WELTMAN; MARK L. HARTMAN
The in vitro effects of cortisol and GH on basal and stimulated lipolysis in human adipose tissue were studied using a tissue incu- bation technique. After preincubation for 3 days in control medium containing insulin, adipose tissue pieces were exposed to cortisol for 3 days. GH was added to the cortisol-containing medium during the last 24 h (day 6). Adipocytes
MALIN OTTOSSON; PETER LONNROTH; PER BJORNTORP; STAFFAN EDEN
Myostatin (MSTN) negatively regulates muscle growth in vertebrates. Salmonids produce two myostatin transcripts from separate genes. Surprisingly, quantitative analyses indicate different regulatory mechanisms for the two myostatin genes in rainbow trout. MSTN1 mRNA levels were elevated 26% following recombinant bovine growth hormone (rbGH) treatment, while MSTN2 mRNA levels were reduced 74% compared to controls. MSTN precursor protein (42kDa) levels were elevated in rbGH treated fish compared to controls. In addition, circulating cortisol levels were elevated 71% following rbGH treatment compared to controls. In treated and control fish, cortisol levels were elevated 245% at day 0 compared to subsequent days. Treated fish exhibited cortisol levels 207% higher than controls at 0.5 day, and remained at least 50% higher for 7 days following treatment. This pattern of change was positively correlated to MSTN1 mRNA levels. This is the first time a direct relationship has been reported between GH, cortisol, and myostatin. In addition, following rbGH administration, myosin protein concentrations in skeletal muscle samples increased, suggesting that GH regulates expression of the most abundant muscle protein. These results indicate the two myostatin genes are differentially regulated and may possess different functions in rainbow trout muscle, and suggests a possible interaction between GH, cortisol, and muscle growth. PMID:15242749
Biga, Peggy R; Cain, Kenneth D; Hardy, Ronald W; Schelling, Gerald T; Overturf, Kenneth; Roberts, Steven B; Goetz, Frederick W; Ott, Troy L
The circadian rhythm of serum prolactin was determined in 12 patients with seizures, and 28 age- and sex-matched healthy subjects (14 men and 14 women). Blood was also collected every 15 min for 2 h immediately after a simultaneously video\\/EEG-documented epileptic (6 patients) and psychogenic seizure (5 patients) for the determination of prolactin, thyrotropin, growth hormone, cortisol, melatonin, catecholamines and
Marie Luise Rao; Hermann Stefan; Jürgen Bauer
BackgroundWe studied serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), triiodothyronine (T3), free T3 (FT3), cortisol and growth hormone (GH) concentrations in a population of pediatric patients. The reference intervals were determined separately for females and males stratified by age groups to assess age- and sex-related differences. Our objective was to obtain reference intervals for the 7 serum analytes
Offie P. Soldin; Eve G. Hoffman; Michael A. Waring; Steven J. Soldin
b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) functions as a net reductase converting cortisone to cortisol. GH inhibits 11b- HSD1, resulting in a shift in cortisol metabolism favoring cortisone, an observation that may have significance in patients with ACTH deficiency who are unable to compensate for such changes. We have studied the effect of three doses of GH replacement (0.17, 0.33, and
A. A. Toogood; N. F. TAYLOR; S. M. SHALET; J. P. MONSON
The aim of this study was to characterize the pituitary–interrenal axis in barfin flounder, a flatfish. Adrenocorticotropic hormone (ACTH) and melanocortin 2 receptor (MC2R) have been shown to be indispensable substances in pituitary and interrenal cells for cortisol release, respectively. We previously identified ACTH in the pars distalis of the barfin flounder pituitary gland, and detected transcripts of Mc1r, Mc4r,
Yuki Kobayashi; Hiroaki Chiba; Takeshi Yamanome; Helgi B. Schiöth; Akiyoshi Takahashi
Introduction Previous studies have shown that hormonal factors such as levels of insulin, cortisol, testosterone, and insulin resistance are related with increased nephrolithiasis (NL). However, no previous study has evaluated the relationship between insulin, insulin resistance, thyroid hormones, cortisol, intact parathyroid hormone and testosterone levels with the presence of NL in a comprehensive manner. Materials and methods All patients underwent the following procedures: history taking, physical examination, biochemical analysis [including measurement of levels of insulin, thyroid hormones, cortisol, and total testosterone (for male patients only)], urine analysis, 24–hour urine collection to measure urinary protein, sodium excretion, and creatinine clearance. Insulin resistance was evaluated by the homeostasis model assessment index (HOMA–INDEX). The presence of NL was determined by ultrasonography. Results The study was composed of 136 patients. In total, 30 patients had NL. Patients with NL were more likely to be older, male, obese, and smokers. Uric acid and HOMA–INDEX were also higher in patients with NL. In the whole group, only insulin (Odds ratio:1.128, CI:1.029–1.236, P:0.01) but not other hormones, and HOMA–INDEX were related with the presence of NL. In males, none of the hormones including total testosterone were associated with NL. Conclusions Only levels of insulin, but not other hormones were associated with the presence of NL in a group of patients with suspicion of NL. More studies are needed to highlight the mechanisms regarding NL and hormone levels.
Background Recent attention has been given to subclinical hypothyroidism, defined as an elevation of TSH (4.5-10 uIU/L) with T4 and T3 levels still within the normal range. Controversy exists about the proper lower limit of TSH that defines patients in the subclinical hypothyroidism range and about if/when subclinical hypothyroidism should be treated. Additional data are needed to examine the relationship between markers of thyroid function in the subclinical hypothyroidism range, biomarkers of health and ultimately health outcomes. Objective We aimed to assess the relationship between serum TSH levels in the 0.5-10 uIU/L range and serum cortisol in a cohort of healthy young men and women without clinical evidence of hypothyroidism. Based on data in frank hypothyroidism, we hypothesized that serum TSH levels would be positively correlated with serum cortisol levels, suggesting derangement of the cortisol axis even in subclinical hypothyroidism. Methods We conducted a cross sectional study in 54 healthy, young (mean 20.98 +/? 0.37 yrs) men (19) and women (35). Lab sessions took place at 1300 hrs where blood was drawn via indwelling catheter for later assessment of basal serum TSH, free T3, free T4, and cortisol levels. Results All but 1 participant had free T3 levels within the normal reference intervals; free T4 levels for all participants were within the normal reference intervals. Linear regression modeling revealed that TSH levels in the 0.5-10 uIU/L were significantly and positively correlated with cortisol levels. This positive TSH-cortisol relationship was maintained below the accepted 4.5 uIU/L subclinical hypothyroid cutoff. Separate regression analyses conducted by systematically dropping the TSH cutoff by 0.50 uIU/L revealed that the TSH-cortisol relationship was maintained for TSH levels (uIU/L) ?4.0, ?3.5, ?3.0, and ?2.5 but not ?2.0. Linear regression modeling did not reveal a relationship between free T3 or free T4 levels and cortisol levels. Conclusions Results suggest a positive relationship between TSH and cortisol in apparently healthy young individuals. In as much as this relationship may herald a pathologic disorder, these preliminary results suggest that TSH levels > 2.0 uIU/L may be abnormal. Future research should address this hypothesis further, for instance through an intervention study.
Alcohol-mediated alterations in hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis function are two proposed mechanisms by which alcohol causes neurodevelopmental injury to the fetus. We previously reported that third trimester-equivalent only alcohol exposure in sheep results in increases in the maternal and fetal adrenocorticotropin (ACTH) and cortisol levels, and decreases in the fetal thyroid hormones T3 and T4 and maternal T3 levels. In this study, we wished to characterize the maternal HPA and HPT hormone responses to repeated binge alcohol exposure during all three trimester-equivalents of pregnancy in sheep. Pregnant ewes received intravenous infusions of alcohol at doses of 0.75, 1.25 or 1.75 g/kg over 1 hour with mean peak blood alcohol concentrations of 90, 126 or 183 mg/dl respectively on three consecutive days each week beginning on gestation day (GD) 4. Maternal blood samples were collected on GDs 6, 40, 90, and 132. Maternal plasma concentrations of ACTH and cortisol increased in response to the high alcohol dose, and the magnitude of these elevations was not different across gestation. Thyroid hormone levels were not different when comparing among treatment groups at any time point during gestation. However, there was an ontogenetic decrease in the maternal T3 concentration beginning between GDs 6 and 40 and a decrease in maternal T4 and free T4 beginning between GDs 40 and 90. The current findings suggest that: 1) maternal alcohol consumption at any time during gestation stimulates the HPA axis, 2) maternal HPA responsiveness to alcohol does not change across gestation, 3) binge alcohol exposure at these doses lasting all three trimester equivalent of human brain development does not reduce maternal thyroid hormone concentration, 4) alterations in fetal thyroid function in response to alcohol exposure do not occur as a result of diminished maternal thyroid hormone contribution, and 5) there is an ontogenetic decrease in ovine maternal thyroid hormones over gestation.
Ramadoss, Jayanth; Tress, Ursula; Chen, Wei-Jung A.; Cudd, Timothy A.
Summary Both acute and chronic stress can impair maternal behavior and increase rates of infant abuse in several species. The mechanisms inducing these effects are unknown, but experimental manipulation of circulating corticosterone levels alters maternal behavior in rats, and circulating or excreted cortisol concentrations have been found to correlate either positively or negatively with maternal behavior in humans and nonhuman primates. In this study, therefore, we experimentally tested the hypothesis that both acute and chronic treatment with exogenous glucocorticoids would alter maternal behavior in a primate, the common marmoset (Callithrix jacchus). Multiparous females, approximately 3?5 weeks postpartum, received daily injections of either cortisol (hydrocortisone sodium succinate and hydrocortisone acetate; N = 7) or vehicle (N = 7) for 8 days, and maternal behavior was characterized under baseline conditions as well as during exposure to a noise stressor. Cortisol treatment successfully elevated both morning and afternoon plasma cortisol concentrations and suppressed circulating levels of adrenocorticotropic hormone. In home-cage observations, cortisol-treated females carried their infants significantly less than control mothers, and in noise-stressor tests, several hours after the first cortisol or vehicle treatment, cortisol-treated mothers inspected their infants significantly more often than controls. Aggression towards infants was infrequent and mild, and did not differ between treatment groups. These findings provide the first experimental evidence that cortisol elevations can alter maternal behavior in primates. As these effects were limited in scope, however, they suggest that other stress-responsive hormones or neuropeptides may additionally play a role in mediating the effects of stress on maternal behavior.
Saltzman, Wendy; Abbott, David H.
Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE), cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 46 normal subjects, 28 high intestinal tone (high IT) and 18 low intestinal tone (low IT), before and after the administration of a single intramuscular dose of clonidine (2.5 ?g\\/kg). High IT subjects had lower mean values
Fuad Lechin; Bertha van der Dijs; Daniela Jakubowicz; Rheyna Cameron; Simón Villa; Ernesto Lechin; Francisco Gómez
In the sockeye salmon (Onchorynchus nerka), as well as a number of migratory salmonid species, the plasma level of cortisol, the main stress hormone in fish, increases during the spawning period, and then fish die after the spawning. The response of cultured individuals of this species to an artificial acute stress during the spawning period was investigated by measuring levels
K Kubokawa; T Watanabe; M Yoshioka; M Iwata
We previously demonstrated that repeated treatment of rats with the standardized extract of Ginkgo biloba leaves, EGb 761, and its bioactive component ginkgolide B (GKB), specifically reduces the ligand binding, and protein and messenger RNA expression of the adrenal mitochondrial peripheral benzodiazepine receptor (PBR), a key element in the regulation of cholesterol transport, resulting in decreased circulating corticosterone levels. Adrenocortical cells were isolated from rats treated with EGb 761 or GKB and cultured for 2 and 12 days. The effect of ACTH on normal and metabolically labeled cells was examined. Corticosterone levels were measured by RIA, and protein synthesis was analyzed by two-dimensional gel electrophoresis. Ex vivo treatment with EGb 761 and GKB resulted, respectively, in 50% and 80% reductions of ACTH-stimulated corticosterone production by adrenocortical cells cultured for 2 days compared with that by cells isolated from saline-treated rats. Two-dimensional gel electrophoresis analysis revealed that in cells from both control and drug-treated animals, ACTH induced the synthesis, at the same level, of a 29-kDa and pI 6.4-6.7 protein identified as the adrenal steroidogenic acute regulatory protein (StAR). In addition, treatment with EGb 761 and GKB specifically altered the synthesis of seven proteins, including inhibition of synthesis of a 17-kDa, identified as PBR. After 12 days in culture, ACTH-stimulated adrenocortical cell steroid synthesis was maintained, and it was identical among the cells isolated from animals treated with GKB or saline. Under the same conditions, the expression of PBR was recovered, whereas no effect of ACTH on the 29-kDa and 6.4-6.7 pI protein (StAR) or other protein synthesis could be seen. A comparative analysis of the effects of GKB and EGb 761 on adrenocortical steroidogenesis and protein synthesis identified, in addition to the 17-kDa PBR, target proteins of 32 kDa (pI 6.7) and 40 kDa (pI 5.7-6.0) as potential mediators of the effect of EGb 761 and GKB on ACTH-stimulated glucocorticoid synthesis. In conclusion, these results 1) validate and extend our previous in vivo findings on the effect of EGb 761 and GKB on ACTH-stimulated adrenocortical steroidogenesis, 2) demonstrate the specificity and reversibility of EGb 761 and GKB treatment, 3) question the role of the 29-kDa, 6.4-6.7 pI protein (mature StAR) as the sole mediator of ACTH-stimulated steroid production, and 4) demonstrate the obligatory role of PBR in hormone-regulated steroidogenesis. PMID:9389527
Amri, H; Drieu, K; Papadopoulos, V
Backgrounds In vitro fertilization involves high dosage gonadotropin stimulation, which apparently has some negative impact on follicular endocrine function. As chorionic gonadotropin stimulation has been shown to increase the blood-follicular permeability in animal models, this raises the question if such an effect also applies to gonadotropins in humans, possibly affecting the endocrine follicular milieu. Findings Follicular fluid and serum were collected at the time of follicular aspiration in in vitro fertilisation without (Natural cycle IVF, n?=?24) and with (conventional gonadotropin stimulated IVF, n?=?31) gonadotropin stimulation. The concentration of the extra-ovarian hormones prolactin and cortisol were analysed by immunoassays. Results Median serum prolactin and cortisol concentrations were 12.3 ng/mL and 399 nmol/L without versus 32.2 ng/mL and 623 nmol/L with gonadotropin stimulation. The corresponding concentrations in follicular fluid were 20.6 ng/mL and 445 nmol/L versus 28.8 ng/ml and 456 nmol/L for prolactin and cortisol. As a consequence, mean follicular fluid:serum ratios were significantly reduced under gonadotropin stimulation (prolactin p?=?0.0138, cortisol p?=?0.0001). As an enhanced blood-follicular permeability and transportation, induced by gonadotropin stimulation, would result in increased instead of decreased follicular fluid:serum ratios as found in this study, it can be assumed that this does not affect extra-ovarian protein and steroid hormones as illustrated by prolactin and cortisol. Conclusions The model of serum follicular fluid:serum ratio of hormones, produced outside the ovaries, did not reveal a gonadotropin induced increased blood-follicular transportation capacity. Therefore it can be assumed that the effect of gonadotropins on follicular endocrine function is not due to an increased ovarian permeability of extra-ovarian hormones.
In six cows, twice daily administration of 100 IU corticotropin for 3.5 days during the follicular phase delayed the preovulatory luteinizing hormone surge and onset of behavioral estrus. Corti- cotropin increased progesterone and decreased estradiol and basal luteinizing hormone concentrations of blood. Fol- lowing corticotropin withdrawal, a short- ened period of behavioral estrus (50% of control) was accompanied by an
D. P. Stoebel; G. P. Moberg
Glucocorticoid deficiency leads to elevated plasma vasopressin (AVP), while chronic endogenous hypercortisolism may inhibit osmotically stimulated AVP, suggesting that glucocorticoids may be feedback inhibitors of AVP secretion. We evaluated the effect of physiological increases in cortisol (65 mg/day iv) for 7 days on basal AVP and oxytocin (OT) in five conscious, male dogs. Cortisol increased from 1.3 +/- 0.1 to 5.0 +/- 0.8 micrograms/dl during infusion. Basal plasma AVP significantly decreased from 3.5 +/- 0.2 to 2.6 +/- 0.3 pg/ml during cortisol infusion. Plasma OT, osmolality, and sodium did not change while arterial pressure decreased (from 107 +/- 3 to 102 +/- 2 mmHg) on days 4 and 6. Increases in cortisol led to a physiologically significant, nonosmotic decrease in AVP. The effect was specific to AVP and independent of changes in arterial pressure. Glucocorticoid administration significantly decreased basal AVP within 24 h, which is comparable to the negative feedback control of adrenocorticotropic hormone. The inverse relationship between cortisol and AVP may account for the nonosmotic change in AVP in patients with disorders of glucocorticoid secretion. PMID:8024023
Papanek, P E; Raff, H
Forskolin (FSK; an activator of adenylyl cyclase) and cortisol synergistically increase the concentration of oxytocin receptors (OTRs) in rabbit amnion cells. The aims of this study were to characterize potential physiological regulators of OTR concentrations acting through adenylyl cyclase and to clarify the mechanisms of potentiation by cAMP and cortisol. Both isoproterenol (ISO) and parathyroid hormone-related protein (PTHrP) elevated amnion cell cAMP levels and OTR concentrations. The effects of ISO and PTHrP on OTR were potentiated by cortisol. Cortisol had no effect on the ability of ISO or PTHrP to stimulate adenylyl cyclase activity, and cAMP did not affect the number or affinity of glucocorticoid receptors in whole cells or in cytosol. Adenylyl cyclase activation, however, caused conversion of mifepristone (RU486) from a glucocorticoid antagonist to agonist. Thus, mifepristone elevated OTR receptor concentrations in the presence of FSK. In contrast, a structurally related glucocorticoid antagonist, onapristone (ZK98 299), was unaffected by cAMP. Because glucocorticoid receptors bound to mifepristone are capable of interacting with DNA, whereas onapristone-occupied receptors are not, we conclude that cAMP affects glucocoticoid receptor-DNA interactions, accounting for the synergistic effects of cAMP and cortisol on OTRs. PMID:8527507
Jeng, Y J; Hinko, A; Soloff, M S
Ectopic adrenocorticotropic hormone secretion is responsible for 12% to 17% of all cases of the Cushing syndrome. One of the most commonly described causes of ectopic adrenocorticotropic hormone secretion is small cell carcinoma of the lung. A rare cause includes a functioning neuroendocrine tumor traditionally known as carcinoids that account for 5% of all mediastinal tumors. To our knowledge, all reported cases of mediastinal carcinoids are thymic in origin and only a minority of those is functional. We present a male patient with hypertension, obstructive sleep apnea, and acid-base disorder, in whom further investigation revealed an anterior mediastinal mass and Cushing syndrome. PMID:24739692
Venkatram, Sindhaghatta; Vakde, Trupti; Badipatla, Kanthi; Niazi, Masooma; Diaz-Fuentes, Gilda
Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE) plasma levels, cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 26 high intestinal tone (high-IT) and 24 low intestinal tone (low-IT) depressed patients, before and after the intramuscular injection of clonidine (2.5 ?g\\/kg). A positive correlation was found between NE, DBP, and Hamilton Depression Rating
Fuad Lechin; Bertha van der Dijs; Daniela Jakubowicz; Rheyna E. Cameron; Simon Villa; Luis Arocha; Alex E. Lechin
The present study was designed to investigate the relations between plasma ghrelin concentrations, eating patterns, and circulating concentrations of cortisol and thyroid hormones in women with anorexia nervosa, bulimia nervosa, and binge-eating disorder. The patterns of disordered eating behavior were assessed using the Eating Attitudes Test (EAT-26) and the Bulimia Test-Revised (BULIT-R). In women with eating disorders, but not in
Alfonso Troisi; Giorgio Di Lorenzo; Ilaria Lega; Manfredi Tesauro; Aldo Bertoli; Roberto Leo; Micaela Iantorno; Chiara Pecchioli; Stefano Rizza; Mario Turriziani; Renato Lauro; Alberto Siracusano
Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of
Harold W. Koenigsberg; Martin H. Teicher; Vivian Mitropoulou; Carryl Navalta; Robert Trestman; Larry J. Siever
In order to characterize the individual diurnal plasma profiles of triiodothyronine (T3) and thyroxine (T4) in rainbow trout (Oncorhynchus mykiss), blood samples from 41 fish were taken every hour during a 24-hr period, through a catheter inserted into the dorsal aorta. The possible influences of day-night alternation, sex, and diet (feed intake, time of meals) on thyroid hormone (TH) profiles were analyzed. The existence of relations between diurnal plasma profiles of T3, T4, T3/T4 ratio, and those of the growth hormone (GH), cortisol (previously described in Gomez et al., J. Exp. Zool. 274, 171-180, 1996), and the growth rate was monitored. Average daily T3 and T4 concentrations were, respectively, 2.6 +/- 0.2 and 5.5 +/- 0.3 ng/ml (n = 41). Our study showed little or no variation in plasma T3 concentrations during one 24-hr period, while those of T4 fluctuated markedly. T4 peaks occurred from a baseline of 4.0 +/- 0.2 ng/ml at a frequency of 2.5 +/- 0.2 peaks/24 hr, with an amplitude of 3.0 +/- 0.4 ng/ml, and a duration of 4.3 +/- 0.4 hr. There was a significant difference between the average circulating T3 level during the day and that at night (2.4 +/- 0.2 vs 2.7 +/- 0.2 ng/ml). No influence of sex or food factors was observed on daily TH concentrations. TH peaks occurred irregularly and asynchronously without apparent influence of day-night alternation, sex, and diet. The growth rate was significantly correlated with the daily T3 concentration (r = 0.77), but not with T4. No significant relationships were found between daily concentrations of T3, T4, GH, and cortisol. The absence of a relationship between TH and GH concentrations suggests that, in salmonids, GH may have no observable short-term action on the conversion of T4 to T3. PMID:9208307
Gomez, J M; Boujard, T; Boeuf, G; Solari, A; Le Bail, P Y
This experiment was designed to determine the effects of sexual stimulation on plasma concentrations of oxytocin (OT), vasopressin (VP), 15-ketodihydro-PGF(2alpha) (PG-metabolite), luteinizing hormone (LH), testosterone (T), estrone sulfate (ES), and cortisol (C) in stallions. Semen samples were collected from 14 light horse stallions (Equus caballus) of proven fertility using a Missouri model artificial vagina. Blood samples were collected at 15, 12, 9, 6, and 3 min before estrous mare exposure, at erection, at ejaculation, and at 3, 6, and 9 min after ejaculation. Afterwards, blood sampling was performed every 10 min for the following 60 min. Sexual activity determined an increase in plasma concentrations of OT, VP, C, PG-metabolite, and ES and caused no changes in LH and T concentrations. The finding of a negative correlation between C and VP at erection, and between C and T before erection and at the time of erection, could be explained by a possible inhibitory role exerted by C in the mechanism of sexual arousal described for men. PMID:20022362
Veronesi, M C; Tosi, U; Villani, M; Govoni, N; Faustini, M; Kindahl, H; Madej, A; Carluccio, A
Effect of prolonged exposure to low concentrations of formaldehyde on the corticotropin releasing hormone neurons in the hypothalamus and adrenocorticotropic hormone cells in the pituitary gland in female mice.
We examine the effect on the hypothalamus-pituitary-adrenal gland (HPA) axis of prolonged exposure to low levels of formaldehyde in female C3H/He mice, using immunocytochemical and RT-PCR methods. Two groups of female mice were exposed to differing concentrations (0, 80, 400, 2000 ppb) of formaldehyde inhalation for 16 h/day, 5 days/week, for 12 weeks. The corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons in the hypothalamus were then examined, together with the adrenocorticotropin hormone (ACTH)-ir cells and ACTH mRNA in the pituitary. One group comprised sham control mice. The other group was made allergic by injection of ovalbumin (OVA) and alum prior to exposure to formaldehyde, since most sick building syndrome (SBS) sufferers are women with allergic disease. These animals were further exposed to aerosolized OVA as a booster four times during the exposure period. Our results showed a dose-dependent increase in the number of CRH-ir neurons in the non-allergy (NAG) group. A similar pattern was found in ACTH-ir cells and ACTH mRNA. The allergy (AG) model group showed an increase in basal levels of all markers of HPA activity. Moreover, the AG mice appeared to respond to the lowest concentration of formaldehyde, and all indices of HPA activity were reduced at the highest concentrations of formaldehyde. These results relate to an important clinical issue and also have implications in the broader area of HPA regulation. We conclude that our experimental system may be a suitable animal model for SBS and/or multiple chemical sensitivity (MCS). PMID:15196973
Sari, Dwi Kesuma; Kuwahara, Sachi; Tsukamoto, Yasuhiro; Hori, Hajime; Kunugita, Naoki; Arashidani, Keiichi; Fujimaki, Hidekazu; Sasaki, Fumihiko
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. PMID:15890786
Metz, Juriaan R; Geven, Edwin J W; van den Burg, Erwin H; Flik, Gert
Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses. PMID:15326569
Dall'Asta, C; Ballarè, E; Mantovani, G; Ambrosi, B; Spada, A; Barbetta, L; Colombo, P; Travaglini, P; Loli, P; Beck-Peccoz, P
The objective of this study was to evaluate the effects of nocturnal sleep, partial night sleep deprivation, and sleep stages on circulating concentrations of interleukin-6 (IL-6) in relation to the secretory pro- files of GH, cortisol, and melatonin. In 31 healthy male volunteers, blood samples were obtained every 30 min during 2 nights: uninter- rupted, baseline sleep and partial sleep
LAURA REDWINE; RICHARD L. HAUGER; J. CHRISTIAN GILLIN; MICHAEL IRWIN
Main Outcome Measures: RER, GH, cortisol, oxygen consumption, heart rate, tympanic temperature, and lactate were obtained during both protocols at matched time intervals and analyzed by repeated measures ANOVA. Results: During baseline, there were no differences detected be- tween lean and obese groups for any of the measured variables. In contrast, during exercise, peak GH levels were blunted (P 0.05)
Tina Wong; Vicki Harber
The capacity of cortisol, ovine growth hormone (oGH), recombinant bovine insulin-like growth factor I (rbIGF-I) and 3,3',5-triiodo-l-thyronine (T3) to increase hypoosmoregulatory capacity in the euryhaline teleost Fundulus heteroclitus was examined. Fish acclimated to brackish water (BW, 10 ppt salinity) were injected with a single dose of hormone suspended in oil and transferred to seawater (SW, 35 ppt salinity) 10 days post-injection. Fish
J. M. Mancera; S. D. McCormick
... (a) Identification. A cortisol (hydrocortisone and hydroxycorticosterone...device intended to measure the cortisol hormones secreted by the adrenal gland in plasma and urine. Measurements of cortisol are used in the diagnosis...
... (a) Identification. A cortisol (hydrocortisone and hydroxycorticosterone...device intended to measure the cortisol hormones secreted by the adrenal gland in plasma and urine. Measurements of cortisol are used in the diagnosis...
The diurnal variation of plasma beta endorphin was studied in ten schizophrenics, and in age\\/sex matched control subjects. In the controls beta endorphin was high in the morning (21.0±3.5 pmol\\/l) and decreased towards evening. In the schizophrenic group the beta endorphin fluctuated randomly, ranging within 9–40 pmol\\/l throughout the day. Plasma cortisol showed a normal diurnal pattern in both groups.
I. Gil-Ad; Z. Dickerman; S. Amdursky; Z. Laron
Sixteen light horse mares were fed diets of bermudagrass hay and a cordcottonseed hull- based supplement formulated to contain either 100% (control) or 50% (restricted) of the protein and(or) energy requirements for maintenance in a 2 x 2 factorial arrangement of treatments. Plasma IGF-I, prolactin, cortisol, triiodothyronine, and thyroxine were monitored for 33 d. On the 27th d, frequent blood
L. S. Sticker; D. L. Thompson; J. M. Fernandez; L. D. Bunting; C. L. DePew
Blockade of the renin-angiotensin-aldosterone system (RAAS) is an established method to lower blood pressure in patients with hypertension. Aldosterone, the end product of the RAAS cascade, acts by increasing salt reabsorption in the kidney and catecholamine release from the adrenal medulla. Currently available aldosterone inhibitors have the disadvantage of increasing circulating aldosterone and thus may lead to aldosterone breakthrough. Aldosterone synthase inhibition (ASI) is a novel approach to suppressing the RAAS. Due to homology between the enzymes responsible for aldosterone synthesis (CYP11B2) and cortisol synthesis (CYP11B1), the blockade of aldosterone synthesis may also suppress cortisol release. The authors evaluated the effect of the novel ASI LCI699 on the cortisol response to adrenocorticotropic hormone (ACTH) stimulation in patients with hypertension in order to find the maximally tolerated dose (MTD) in this patient population. Among the 63 patients evaluated, there was a dose- and time-dependent effect of LCI699 on both aldosterone and ACTH-stimulated cortisol. Based on exposure-response analysis, the MTD was estimated to be 1.30 mg once daily with a 90% prediction interval of 0.88 mg once daily to 1.81 mg once daily. No patients required intervention for adrenal insufficiency. LCI699 was well tolerated with no serious adverse events. PMID:22947355
Andersen, Karl; Hartman, Daniel; Peppard, Thomas; Hermann, David; Van Ess, Peter; Lefkowitz, Martin; Trapani, Angelo
OBJECTIVE The present study examined associations between psychological reactivity and hormonal responses to a standardized laboratory stressor (the Trier Social Stress Test [TSST]) in postmenopausal women. METHODS Forty postmenopausal women ages 50–74 completed anxiety and mood assessments prior to and following the TSST. Blood samples were drawn across multiple time points for assessment of cortisol, adrenocorticotropic hormone (ACTH), and DHEA. RESULTS As expected, significant increases in anxiety and negative affect and decreases in positive affect were observed from pre- to post-TSST; however, the magnitude of change in anxiety and mood varied considerably across individuals. Analyses indicated that greater increases in anxiety and negative affect from pre- to post-TSST were associated with higher levels of cortisol, ACTH, and DHEA, controlling for race, age, body mass index, and smoking status. Changes in positive affect were not associated with cortisol, ACTH, or DHEA. CONCLUSIONS These findings suggest that enhanced reactivity to stress is associated with higher hormone levels among postmenopausal women, which could have potential implications for health.
Fang, Carolyn Y.; Egleston, Brian L.; Manzur, Angelica M.; Townsend, Raymond R.; Stanczyk, Frank Z.; Spiegel, David; Dorgan, Joanne F.
Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that ?-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.
Wong, Ma-Li; Kling, Mitchel A.; Munson, Peter J.; Listwak, Samuel; Licinio, Julio; Prolo, Paolo; Karp, Brian; McCutcheon, Ian E.; Geracioti, Thomas D.; DeBellis, Michael D.; Rice, Kenner C.; Goldstein, David S.; Veldhuis, Johannes D.; Chrousos, George P.; Oldfield, Edward H.; McCann, Samuel M.; Gold, Philip W.
The five subtypes of melanocortin receptors (MCRs) mediate the functions of ?-melanocyte-stimulating hormone (?-MSH) and adrenocorticotropic hormone (ACTH). In fish, these hormones are involved in pigment dispersion and cortisol release, respectively. ?-MSH-related peptides exhibit ACTH-like activity in certain fishes. We recently found that multiple Mcr transcripts are expressed in some cell types in the barfin flounder, which is related to regulation of ?-MSH activities. Similar results were also observed for the cortisol-releasing activity of ?-MSH-related peptides in the head kidney. The present study was undertaken to assess relationship between the expression of multiply expressed Mcrs and ?-MSH activities using goldfish. We also determined if ?-MSH-related peptides exhibit ACTH-like activity in goldfish. The transcripts of Mc1r, but not those of other subtypes, were observed in xanthophores. ?-MSH, which has an acetyl group at the N-terminus, was found to disperse pigment in a dose-dependent manner in xanthophores. This potency was found to be slightly greater than that of desacetyl-?-MSH. These results support our findings that MCR has a higher affinity for ?-MSH when single Mcr subtype is expressed. On the other hand, transcripts of Mc2r, but not those of other subtypes, were observed in the head kidney. ACTH(1-24)-stimulated cortisol release was observed in a dose-dependent manner, while ?-MSH-related peptides showed no activity. It therefore appears that MC2R also acts as an ACTH-specific receptor in goldfish and that association of ?-MSH-related peptides upon release of cortisol is uncommon in fishes. PMID:21784075
Kobayashi, Yuki; Chiba, Hiroaki; Mizusawa, Kanta; Suzuki, Nobuo; Cerdá-Reverter, José Miguel; Takahashi, Akiyoshi
Known as the 'stress hormone,'cortisol is secreted at higher levels in the bloodstream during the body's 'fight or flight' response to stress as it is responsible for multiple stress related responses in the body. Moderate increases in cortisol levels can...
J. Crosbie J. Pitonyak L. M. Burrell M. D. Matthews
In order to characterize the individual diurnal plasma profiles of triiodothyronine (T3) and thyroxine (T4) in rainbow trout (Oncorhynchus mykiss), blood samples from 41 fish were taken every hour during a 24-hr period, through a catheter inserted into the dorsal aorta. The possible influences of day–night alternation, sex, and diet (feed intake, time of meals) on thyroid hormone (TH) profiles
J. M. Gomez; T. Boujard; G. Boeuf; A. Solari; P.-Y. Le Bail
The aim of this study was to determine whether glucocorticoid production could be monitored non-invasively in dromedary camels by measuring faecal cortisol metabolites (FCMs). Five Sudanese dromedaries, two males and three females, were injected with a synthetic adrenocorticotropic hormone (ACTH) analogue. Blood samples were collected pre- and post-ACTH injection. Faeces were sampled after spontaneous defecation for five consecutive days (2 days before and 3 days after ACTH injection). Baseline plasma cortisol values ranged from 0.6 to 10.8 ng/ml in males and from 1.1 to 16.6 ng/ml in females, while peak values after ACTH injection were 10.9-41.9 in males and 10-42.2 ng/ml in females. Peak blood cortisol values were reached between 1.5 and 2.0 h after ACTH injection. The concentration of FCMs increased after ACTH injection in the faeces of both sexes, although steroid levels peaked earlier in males [24 h; (286.7-2,559.7 ng/g faeces)] than in females [36-48 h; (1,182.6-5,169.1 ng/g faeces)], reflecting increases of 3.1-8.3- and 4.3-8-fold above baseline levels. To detect chromatographic patterns of immunoreactive FCMs, faecal samples with high FCM concentrations from both sexes were pooled and subjected to reverse phase high performance liquid chromatography (RP-HPLC). RP-HPLC analysis revealed sex differences in the polarity of FCMs, with females showing more polar FCMs than males. We concluded that stimulation of adrenocortical activity by ACTH injection resulted in a measurable increase in blood cortisol that was reliably paralleled by increases in FCM levels. Thus, measurement of FCMs is a powerful tool for monitoring the adrenocortical responses of dromedaries to stressors in field conditions. PMID:23430659
Sid-Ahmed, Omer-Elfaroug; Sanhouri, Ahmed; Elwaseela, Badr-Eldin; Fadllalah, Imad; Mohammed, Galal-Eldin Elazhari; Möstl, Erich
Objective: To determine the activity of cortisol in rats treated with exogenous adrenocorticotropic hormone (ACTH) and a resveratrol supplement. Methods: Forty-eight adult female rats and 16 male rats of the strain (Rattus norvegicus) that were three months old and with body weights ranging from 200 to 250 g for females and 300 to 350 g for males were used and kept in controlled environmental conditions: temperature of 20±2° C and light-dark cycles of 14 and 10 hours. They were fed a balanced diet and had free access to water. The rats were randomly divided into four groups: group 1 - was treated with 5 µg/kg of ACTH i.p. every twelve hours; group 2 - received the same treatment with ACTH plus a grape extract supplement (resveratrol) of 40 mg/kg; group 3 - only received grape extract (resveratrol); and group 4 - received a saline solution (0.9%) i.p. and oral, and served as controls. The experimental design was a 2×2 factorial with two levels ACTH and two polyphenol levels (grape extract). Results: No significant differences were found in blood cortisol concentrations, by day and gender, or by treatment effects (0.75 µg/dL ± 0.11; p <0.001). Conclusion: Results suggest that chronic stress and consumption of resveratrol did not directly alter levels of plasmatic cortisol in either stressed or unstressed rats. It was concluded that the given dosage levels of ACTH possibly did not produce sufficient stimulation of the adrenal gland for these animals.
Hurtado Salazar, Alejandro; Uribe-Velasquez, Luis F
...differential diagnosis and treatment of certain disorders of the adrenal glands such as Cushing's syndrome, adrenocortical insufficiency, and the ectopic ACTH syndrome. (b) Classification. Class...
...differential diagnosis and treatment of certain disorders of the adrenal glands such as Cushing's syndrome, adrenocortical insufficiency, and the ectopic ACTH syndrome. (b) Classification. Class...
We report a method, based on isotope dilution--mass spectrometry, for determining cortisol in a pooled specimen of human serum. Isotopically labeled cortisol is added to 5.0 mL of serum so that the molar concentrations of labeled cortisol and unlabeled cortisol are approximately equal. The specimen and two calibration standards are extracted with dichloromethane, and the extracted cortisol is converted to the methoxime-trimethylsilyl ether derivative. Samples and standards are analyzed by gas chromatography--mass spectrometry by monitoring the peak areas for m/z 605 and 608. The cortisol concentration is calculated by linear interpolation between the two bracketing standards. Variances of data collected during six weeks showed that the overall coefficient of variation (CV) was 0.69% (n . 32); the within-vial CV, 0.63%; the among-vial CV, 0.22%; and the among-day CV, 0.15% (means . 3.973 nmol/vial). Method specificity was demonstrated by liquid chromatographic as well as C/sub 8/ mini-column cleanup of samples before derivation, by alternative ion monitoring at m/z 636 and 639, and by negative-ion chemical ionization at m/z 459 and 462. Derivatives of all observed degradation products of cortisol under basic, neutral, and acidic conditions did not interfere.
Patterson, D.G.; Patterson, M.B.; Culbreth, P.H.; Fast, D.M.; Holler, J.S.; Sampson, E.J.; Bayse, D.D.
This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas.
Kolesnikova, G. S.; Lapshina, A. M.; Voronkova, I. A.; Marova, E. I.; Arapova, S. D.; Goncharov, N. P.; Dedov, I. I.
Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations—including obesity, metabolic syndrome, and cardiovascular disease—by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids.
Tomoshige Kino (NIH;Eunice Kennedy Shriver National Institute of Child Health and Human Development REV)
Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations—including obesity, metabolic syndrome, and cardiovascular disease—by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids.
The aim of this study was to investigate the response to 16 weeks of training on selected hormonal and biological parameters in seven international competition level female artistic gymnasts (14.5 +/- 1.2 years). Data were collected at the beginning of the first training week (W1) and in the 16th week (W16). Assessments also included anthropometric measurements, dietary intake for 7 days and Tanner staging. No gymnast had reached menarche and the puberty stages corresponded to Tanner's pubertal stage 2. The gymnasts were smaller than average for their age group, with a height:weight ratio above the 50th percentile. Energy intake was about 31% lower than recommendations. Significant decreases in IGF-I, IGFBP3, IGF-I:C ratio and triglyceride values and increases in uric acid and creatinine levels were noted. Cortisol values were high regardless of the period. This training provided evidence for alterations in resting somatotropic and adrenocorticotropic parameters. PMID:12880124
Filaire, E; Jouanel, P; Colombier, M; Bégue, R J; Lac, G
In response to stress, the hypothalamus releases cortiticotropin releasing hormone (CRH) that travels to the anterior pituitary, where it stimulates the release of adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal cortex, where it stimulates the release of cortisol and other steroids that liberate energy stores to cope with the stress. During pregnancy, the placenta synthesises CRH and releases it into the bloodstream at increasing levels to reach concentrations 1,000 to 10, 000 times of that found in the non-pregnant individual. Urocortins, which are CRH analogues are also secreted by the placenta. Desensitisation of the maternal pituitary to CRH and resetting after birth may be a factor in post-partum depression. Recently, CRH has been found to modulate glucose transporter (GLUT) proteins in placental tissue, and therefore there may be a link between CRH levels and foetal growth. Evidence suggests CRH is involved in the timing of birth by modulating signalling systems that control the contractile properties of the myometrium. In the placenta, cortisol stimulates CRH synthesis via activation of nuclear factor kappa B (NF-?B), a component in a cellular messenger system that may also be triggered by stressors such as hypoxia and infection, indicating that intrauterine stress could bring forward childbirth and cause low birth weight infants. Such infants could suffer health issues into their adult life as a result of foetal programming. Future treatment of these problems with CRH antagonists is an exciting possibility. PMID:23385670
Background Although bio-psycho-social health research is an ideal, samples adequate for complex modeling require biomarker specimens from hundreds of participants. Ecological sampling departs from laboratory study norms, with implications for analysis. Objective This paper compares salivary cortisol levels and effect sizes of ‘focal’ psychiatric factors, such as trauma history, posttraumatic stress diagnosis, comorbidity, and chronic stress, and ‘nuisance’ factors, including endocrine disorders, medications, physiological factors, such as gestational age, and smoking, to inform ecological study designs. Study Design This is a descriptive analysis of ecologically collected cortisol specimens, assayed in an on-going perinatal psychobiological study, addressing methodological considerations. Results Focal and nuisance factors are often interdependent with similar effect sizes. Careful specimen deletion decisions and model specification are needed to achieve the hoped-for external validity while maintaining internal validity. Conclusions Results of multivariate models support the validity and usefulness of an ecological approach to incorporating biomarkers in health research.
King, Anthony; Leichtman, Jennifer; Abelson, James; Liberzon, Israel; Seng, Julia S.
BACKGROUND: Although bio-psycho-social health research is an ideal, samples adequate for complex modeling require biomarker specimens from hundreds of participants. Ecological sampling departs from laboratory study norms, with implications for analysis.OBJECTIVE:To inform ecological study designs, this article compares salivary cortisol levels and effect sizes of “focal” psychiatric factors, such as trauma history, posttraumatic stress diagnosis, comorbidity, and chronic stress, and
Anthony P. King; Jennifer N. Leichtman; James L. Abelson; Israel Liberzon; Julia S. Seng
Steroidhormone und Peptidhormone beim atopischen Ekzem. Eine radioimmunologische Bestimmung der diurnalen Plasmakonzentrationsaenderungen von Testosteron, Cortisol, Prolaktin und human Growth Hormone bei gesunden Probanden und Patienten mit atopischem Ekzem. (Steroid hormones and peptide hormones in atopic eczema. Radioimmunological determination of diurnal plasma level variations of testosterone, cortisol, prolactin and human growth factor in healthy volunteers and patients showing atopic eczema).
An analysis of hormone measurements in sera from healthy volunteers and patients that was carried out on the basis of different criteria yielded the following results: (1) The testosterone levels determined in the patients sera were significantly lower th...
The aim of this study was to characterize the pituitary-interrenal axis in barfin flounder, a flatfish. Adrenocorticotropic hormone (ACTH) and melanocortin 2 receptor (MC2R) have been shown to be indispensable substances in pituitary and interrenal cells for cortisol release, respectively. We previously identified ACTH in the pars distalis of the barfin flounder pituitary gland, and detected transcripts of Mc1r, Mc4r, and Mc5r in the head kidney wherein interrenal cells are located. We have now demonstrated the presence of MC2R, which is a specific receptor for ACTH, in interrenal cells by molecular cloning of Mc2r cDNA and in situ hybridization, and confirmation of the in vitro cortisol-releasing activity of ACTH. These results show the presence of a classical pituitary-interrenal axis in this fish. We also evaluated the role of ?-melanocyte-stimulating hormone (?-MSH) and its related peptides. In situ hybridization was used to demonstrate the expression of Mc5r in interrenal cells; both desacetyl-?-MSH and diacetyl-?-MSH showed in vitro cortisol-releasing activities, while the activity of ?-MSH was negligible. These findings indicate the presence of an additional pituitary-interrenal axis consisting of ?-MSH-like peptides secreted from the neurointermediate lobe of the pituitary and MC5R in the interrenal cells. The cortisol-releasing activity of desacetyl-?-MSH and diacetyl-?-MSH, compared with the low activity of ?-MSH, suggest a unique and specific functional role of these forms of MSH peptides. The interrenal co-expression of two subtypes of Mcrs may play a role in this specialization. PMID:21118693
Kobayashi, Yuki; Chiba, Hiroaki; Yamanome, Takeshi; Schiöth, Helgi B; Takahashi, Akiyoshi
This study assessed the role of the extracellular signal-regulated kinase (ERK) signaling pathway on the previously observed enhanced cortisol secretion in response to adrenocorticotropic hormone (ACTH) treatment in fetal adrenocortical cells (FACs) from long-term hypoxic (LTH) ovine fetuses. Ewes were maintained at high altitude (3,820 m) from ~40 to 138-141 days gestation when FACs were collected and challenged with either ACTH (10 nM) or 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP, 10 mM) in the presence or absence of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK)/ERK inhibitor UO126 (10 ?M). FACs from age-matched normoxic fetuses served as controls. Media and FACs were collected at selected time intervals after ACTH or 8-bromo-cAMP stimulation for cortisol measurement and Western analysis of ERK1/2 and phospho-ERK1 and -2 (pERK1/2). After ACTH or 8-bromo-cAMP treatment, cortisol production was greater in the LTH group compared with control (P < 0.05). UO126 reduced ACTH and 8-bromo-cAMP-mediated cortisol output in both groups (P < 0.01 vs. ACTH or 8-bromo-cAMP alone). Under basal conditions, ERK1/2 and pERK1/2 were not different between LTH and normoxic fetuses. In response to ACTH or 8-bromo-cAMP treatment, ERK1/2 were not different between groups; however, pERK1/2 were elevated in the LTH FACs compared with normoxic control FACs. ERK1/2 phosphorylation declined following ACTH treatment in the control group, but UO126 had no effect on ERK1/2 compared with untreated levels. Both ACTH and 8-bromo-cAMP treatment resulted in a decline of protein levels. UO126 pretreatment virtually eliminated pERK1/2 expression. We conclude that basal ERK signaling in FACs is necessary for normal cortisol production and sustained pERK in LTH adrenals enhances cortisol production. PMID:23427082
Vargas, Vladimir E; Kaushal, Kanchan M; Monau, Tshepo R; Myers, Dean A; Ducsay, Charles A
This study assessed the role of the extracellular signal-regulated kinase (ERK) signaling pathway on the previously observed enhanced cortisol secretion in response to adrenocorticotropic hormone (ACTH) treatment in fetal adrenocortical cells (FACs) from long-term hypoxic (LTH) ovine fetuses. Ewes were maintained at high altitude (3,820 m) from ?40 to 138–141 days gestation when FACs were collected and challenged with either ACTH (10 nM) or 8-bromoadenosine 3?,5?-cyclic monophosphate (8-bromo-cAMP, 10 mM) in the presence or absence of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK)/ERK inhibitor UO126 (10 ?M). FACs from age-matched normoxic fetuses served as controls. Media and FACs were collected at selected time intervals after ACTH or 8-bromo-cAMP stimulation for cortisol measurement and Western analysis of ERK1/2 and phospho-ERK1 and -2 (pERK1/2). After ACTH or 8-bromo-cAMP treatment, cortisol production was greater in the LTH group compared with control (P < 0.05). UO126 reduced ACTH and 8-bromo-cAMP-mediated cortisol output in both groups (P < 0.01 vs. ACTH or 8-bromo-cAMP alone). Under basal conditions, ERK1/2 and pERK1/2 were not different between LTH and normoxic fetuses. In response to ACTH or 8-bromo-cAMP treatment, ERK1/2 were not different between groups; however, pERK1/2 were elevated in the LTH FACs compared with normoxic control FACs. ERK1/2 phosphorylation declined following ACTH treatment in the control group, but UO126 had no effect on ERK1/2 compared with untreated levels. Both ACTH and 8-bromo-cAMP treatment resulted in a decline of protein levels. UO126 pretreatment virtually eliminated pERK1/2 expression. We conclude that basal ERK signaling in FACs is necessary for normal cortisol production and sustained pERK in LTH adrenals enhances cortisol production.
Vargas, Vladimir E.; Kaushal, Kanchan M.; Monau, Tshepo R.; Myers, Dean A.
Objective: The purpose of this study was to determine if children with fragile X syndrome, who typically demonstrate a neurobehavioral phenotype that includes social anxiety, withdrawal, and hyper-arousal, have increased levels of cortisol, a hormone associated with stress. The relevance of adrenocortical activity to the fragile X phenotype also was examined.Method: One hundred and nine children with the fragile X
D. Hessl; B. Glaser; J. Dyer-Friedman; C. Blasey; T. Hastie; M. Gunnar; A. L. Reiss
Cortisol in obesity is a much-studied problem. Previous information indicates that cortisol secretion is elevated but that circulatory concentrations are normal or low, suggesting that peripheral disappearance rate is elevated. These studies have usually not taken into account the difference between central and peripheral types of obesity. Recent studies using saliva cortisol have indicated that the problem is complex with
Per Björntorp; Roland Rosmond
Milking-related release of oxytocin, prolactin, and cortisol was studied following three premilking treatments. Six Murrah buffaloes were treated with direct application of milking cluster (O), a 1-min pre-stimulation (M), and combined feeding and pre-stimulation (MF). Machine milk yield, stripping yield and milk composition were recorded. Milk ejection occurred significantly earlier with MF than M and O (P<0.05; 2.50, 5.10 and 6.33 min, respectively). In all treatments, milk ejection occurred with small increases >3-5 ng/l in oxytocin concentration. Increase in oxytocin concentration over a threshold level and milk ejection occurred simultaneously and were closely correlated (r=0.83, P<0.05). There was a positive correlation between total time oxytocin concentration remained elevated over threshold levels and machine yield (r=0.86, P<0.05). For treatment O, milk ejection was inhibited during machine milking, while a marked increase in oxytocin occurred during hand stripping (6 and 16 ng/l, respectively). For treatment M, mean oxytocin concentrations remained unchanged during prestimulation but increased during subsequent machine milking and hand stripping (6.38, 18.06 and 12.36 ng/l, respectively). For treatment MF, although there was a 3.6-fold increase during pre-stimulation, oxytocin increased by 10-fold and 3-fold during machine milking and hand stripping, and was significant for machine milking (P<0.05, 17.32, 47.86, 18.13 ng/l, respectively). Milk-ejection-related cortisol release was visible only in treatment MF. For treatments O and M, prolactin concentration increased prior to the increase in oxytocin. The stripping yield was higher, and fat content in the stripping yield significantly lower, for treatment O indicating incomplete milking. Thus buffaloes are easily disturbed even by small changes in milking routines. PMID:15747726
Thomas, Chirathalattu S; Bruckmaier, Rupert M; Ostensson, Karin; Svennersten-Sjaunja, Kerstin
Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne. PMID:23619437
Cortisol bound to corticosteroid binding globulin (CBG) contributes up to 90% of the total cortisol concentration in circulation. Therefore, changes in the binding kinetics of cortisol to CBG can potentially impact on the concentration of free cortisol, the only form that is responsible for the physiological function of the hormone. When CBG is cleaved into elastase-cleaved CBG (eCBG) by the activity of neutrophil elastase, its affinity for cortisol is reduced. Therefore, when eCBG coexists with intact CBG (iCBG) in plasma, the calculation of free cortisol concentration based on the formulae that considers only one CBG pool with the same affinity for cortisol may be inappropriate. In this study, we developed in vivo and in vitro models of cortisol partitioning which considers two CBG pools, iCBG and eCBG, with different affinities for cortisol, and deduce a new formula for calculating plasma free cortisol concentration. The formula provides better estimates of free cortisol concentration than previously used formulae when measurements of the concentrations of the two CBG forms are available. The model can also be used to estimate the affinity of CBG and albumin for cortisol in different clinical groups. We found no significant difference in the estimated affinity of CBG and albumin for cortisol in normal, sepsis and septic shock groups, although free cortisol was higher in sepsis and septic shock groups. The in vivo model also demonstrated that the concentration of interstitial free cortisol is increased locally at a site of inflammation where iCBG is cleaved to form eCBG by the activity of elastase released by neutrophils. This supports the argument that the cleavage of iCBG at sites of inflammation leads to more lower-affinity eCBG and may be a mechanism that permits the local concentration of free cortisol to increase at these sites, while allowing basal free cortisol concentrations at other sites to remain unaffected. PMID:24373796
Nguyen, Phuong T T; Lewis, John G; Sneyd, James; Lee, Rita S F; Torpy, David J; Shorten, Paul R
Purpose: Abnormalities in both cortisol and dehydroepiandrosterone (DHEA) have been reported in psychiatric disorders. Analysis of saliva, urine and blood cortisol and DHEA levels provides an index of hormone levels over a short time period. Unlike such conventional measures, fingernails incorporate endogenous hormones that passively diffuse to the nail matrix from capillaries during keratinization. This study piloted the measurement of cortisol and DHEA levels in fingernails as a potential measure of their accumulated secretion of steroid hormones over a prolonged time period. Method: Thirty-three university students (18–24 years) provided fingernail samples on two occasions over a school semester. The visits were scheduled so nail cortisol and DHEA levels were collected from periods when students might be under different levels of stress. Results: During the putatively stressful period, the nail samples showed a significant increase in the cortisol: DHEA ratio (P = 0.0002) due to a significant decrease in the DHEA levels (P = 0.004) and a numerical but not statistically significant increase in the cortisol levels (P = 0.256). Discussion: This pilot study showed that nails can be used to measure cortisol and DHEA, a measure which may reflect environmental stress. More work is required to further validate this technique which may prove useful in studies of both healthy individuals and patient groups.
Warnock, Fay; McElwee, Kevin; Seo, Rubo J; McIsaac, Sean; Seim, Danielle; Ramirez-Aponte, Tatiana; Macritchie, Karine AN; Young, Allan H
The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i) compressed sensing for recovering the amplitude and timing of the secretory events, and (ii) generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R2 above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i) quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii) potentially designing optimal approaches for treating hormonal disorders.
Faghih, Rose T.; Dahleh, Munther A.; Adler, Gail K.; Klerman, Elizabeth B.; Brown, Emery N.
Aldosterone and cortisol are the two major hormones secreted by the human adrenal cortex. Exercise is one of the stresses known to increase the levels of both of these hormones, although the intensity of exercise needed to elicit secretion is different fo...
M. J. Buono J. E. Yeager
Treatment of fetal rats and embryonic chickens with exoge- nous glucocorticoids induces premature GH cell differentia- tion. However, it is unknown whether the developing adrenal glandiscapableofmountingthisresponseautonomously.The present study determined whether stimulation of the adrenal gland in developing chicken embryos through administration of ACTH could induce a premature increase in GH cells. We found that plasma corticosterone and ACTH levels increased
S. A. Jenkins; M. Muchow; M. P. Richards; J. P. McMurtry; T. E. Porter
Summary Modest genetic effects on morning, but not late-day, cortisol levels have been established. Environmental demands may influence basal cortisol levels later in the day. Thus, we anticipated that individuals in the same family would have similar afternoon cortisol levels to the extent that they share aspects of their environment. We examined afternoon basal cortisol levels measured across three consecutive days in mothers and fathers and in multiple offspring in two separate large, longitudinal studies. Study I involved 321 families with singletons while study II involved 233 families with twins. Modest family similarity was apparent for afternoon basal cortisol levels in both studies. Spouses’ cortisol levels were also correlated. Data from Study II demonstrated that family resemblance in afternoon cortisol was accounted for by underlying shared environmental factors but not underlying genetic factors. Shared environment accounted for 62% of the variation in twin afternoon basal cortisol levels and 14% of the variation in parent afternoon basal cortisol levels. We used pooled data from the two studies to examine whether parental depression, socioeconomic status (SES), and offspring sex and age impacted cortisol levels. Female offspring had higher cortisol levels than males, and cortisol decreased with age until about nine years of age, after which cortisol increased with age. Family similarity persisted after accounting for parental depression, SES, time of day, and offspring sex and age, which suggests that the shared family environment influences parent and offspring stress hormone levels throughout the childhood years.
Schreiber, Jane E.; Shirtcliff, Elizabeth; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Klein, Marjorie H.; Kalin, Ned H.; Essex, Marilyn J.; Goldsmith, H. Hill
Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic–pituitary–adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a novel environment; and (3) in response to a blood draw stressor. A significantly higher serum cortisol response was found in the group of children with autism. Analysis showed significantly higher peak cortisol levels and prolonged duration and recovery of cortisol elevation following the blood-stick stressor in children with autism. This study suggests increased reactivity of the HPA axis to stress and novel stimuli in children with autism.
Spratt, Eve G.; Nicholas, Joyce S.; Brady, Kathleen T.; Carpenter, Laura A.; Hatcher, Charles R.; Meekins, Kirk A.; Furlanetto, Richard W.; Charles, Jane M.
This study tested the hypothesis that the sexually dimorphic adrenocortical response to stress is already established before birth. Chronically instrumented late gestation pregnant sheep carrying 16 male and 15 female age-matched singleton fetuses were subjected to an acute episode of hypoxic stress. Maternal and fetal blood gases, adrenocorticotrophic hormone (ACTH), and cortisol were measured. In addition, six male and six female fetuses received the ACTH analog, Synacthen, and plasma cortisol was measured. During hypoxic stress, the increment in plasma cortisol was 2-fold greater in male versus females fetuses (30.6 ± 3.2 versus 14.3 ± 2.0 ng/mL; p < 0.001) mediated, in part, by greater adrenocortical sensitivity to ACTH. The data support the hypothesis tested and show that sex-specific differences in the cortisol stress response are present before birth with the output of cortisol being much greater in male than in female fetuses. PMID:21045750
Giussani, Dino A; Fletcher, Andrew J W; Gardner, David S
Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone\\u000a reflecting hypothalamic–pituitary–adrenal (HPA) axis activity, in children with autism have demonstrated variable results.\\u000a This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a novel environment; and (3)\\u000a in response to a blood draw stressor. A
Eve G. Spratt; Joyce S. Nicholas; Kathleen T. Brady; Laura A. Carpenter; Charles R. Hatcher; Kirk A. Meekins; Richard W. Furlanetto; Jane M. Charles
There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly
Michael Maes; Dirk van West; Nathalie De Vos; Herman Westenberg; Fran Van Hunsel; Dirk Hendriks; Paul Cosyns; Simon Scharpé
For decades, congenital panhypopituitarism has been recognized to cause infantile cholestasis. However, the identity of the hormone whose deficiency causes such derangement of the liver is not clear. Here, we report four cases of isolated severe cortisol deficiency presenting with neonatal cholestasis and hypoglycemia, of whom two had familial primary glucocorticoid deficiency and the other two had isolated adrenocorticotropin deficiency. The resolution of cholestasis by hydrocortisone replacement therapy suggests a causal relationship between cortisol deficiency and the development of neonatal cholestasis. In conclusion, the presentation of a young infant with cholestasis and hypoglycemia should alert pediatricians to the possibility of cortisol deficiency and prompt investigation of adrenal function should be undertaken.
Al-Hussaini, Abdulrahman; Almutairi, Awatif; Mursi, Alaaddin; Alghofely, Mohammed; Asery, Ali
Aims 3,4-Methylenedioxymethamphetamine (MDMA) can affect both neurotransmitter and neurohormonal activity. This review will debate the role of the metabolic activation hormone cortisol for the psychobiological effects of ecstasy/MDMA. Methods The empirical literature on cortisol release following acute MDMA administration and cortisol functioning in drug-free recreational ecstasy/MDMA users will be reviewed. This will be followed by an overview of cortisol as a bioenergetic stress neurohormone, and a debate on how it could be modulating the acute and chronic psychobiological effects of MDMA. Results Cortisol release is increased by stimulatory factors, including physical activity, thermal stress and stimulant drugs. In laboratory studies MDMA leads to an acute cortisol increase of around 150% in sedentary humans. In MDMA-using dance clubbers, the cortisol levels are increased by around 800%, possibly due to the combined factors of stimulant drug, physical exertion and psychosocial stimulation. Regular ecstasy/MDMA users also demonstrate changes in baseline cortisol levels and cortisol reactivity, with compromised hypothalamic-pituitary-adrenal activity. Nonpharmacological research has shown how cortisol is important for psychological aspects such as memory, cognition, sleep, impulsivity, depression and neuronal damage. These same functions are often impaired in recreational ecstasy/MDMA users, and cortisol may be an important modulatory co-factor. Conclusions The energizing hormone cortisol is involved in the psychobiology of MDMA, probably via its effects on energy metabolism. Acute cortisol release may potentiate the stimulating effects of MDMA in dance clubbers. Chronically, cortisol may contribute to the variance in functional and structural consequences of repeated ecstasy usage.
Chronic psychological stress is associated with accelerated aging, but the underlying biological mechanisms are not known. Prolonged elevations of the stress hormone cortisol is suspected to play a critical role. Through its actions, cortisol may potentially induce oxidatively generated damage to cellular constituents such as DNA and RNA, a phenomenon which has been implicated in aging processes. We investigated the
Anders Joergensen; Kasper Broedbaek; Allan Weimann; Richard D. Semba; Luigi Ferrucci; Martin B. Joergensen; Henrik E. Poulsen
In young male volunteers, the changes in growth hormone (GH), prolactin (PRL), and adrenocorticotropic hormone (ACTH) release in response to insulin injection combined with the infusion of saline, glucose, and fructose were evaluated. Glucose infusion in a dose which prevented insulin hypoglycemia completely abolished endocrine responses. Infusion of fructose, which is known not to cross the blood-brain barrier (BBB), did not influence the GH release during hypoglycemia; however, it inhibited PRL secretion. The ACTH response was slightly attenuated and delayed, while the hypoglycemia-induced rise in cortisol levels was not modified by fructose infusion. These data indicate that the glucoreceptors mediating the signals for a complete counterregulatory neuroendocrine response are not located in a single brain structure. Stimuli for GH release are produced in areas of the central nervous system protected by the BBB, while those for PRL release are presumably present in structures not protected by the BBB. Glucoreceptors triggering ACTH release are located both inside and outside the BBB. PMID:2157998
Vigas, M; Tatár, P; Jurcovicová, J; Jezová, D
The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), beta-endorphin (beta EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D0), and before and after each day's racing (D1-D6). The mean daily heart rate (fc) was calculated from fc values recorded every minute during the race. The results showed the following: changes in mean fc [from 147 (SEM 3) to 156 (SEM 3) beats.min-1 according to the day] were not significant during the race. Diurnal variations in ACTH, beta EP and C were no longer apparent after the race: evening levels were higher than their respective D0 values during the race, except on D3 when there was a lack of response to exercise in the three hormones. Unlike ACTH and beta EP, pre- and postexercise C values on D1 and D2 were higher than those on the subsequent days (P less than 0.001). In contrast, there was a progressive accumulation of A and NA in pre- and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and beta EP were found especially on D3 and D6 (P less than 0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1314173
Fellmann, N; Bedu, M; Boudet, G; Mage, M; Sagnol, M; Pequignot, J M; Claustrat, B; Brun, J; Peyrin, L; Coudert, J
Interpersonal touch is a fundamental component of social interactions because it can mitigate physical and psychological distress. To reproduce the psychological and physiological effects associated with interpersonal touch, interest is growing in introducing tactile sensations to communication devices. However, it remains unknown whether physical contact with such devices can produce objectively measurable endocrine effects like real interpersonal touching can. We directly tested this possibility by examining changes in stress hormone cortisol before and after a conversation with a huggable communication device. Participants had 15-minute conversations with a remote partner that was carried out either with a huggable human-shaped device or with a mobile phone. Our experiment revealed significant reduction in the cortisol levels for those who had conversations with the huggable device. Our approach to evaluate communication media with biological markers suggests new design directions for interpersonal communication media to improve social support systems in modern highly networked societies.
Sumioka, Hidenobu; Nakae, Aya; Kanai, Ryota; Ishiguro, Hiroshi
Police officers are required to work irregular hours, which induces stress, fatigue, and sleep disruption, and they have higher rates of chronic disease and mortality. Cortisol is a well-known "stress hormone" produced via activation of the hypothalamic-pituitary-adrenal axis. An abnormal secretion pattern has been associated with immune system dysregulation and may serve as an early indicator of disease risk. This study examined the effects of long- and short-term shiftwork on the cortisol awakening response among officers (n = 68) in the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study (2001-2003). The time each officer spent on day (start time: 04:00-11:59 h), afternoon (12:00-19:59 h), or night (20:00-03:59 h) shifts was summarized from 1994 to examination date to characterize long-term (mean: 14 ± 9 yrs) and short-term (3, 5, 7, or 14 days prior to participation) shiftwork exposures. The cortisol awakening response was characterized by summarizing the area under the curve (AUC) for samples collected on first awakening, and at 15-, 30-, and 45-min intervals after waking. Data were collected on a scheduled training or off day. The cortisol AUC with respect to ground (AUC(G)) summarized total cortisol output after waking, and the cortisol AUC with respect to increase (AUC(I)) characterized the waking cortisol response. Officers also completed the Center for Epidemiologic Studies Depression scale. Waking cortisol AUC values were lower among officers working short-term night or afternoon shifts than day shifts, with maximal differences occurring after 5 days of shiftwork. The duration of long-term shiftwork was not associated with the cortisol awakening response, although values were attenuated among officers with more career shift changes. PMID:21721860
Wirth, Michael; Burch, James; Violanti, John; Burchfiel, Cecil; Fekedulegn, Desta; Andrew, Michael; Zhang, Hongmei; Miller, Diane B; Hébert, James R; Vena, John E
Mammary tissue explants from four nonlactating, nonpregnant cows were placed into culture with media containing various combinations of insulin, prolac- tin, growth hormone, 17~-estradiol, dexa- methasone, and progesterone. Combina- tions of insulin, prolactin, growth hor- mone, or 17~-estradiol had no effect on cytoplasmic or nuclear uptake of tritiated cortisol compared with values at zero time. Combinations containing dexa- methasone or
R. J. Collier; H. Allen Tucker
Post-immigration adaptation is characterized by chronic and acute acculturative stressors. Salivary cortisol is a commonly used hormonal marker of stress, but few studies have investigated its use as an indicator of acculturative stress and adjustment in immigrants. The purpose of this study was to examine relationships among predictors of adjustment (environmental and language mastery), self-reported stress outcomes (depressive symptoms, perceived stress, alienation), and salivary cortisol response in immigrants from the former Soviet Union. The sample included 137 married men and women aged 42-80 who lived in the U.S. for 1-13 years. Results indicated that while men and women had similar values for cortisol response, relationships among adjustment measures, stress outcomes, and cortisol differed by gender. Among men, environmental mastery significantly reduced depressive symptoms, perceived stress, and cortisol response. Among women, environmental mastery also reduced depressive symptoms, perceived stress, and alienation, but language mastery increased cortisol response and decreased alienation. PMID:23224773
Nicholson, Lisa M; Miller, Arlene Michaels; Schwertz, Dorie; Sorokin, Olga
Introduction – Biological, hematological, nutritional, psychological parameters and hormone productions from the gonadotropic, somatotropic, and adrenocorticotropic axis have been examined in seven international level gymnasts (14.5 ± 1.2 years) from a National Gymnastic Institute.Methods – To explore the hormonal, biological and metabolic characteristics of the gymnasts resting blood samples were collected from an antecubital vein (700 hours) after an overnight
E. Filaire; C. Ferrand; P. Jouanel; M. Colombier; R. J. Bégue; G. Lac
It is well known that after a stressor, levels of plasma cortisol rise, inducing physiological changes within the animal that are directed toward maintaining homeostasis. Less well understood is the role of cortisol in regulating food intake in teleosts. This study investigated the effect of cortisol on food intake and regulation of the neuroendocrine appetite-stimulating hormones, neuropeptide Y (NPY) and ghrelin, in tilapia (Oreochromis mossambicus). Male and female tilapia were randomly assigned to one of the following treatments: unhandled control, vehicle-injected control, or cortisol (2 ?g/g BW). Food intake was determined 24 h after injection during a 1-h feeding trial. Cortisol reduced food intake (P<0.001). An identical study was conducted to measure the effects of 24-h cortisol treatment on the endocrine regulators of food intake. Cortisol reduced stomach expression of ghrelin mRNA (P<0.05) and plasma concentrations of ghrelin (P<0.05). In the hypothalamus/optic tectum cortisol reduced levels of GHSR1a-LR (biologically active ghrelin receptor) mRNA. In the telencephalon/preoptic area cortisol significantly reduced levels of NPY and GHSR1b-LR (biologically inactive ghrelin receptor) mRNA. These findings suggest that anorexigenic actions of cortisol may be mediated via two separate pathways: (1) reducing circulating ghrelin levels as well as GHSR1a-LR expression in the hypothalamus/optic tectum and/or (2) suppressing NPY expression in the telencephalon/preoptic area. PMID:22657576
Janzen, W J; Duncan, C A; Riley, L G
Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study
This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).
Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.
Most psychosocial stress studies assess the overall cortisol response without further identifying the temporal dynamics within hormone levels. It has been shown, however, that the amplitude of anticipatory cortisol stress levels has a unique predictive value for psychological health. So far, no "best practice" in how to investigate the anticipatory cortisol stress response has emerged. The goal of the current research was to develop a protocol that would allow for a sensitive and easy-to-implement laboratory-based investigation into anticipatory cortisol stress levels. We initially tested 26 healthy men in either an anticipation- or stress-only condition of the Trier Social Stress Test (TSST) to map the distinct timelines of anticipatory and reactive cortisol release profiles (study 1). Subsequently, we administered the TSST to 50 healthy men such that the cortisol responses to anticipatory and reactive stress components could be dissociated (study 2). In both studies we sampled saliva cortisol at high frequency (at baseline, during 10min of anticipation and during and after 10min of acute stress) and the current mood state pre- and post-stress. We found anticipatory responder rates of 20% and 40%, with peak anticipatory cortisol levels between 14 and 20min after onset of anticipation. Visible changes in reactive cortisol levels occurred only after the termination of the acute stressor. We conclude that the best practice to detect a maximum number of anticipatory responders in the TSST would be to extend the anticipation phase to 15min. In doing so, the anticipatory cortisol peak could be captured at a time-point of the actual stressor that is uninfluenced by reactive cortisol levels. Overall, we could reveal several features of anticipatory responders. Most importantly, there was a positive correlation between anticipatory and reactive stress responses. There was no association between anticipatory cortisol and alpha-amylase as well as subjective-psychological stress responses. Future studies will have to determine whether the anticipatory responders differ with respect to various stress-sensitive parameters like sex, personality, psychological wellbeing or chronic stress. PMID:23246327
Engert, Veronika; Efanov, Simona I; Duchesne, Annie; Vogel, Susanne; Corbo, Vincent; Pruessner, Jens C
It is often difficult for instructors teaching laboratory courses in behavioral neuroscience to find appropriate experiments that can ethically examine biological parameters in human participants. In most instances, the default experiments that allow students to act as both experimenter and subject tend to be electrophysiological in nature (e.g., EEG, GSR, etc.). We report here the use of an experiment module that utilizes an easily-obtained enzyme immunoassay (EIA) kit to measure human salivary cortisol. Cortisol is a hormone of the adrenal cortex that can be used as a peripheral indicator of hypothalamic neural activity. Plasma (and salivary) cortisol levels rise due to circadian influences as well as perturbations in the organism's environment (i.e., stressors). The involvement of the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of depression makes this an appealing module to students in behavioral neuroscience laboratories. Measurement of salivary cortisol takes advantage of a simple, painless, non-invasive sampling procedure. The assay can be performed successfully by anyone with access to a plate reader, a shaker or rotary mixer, and a few commonly used pipettors. A single plate assay can be completed in two to three hours. Students in our behavioral neuroscience laboratory class have utilized this kit successfully to examine the circadian cortisol rhythm as well as the effect of stress/relaxation on cortisol levels. PMID:23493518
Kalman, Brian A; Grahn, Ruth E
The release of adrenal steroids during acute stress is primarily regulated by adrenocorticotropic hormone (ACTH). In contrast, during chronic inflammatory stress additional factors are involved in regulating adrenal function. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that increases ACTH release from the pituitary. In addition, LIF and LIF receptors (LIFR) are expressed in the human adrenal cortex and the
Alison M. Woods; Christopher J. McIlmoil; Ernestina N. Rankin; Alissa A. Packer; Jessica C. Stevens; Jeffrey A. Macievic; Aaron B. Brown; James P. Porter; Allan M. Judd
Hormones of the hypothalamus-pituitary-adrenal (HPA) axis have been considered to form part of an efferent humoral system modulating central nervous stimulus processing. The present experiments were designed to compare the effects of iv bolus administrations of placebo, porcine ACTH 1-39 (1.5 U) and h-CRH (25 micrograms) on auditory evoked potentials (AEPs) in healthy men. Also, cardiovascular parameters, cortisol and self-reported mood were assessed. ACTH significantly reduced the amplitude of the N1 component of the AEP; P1 and P2 remained unchanged. The selective reduction of N1 amplitude defies an interpretation of the changes in terms of a reduced stimulus-induced cortical arousal following ACTH; the ACTH-induced changes may rather indicate an influence on frontocortical functions of directing attention. The effect of ACTH on N1 cannot be attributed to its adrenocorticotropic action or to cardiovascular changes, but appears to represent an intrinsic extraadrenal influence of the hormone. The data do not provide evidence for effects of h-CRH on central nervous stimulus processing in humans, after peripheral administration. PMID:2160665
Born, J; Bathelt, B; Pietrowsky, R; Pauschinger, P; Fehm, H L
Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems.
Brown, E. N.; Meehan, P. M.; Dempster, A. P.
It has been shown that cortisol concentrations change characteristically in the course of agonistic interactions; our aim was to find out how a playful situation may affect concentrations of this hormone in the saliva. We studied dogs' behavior and the changes of cortisol concentrations in a play situation, where the dogs played with their handler for 3 min with a tug
Zsuzsánna Horváth; Antal Dóka; Ádám Miklósi
Background The harbour porpoise is exposed to increasing pressure caused by anthropogenic activities in its marine environment. Numerous offshore wind farms are planned or under construction in the North and Baltic Seas, which will increase underwater noise during both construction and operation. A better understanding of how anthropogenic impacts affect the behaviour, health, endocrinology, immunology and physiology of the animals is thus needed. The present study compares levels of stress hormones and mRNA expression of cytokines and acute-phase proteins in blood samples of harbour porpoises exposed to different levels of stress during handling, in rehabilitation or permanent human care. Free-ranging harbour porpoises, incidentally caught in pound nets in Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in Harderwijk, the Netherlands, and individuals permanently kept in human care in the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL-10 and TNF?, acute-phase proteins haptoglobin and C-reactive protein and the heat shock protein HSP70) were measured using real-time PCR. Results Biomarker expression levels varied between free-ranging animals and porpoises in human care. Hormone and cytokine ranges showed correlations to each other and to the health status of investigated harbour porpoises. Hormone concentrations were higher in free-ranging harbour porpoises than in animals in human care. Adrenaline can be used as a parameter for the initial reaction to acute stress situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators for the following minutes of acute stress. There is evidence for different correlations between production of normetanephrine, metanephrine, cortisol and the expression of IL-10, HSP70 and haptoglobin. Conclusions The expression patterns of the selected molecular biomarkers of the immune system are promising to reflect the health and immune status of the harbour porpoise under different levels of stress.
Background. Cortisol is a stress-related hormone with a robust circadian rhythm where levels typically peak in the morning hours and decline across the day. Although acute cortisol increases resulting from stressors are adaptive, chronic elevated cortisol levels are associated with poor functioning. Studies have shown age-related changes in cortisol levels. The present study investigated the relationship between salivary diurnal cortisol and functional outcomes among older adults undergoing inpatient post-acute rehabilitation. Methods. Thirty-two older adults (mean age 78 years; 84% men) in a Veterans Administration inpatient post-acute rehabilitation unit were studied. Functional outcomes were assessed with the motor component of the Functional Independence Measure (mFIM; where mFIM change = discharge ? admission score). Saliva samples were collected on 1 day at wake time, 45 minutes later, 11:30 AM, 2 PM, 4:30 PM, and bedtime. We analyzed the relationship between cortisol measures and functional outcomes, demographics, and health measures. Results. The analyses consistently showed that greater functional improvement (mFIM change) from admission to discharge was associated with lower comorbidity scores and higher cortisol levels at 2 PM, 4:30 PM, and bedtime. A morning cortisol rise was also associated with greater mFIM change. Conclusions. Measurement of cortisol in saliva may be a useful biological marker for identification of patients who are “at risk” of lower benefits from inpatient rehabilitation services and who may require additional assistance or intervention during their post-acute care stay.
Fiorentino, Lavinia; Saxbe, Darby; Alessi, Cathy A.; Woods, Diana Lynn
BACKGROUND: Variability in hypothalamic-pituitary-adrenal (HPA) axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS) and Large White (LW) pigs, MS being reported
Dominique Hazard; Laurence Liaubet; Magali SanCristobal; Pierre Mormède
Adult Leydig cell steroidogenesis is dependent on LH but fetal Leydig cells can function independently of gonadotropin stimulation. To identify factors that may be involved in reg- ulation of fetal Leydig cells expressed sequence tag libraries from fetal and adult testes were compared, and fetal-specific genes identified. The ACTH receptor (melanocortin type 2 receptor (Mc2r)) was identified within this fetal-specific
P. J. O'Shaughnessy; L. M. FLEMING; G. JACKSON; U. HOCHGESCHWENDER; P. REED
Glucocorticoids are known to hinder somatic growth in a number of vertebrate species. In order to better understand the mechanisms through which they may act in channel catfish, we examined the effects of feeding cortisol on the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein (IGFBP) network. Fish (30.6+/-3.0 g) were fed once daily for 4 weeks and treatments included: (1) High-cortisol (dietary cortisol provided at 400 mg/kg feed), (2) Low-cortisol (dietary cortisol provided at 200 mg/kg feed), and (3) Control (commercial catfish feed). Fish fed diets with cortisol weighed approximately 50% less than Controls. Feed intake was reduced by approximately 30% in both treatments of cortisol fed fish compared to Controls. A approximately 20-kDa IGFBP was observed in plasma from High- and Low-treated fish while it was not detected in Control fish plasma. High-cortisol treatment increased pituitary GH mRNA expression approximately 10-fold while liver IGF-I mRNA expression was not different between cortisol-treated fish and Controls. Cortisol treatments decreased plasma levels of IGF-I. These data indicate that feeding cortisol for 4 weeks reduces weight gain, feed intake, and plasma levels of IGF-I and induces a approximately 20-kDa IGFBP. One mechanism through which cortisol may impede growth of catfish is through an increase in a low molecular weight IGFBP which may lead to inhibitory effects on the action of IGF-I. PMID:15826774
Peterson, Brian C; Small, Brian C
Everyday lifestyle related issues are the main cause of psychological stress, which contributes to health disparities experienced by individuals. Prolonged exposure to stress leads to the activation of signaling pathways from the brain that leads to release of cortisol from the adrenal cortex. Various biomarkers have been affected by psychological stress, but cortisol "a steroid hormone" is known as a potential biomarker for its estimation. Cortisol can also be used as a target analyte marker to determine the effect of exposure such as organophosphates on central nervous system, which alters the endocrine system, leading to imbalance in cortisol secretion. Cortisol secretion of individuals depends on day-night cycle and field environment hence its detection at point-of-care (POC) is deemed essential to provide personalized healthcare. Chromatographic techniques have been traditionally used to detect cortisol. The issues relating to assay formation, system complexity, and multistep extraction/purification limits its application in the field. In order to overcome these issues and to make portable and effective miniaturized platform, various immunoassays sensing strategies are being explored. However, electrochemical immunosensing of cortisol is considered as a recent advancement towards POC application. Highly sensitive, label-free and selective cortisol immunosensor based on microelectrodes are being integrated with the microfluidic system for automated diurnal cortisol monitoring useful for personalized healthcare. Although the reported sensing devices for cortisol detection may have a great scope to improve portability, electronic designing, performance of the integrated sensor, data safety and lifetime for point-of-care applications, This review is an attempt to describe the various cortisol sensing platforms and their potential to be integrated into a wearable system for online and continuous monitoring of cortisol rhythm at POC as a function of one's environment. PMID:24212052
Kaushik, Ajeet; Vasudev, Abhay; Arya, Sunil K; Pasha, Syed Khalid; Bhansali, Shekhar
Background: Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic–pituitary–adrenal (HPA) axis function. Objective: We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor administered to Pb-exposed workers. Methods: Seventy male participants completed the Trier Social Stress Test (TSST). Serum cortisol (CORT) and plasma adrenocorticotropic hormone (ACTH) were assessed in response to and during recovery from the stressor. We measured Pb in blood, a biomarker of recent exposure, and in tibia bone by X-ray fluorescence (XRF), a biomarker of chronic exposure. Results: The TSST induced statistically significant increases in ACTH and CORT in the participants. At baseline, ACTH was not significantly higher (p = 0.052) in participants with higher blood Pb concentration, but CORT was significantly lower in these participants (p = 0.016). Adjusted linear regression models indicated a positive association between blood and bone Pb and the increase in ACTH in response to stress. However, Pb was not strongly associated with changes in CORT in response to stress. Pb was also associated with the ACTH:CORT ratio at baseline and throughout the course of the protocol, suggesting an adrenal hyporesponsiveness in participants with higher Pb concentrations. Conclusion: The altered HPA-axis stress response observed in participants exposed to higher levels of Pb further supports the idea that lead may contribute to a host of biological dysfunctions beyond the classical neurotoxic effects.
Fortin, Marie C.; Cory-Slechta, Deborah A.; Ohman-Strickland, Pamela; Nwankwo, Chizoba; Yanger, T. Steven; Todd, Andrew C.; Moynihan, Jan; Walton, James; Brooks, Andrew
A radioimmunoassay for cortisol has been developed using a cortisol-21-succinyl-bovine serum albumin conjugate injected into rabbits to produce anticortisol antibodies. The assay was physiologically validated by determining the resting cortisol levels in ...
H. C. Campuzano J. E. Wilkerson P. B. Raven T. Schabram S. M. Horvath
Healthy individuals tend to consume available rewards like food and sex. This tendency is attenuated or amplified in most stress-related psychiatric conditions, so we asked if it depends on endogenous levels of the 'canonical stress hormone' cortisol. We unobtrusively quantified how hard healthy heterosexual men would work to consume erotic images of women versus men and also measured their exposure to endogenous cortisol in the prior two months. We used linear models to predict the strength of sexual preference from cortisol level, after accounting for other potential explanations. Heterosexual preference declines with self-reported anhedonia but increases with long term exposure to endogenous cortisol. These results suggest that cortisol may affect reward-related behavior in healthy adults. PMID:24732415
Chumbley, J R; Hulme, O; Köchli, H; Russell, E; Van Uum, S; A Pizzagalli, D; Fehr, E
Controversy over the adaptive significance of male hunting in subsistence societies hinges on the relative importance of familial provisioning and mate-quality signalling. This paper examines the proximate and ultimate motivations of hunting behaviour from a neuroendocrine perspective, using salivary testosterone and cortisol data collected before, during and after hunting focal follows from 31 Tsimane hunters aged 18-82 years. Despite circadian declines in hormone levels, testosterone and cortisol of Tsimane hunters increased at the time of a kill, and remained high as successful hunters returned home. Previous studies of hormonal changes during competitions find that high-stakes and success in the presence of relevant audiences result in increased neuroendocrine arousal. If men hunt primarily to provision their families, then an additional audience would not be expected to impact testosterone or cortisol, nor would the size of the animal killed. However, if signalling male quality by 'showing off' was a larger relative driver of men's hunting behaviour, one would expect greater hormonal response in cases where men returned with large sharable kills, especially in the presence of community members. Consistent with provisioning models of male hunting motivation, neither kill size nor encountering an audience of villagers while returning from hunting was associated with hormonal changes for successful hunters. PMID:24335989
Trumble, Benjamin C; Smith, Eric A; O'Connor, Kathleen A; Kaplan, Hillard S; Gurven, Michael D
The present study investigated evening and nocturnal serum cortisol and melatonin concentrations in patients with primary insomnia to test if this clinical condition is accompanied by an increase of cortisol secretion and a simultaneous decrease of nocturnal melatonin production. Ten drug-free patients (4 males, 6 females) with primary insomnia (mean age+/-S.D.: 39.2+/-9.1 years) and 10 age- and gender-matched healthy controls participated in the study. All subjects spent three consecutive nights in the sleep laboratory with polysomnography. Measurement of cortisol and melatonin (from 19:00 h to 09:00 h) was performed prior to and during the last laboratory night. Contrary to expectation, cortisol secretion did not differ between healthy controls and insomniac patients. On the other hand, nocturnal melatonin production was significantly diminished in insomniac patients. Polysomnographically determined sleep patterns, in contrast to subjective ratings of sleep, demonstrated only minor alterations of sleep in the insomniac group. The lack of increased cortisol secretion in the patients with primary insomnia indicates that results from studies on the biological consequences of experimental sleep loss in healthy subjects cannot be applied to primary insomnia in general, especially if there are only minor objective sleep alterations. In spite of the negligible objective sleep disturbances in the present sample, nocturnal melatonin production was reduced, which tentatively suggests a role for this hormone in primary insomniacs. The pathophysiological significance of this finding is, however, still a matter of debate. PMID:12467942
Riemann, Dieter; Klein, Torsten; Rodenbeck, Andrea; Feige, Bernd; Horny, Andrea; Hummel, Ruth; Weske, Gesa; Al-Shajlawi, Anam; Voderholzer, Ulrich
At the core of anxiety disorders is the inability to use contextual information to modulate behavioral responses to potentially threatening events. Models of the pathogenesis of anxiety disorders incorporate stress and concomitant stress hormones as important vulnerability factors, while others emphasize sex as an important factor. However, translational basic research has not yet investigated the effects of stress hormones and sex on the ability to use contextual information to modulate responses to threat. Therefore, the purpose of the present study was threefold: first, we aimed at developing an experimental paradigm specifically capable of capturing contextual modulation of the expression of fear. Second, we tested whether cortisol would alter the contextualization of fear expression. Third, we aimed at assessing whether alterations in contextualization due to cortisol were different for men and women. Healthy participants (n = 42) received placebo or hydrocortisone (20 mg) prior to undergoing a newly developed differential contextual fear-conditioning paradigm. The results indicated that people rapidly acquire differential contextual modulation of the expression of fear, as measured by fear potentiated startle (FPS) and skin conductance responses (SCR). In addition, cortisol impaired the contextualization of fear expression leading to increased fear generalization on FPS data in women. The opposite pattern was found in men. Finally, as assessed by SCR, cortisol impaired differential conditioning in men. The results are in line with models suggesting heightened vulnerability in women for developing anxiety disorders after stressful events.
van Ast, Vanessa A.; Vervliet, Bram; Kindt, Merel
VARIOUS mechanisms have been proposed for the action of hormones in cells. One is a cytoplasmic mechanism involving mitochondria1,2; a second implies that cytoplasmic protein receptors act as sites3 for the hormone action; a third proposes that the nuclei act as a primary site for hormone action4,5. We now demonstrate that cortisol, when used for brief periods and in physiological
A. Maher Mansour; Sylvan Nass
Concentrations of parotid fluid cortisol and cortisone, and of plasma dialyzable cortisol, were measured in normal men before and 2 hours after treatment with 40 units of ACTH, and also before and after 10 days of receiving 5 mg. of diethylstilbestrol dai...
F. H. Katz I. L. Shannon
The steroid hormone cortisol has been associated with different levels of "stress" as well as different reproductive conditions in many primates. In callitrichids, cortisol has more often been reflective of female reproductive status than of chronic stress. In this study, we addressed the hypothesis that wild golden lion tamarin (Leontopithecus rosalia) females, whose social structure is characterized by low aggression and high social support, would not show rank ("stress")-related differences in glucocorticoids but would show reproductive changes. We collected 710 fecal samples from 22 adult females in Poço das Antas Reserve, Brazil, and nearby reintroduction areas, and assayed them for cortisol. Differences in cortisol levels were found between different reproductive conditions. Females in the first trimester of pregnancy had lower cortisol levels than nonpregnant females, although we did not differentiate between basal and ovulating levels in nonpregnant females. Cortisol rose in the third trimester of pregnancy. Primiparous females had a higher rise in the third trimester than multiparous females. No differences in cortisol levels were found among dominant females, ovulatory subordinate females, or anovulatory subordinate females. These results are similar to those obtained in other studies of callitrichid females. The lack of differences in cortisol excretion between dominants and subordinates is likely due to the low levels of overt aggression and the high level of social support available to subordinate females. PMID:16163718
Bales, Karen L; French, Jeffrey A; Hostetler, Caroline M; Dietz, James M
The "dual-hormone" hypothesis predicts that testosterone and cortisol will jointly regulate aggressive and socially dominant behavior in children and adults (e.g., Mehta & Josephs, 2010). The present study extends research on the dual-hormone hypothesis by testing the interaction between testosterone, cortisol, and personality disorder (PD) traits in predicting externalizing problems in a community sample of adolescent males and females. Participants were 106 youth from the community, ranging in age from 13-18 (Mage = 16.01 years, SDage = 1.29), and their parents. Parents and youth provided ratings on an omnibus measure of personality pathology and externalizing problems. Youth provided saliva samples via passive drool from which testosterone and cortisol levels were obtained. Robust moderation of the joint effects of testosterone and cortisol on parent-reported externalizing problems was found for both higher-order PD traits associated with externalizing psychopathology (Disagreeableness and Emotional Instability). Higher testosterone was associated with externalizing outcomes, but only when cortisol was low, and only among youth with high levels of Disagreeableness and Emotional Instability. These findings provide the first evidence for the dual-hormone hypothesis in a mixed-sex sample of community adolescents, but importantly offer novel evidence for the importance of personality traits. Examination of the joint regulation of externalizing problems by testosterone and cortisol in the context of adolescent personality may help to clarify inconsistent main effects of testosterone and cortisol on clinical externalizing phenotypes. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:24932763
Tackett, Jennifer L; Herzhoff, Kathrin; Harden, K Paige; Page-Gould, Elizabeth; Josephs, Robert A
Other papers in this special edition provide evidence to implicate activity of the limbic hypothalamic–pituitary–adrenocortical (L–HPA) system in the etiology of drug and alcohol abuse. Furthermore, studies in rodents and primates suggest that responsivity and regulation of this system later in life may be shaped by social experiences during early development. Cortisol is the major hormonal product of the L–HPA
Megan R. Gunnar; Bonny Donzella
The intensity of lymphocyte proliferation in response to pokeweed mitogen depends on cortisol level in the peripheral blood in the early post-traumatic period of penetrating eye injury. Lymphocyte proliferation in 72- and 96-h cultures from patients with high levels of endogenous hormone was suppressed. In 120-h cultures, the intensity of proliferation remains unchanged. Lymphocyte blast transformation was increased in 120-h cultures from patients with normal cortisol concentration and remained unchanged in case of low cortisol level. PMID:23113269
Chereshnev, V A; Shilov, Ju I; Gavrilova, T V; Usov, V V; Chereshneva, M V
One of the most commonly used stress biomarkers is cortisol, a glucocorticoid hormone released by the adrenal glands that is central to the physiological stress response. Free cortisol can be measured in saliva and has been the biomarker of choice in stress studies measuring the function of the hypothalamic-pituitary-adrenal axis. Chronic psychosocial stress can lead to dysregulation of hypothalamic-pituitary-adrenal axis function and results in an abnormal diurnal cortisol profile. Little is known about objectively measured stress and health in Latino populations in the United States, yet this is likely an important factor in understanding health disparities that exist between Latinos and whites. The present study was designed to measure cortisol profiles among Latino immigrant farmworkers in Oregon (USA), and to compare quantitative and qualitative measures of stress in this population. Our results indicate that there were no sex differences in average cortisol AUCg (area under the curve with respect to the ground) over two days (AvgAUCg; males?=?1.38, females?=?1.60; P?=?0.415). AUCg1 (Day 1 AUCg) and AvgAUCg were significantly negatively associated with age in men (P<0.05). AUCg1 was negatively associated with weight (P<0.05), waist circumference (P<0.01) and waist-to-stature ratio (P<0.05) in women, which is opposite of the expected relationship between cortisol and waist-to-stature ratio, possibly indicating hypothalamic-pituitary-adrenal axis dysregulation. Among men, more time in the United States and immigration to the United States at older ages predicted greater AvgAUCg. Among women, higher lifestyle incongruity was significantly related to greater AvgAUCg. Although preliminary, these results suggest that chronic psychosocial stress plays an important role in health risk in this population.
Previous work has found that many young children show different patterns of production of the hormone cortisol, which is sensitive to stress and challenge, on days when they are at child care compared with days when they are at home. At home, preschool age children typically show a decreasing pattern of cortisol production across the day which is…
Watamura, Sarah E.; Kryzer, Erin M.; Robertson, Steven S.
Background: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), patients demonstrate low levels of adrenal hormones. Objective: To investigate whether increased renal clearance and daily excretion contribute to this phenomenon. Methods: Thirty patients with RA, 32 with SLE, and 54 healthy subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17-hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEAS) were measured. Results: Clearance of DHEAS and DHEA was lower in patients than in HS, and clearance of androstenedione was somewhat higher in patients than in HS, but daily excretion of this latter hormone was low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups. The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was lower in patients than HS (but similar for cortisol). Serum DHEAS levels correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5–10 times more of this hormone than excreted by patients. Low serum levels of adrenal androgens and cortisol in patients as compared with HS were confirmed, and proteinuria was not associated with changes of measured renal parameters. Conclusions: This study in patients with RA and SLE demonstrates that low serum levels of adrenal androgens and cortisol are not due to increased renal clearance and daily loss of these hormones. Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE.
Straub, R; Weidler, C; Demmel, B; Herrmann, M; Kees, F; Schmidt, M; Scholmerich, J; Schedel, J
Ovariectomized rats were used in a model laboratory study to examine biochemical and pharmacodynamic effects of pre-gelatinized organic preparation of Lepidium peruvianum Chacon (Maca-GO). Biochemical and Pharmacodynamic effects of Maca-GO (250 mg Maca-GO per kg body weight (bw) administered by intubation twice daily) were assessed in a 28 day model laboratory study on ovariectomized (by laparoscopy) Wistar rats with pharmacodynamic tests performed at the conclusion of the trial followed by blood collection for morphology and biochemical tests. Toxicity of Maca-GO used in the study was determined in bioassay on mice and rats. Anti-depressive function (Porsolt’s test) and anxiolytic sedative and cognitive effects (using elevated-plus maze, locomotor activity and passive avoidance tests) were assessed against control (laparotomized female rats with intact ovaries). In addition to blood morphology, the following blood serum constituents were analyzed: Estrogen (E2), Progesterone (PGS), Cortisol (CT), Adrenocorticotropic Hormone (ACTH), Thyroid Hormones (TSH, T3, and T4), Iron (Fe) and lipid profile (Triglycerides, Total Cholesterol, LDL, HDL). Analytically-determined non-toxic status of Maca-GO was confirmed in bioassays when applied to mice and rats at levels of 0.5 and up to 15mg/kg bw which shows it safe use in humans with the LD50>15 mg/kg bw. Maca-GO showed a distinctive, (P<0.05) antidepressant-like and sedative effect in ovariectomized rats only, while there was no anxiolytic activity nor disturbance of cognitive function observed in both, test and control animals. Observed in this study balancing effect of Maca-GO on sex hormone levels show its potential as a safe preparation for use in correcting physiological symptoms characteristic in postmenopausal stage with an indication of potentially even more value for its use in pre-menopausal women.
Meissner, H. O.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Mscisz, A.; Kedzia, B.; Lowicka, A.; Reich-Bilinska, H.; Kapczynski, W.; Barchia, I.
The present study represents an attempt to define in greater detail the interrelationships between the concentration of cortisol, its binding by plasma protein and the renal mechanisms which appear to protect it from excessive loss. In normal subjects wit...
W. R. Beisel
Cortisol is a key hormone in the fish stress response with a well-known ability to regulate several physiological functions, including energy metabolism and the immune system. However, data concerning cortisol effects on fish innate immune system using a more controlled increase in cortisol levels isolated from any other stress related signaling is scarce. The present study describes the effect of doses of cortisol corresponding to acute and chronic levels on the complement and lysozyme activity in plasma of the rainbow trout (Oncorhynchus mykiss). We also evaluated the effects of these cortisol levels (from intraperitoneally implanted hydrocortisone) on the mRNA levels quantified by RT-qPCR of selected key immune-related genes in the liver, head kidney, and spleen. For that purpose, 60 specimens of rainbow trout were divided in to two groups: a control group injected with a coconut oil implant and another group injected with the same implant and cortisol (50??g cortisol/g body weight). Our results demonstrate the role of cortisol as a modulator of the innate immune response without the direct contribution of other stress axes. Our results also show a relationship between the complement and lysozyme activity in plasma and mRNA levels in liver, supporting the important role of this organ in producing these immune system proteins after a rise of cortisol in the fish plasma.
Cortes, R.; Teles, M.; Tridico, R.; Acerete, L.; Tort, L.
Evaluation of lipid and glucose metabolism and cortisol and thyroid hormone levels in obese appropriate for gestational age (AGA) born and non-obese small for gestational age (SGA) born prepubertal Slovak children.
Abstract Aim: Obesity is the major determinant of metabolic syndrome. Being born small for gestational age (SGA) may be co-responsible. We aimed at evaluating the association between 1. obesity and 2. being born SGA and the presence of endocrine-metabolic abnormalities in prepubertal Slovak children. Methods: The study included 98 children, aged 3-10.9 years: 36 AGA-born obese children (OB), 31 SGA-born children (SGA) and 31 appropriate for gestational age born non-obese children (AGA). Fasting serum levels of glucose, total cholesterol, LDL, HDL, triglycerides, fT4, TSH, cortisol and insulin were determined. HOMA-IR was calculated. Personal data about birth weight and length and family history were collected. Actual anthropometric measurement was done. Results: In every group, high prevalence of positive family history of metabolic disorder was found. In comparison with AGA children, OB children were taller (p<0.01) with higher body mass index (BMI) (p<0.001), and had increased insulin levels and homeostasis model assessment for insulin resistance (HOMA-IR) (p<0.001), decreased high-density lipoprotein (HDL) (p<0.001), and a trend to higher cortisol levels (p=0.069) was noted. SGA-born children were shorter (p<0.001), with BMI comparable to the AGA group. They had higher glucose levels (p<0.001), a trend to decreased HDL levels (p=0.085) and increased fT4 levels (p<0.001). A three-fold higher occurrence of metabolic abnormalities was present in obese children and twice more metabolic abnormalities were present in SGA-born children in comparison with AGA-born children. Conclusions: SGA-born children are more prone to developing endocrine-metabolic abnormalities than non-obese children born AGA, but they are at less risk than obese AGA-born children. We should provide specialized care for obese children already in prepubertal age and pay attention to SGA-born children. PMID:24706427
Blusková, Zuzana; Koštálová, Ludmila; Celec, Peter; Vitáriušová, Eva; Pribilincová, Zuzana; Maršálková, Marianna; Semberová, Jana; Kyselová, Tatiana; Hlavatá, Anna; Kovács, László
To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144±2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-3H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on ?-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., “stress hyperglycemia”) are a consequence of synergistic interactions among these hormones.
Eigler, Neal; Sacca, Luigi; Sherwin, Robert S.
Pacific salmon employ a semelparous reproductive strategy where sexual maturation is followed by rapid senescence and death. Cortisol overproduction has been implicated as the central physiologic event responsible for the post-spawning demise of these fish. Cortisol homeostasis is regulated through the action of hormones of the hypothalamus–pituitary–interrenal (HPI) axis. These include corticotropin-releasing factor (CRF) and urotensin-I (UI). In the present
Christian G. Westring; Hironori Ando; Takashi Kitahashi; Ramji Kumar Bhandari; Hiroshi Ueda; Akihisa Urano; Robert M. Dores; Anna A. Sher; Phillip B. Danielson
Although previous research has suggested cortisol-emotion relationships, little is known regarding the effect of anxiety type on cortisol levels or relationships between anxiety and longitudinal cortisol change in adolescents. The authors examine the differential relationship of cortisol levels with generalized and social anxiety and relationships…
Schiefelbein, Virginia L.; Susman, Elizabeth J.
Cortisol response to stress appears to differ between lactating and non-lactating animals. Lactating (14 d post partum) and non-lactating sheep were fitted with probes so that drugs and hormones could be infused directly into the posterior pituitary and paraventricular nucleus of the hypothalamus. The animals were also fitted with instruments to allow monitoring of heart rate, body temperature and blood cortisol levels. Their reactions to a source of acute stress (a barking dog) were then followed, with or without drug and hormone manipulation. Results in both lactating and non-lactating animals indicated shortcomings in the use of cortisol as a stress indicator. Infusing prolactin and oxytocin into either the posterior pituitary or the paraventricular nucleus of the hypothalamus suppressed cortisol responsiveness to stress in both lactating and non-lactating animals (the latter to a greater extent). In the absence of drugs, lactating animals had a slightly higher basal level of cortisol and a lower cortisol response to stress than their non-lactating counterparts. Despite suppression of cortisol responses, with or without drugs, other indicators of stress still changed with the presence of a barking dog, suggesting the complexity of control involved in stress responses. PMID:9275253
Cook, C J
In the classical theory of steroid hormone action, steroids diffuse through the membrane and alter transcription of specific genes resulting in synthesis of proteins important for modulating cell function. Most often, steroids work solely through the genome to exert their physiological actions in a process that normally takes hours or days to occur. In tilapia (Oreochromis mossambicus), cortisol inhibits prolactin
Russell J. Borski; Gregory N. Hyde; Shira Fruchtman; Wellington S. Tsai
This study was performed in order to establish the secretory patterns and the possible relationships between the adrenocorticotropin (ACTH)\\/cortisol and arginine vasopressin (AVP) responses in normal men to the systemic administration of ghrelin, an endogenous ligand for the growth hormone secretagogue receptor. For this purpose, a bolus of 1 ?g\\/kg ghrelin was injected intravenously in 9 normal men. AVP, ACTH
Vittorio Coiro; Gloria Saccani-Jotti; Roberta Minelli; Andrea Melani; Bruna Milli; Guido Manfredi; Riccardo Volpi; Paolo Chiodera
Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium
Navdeep Sandhu; Mathilakath M. Vijayan
Accumulating evidence suggests children enrolled in full-time child care often display afternoon elevations of the hormone cortisol, which is an indicator of stress. Recent advances in immunoassays allow for measurement of activity in the hypothalamic-pituitary-adrenal axis and the autonomic sympathetic nervous system from saliva, and measurement…
Hatfield, Bridget E.; Hestenes, Linda L.; Kintner-Duffy, Victoria L.; O'Brien, Marion
Two of the most salient physiological responses to stress are increased norepinephrine (NE) and cortisol (CORT) activities. However, it is unclear how these neurochemical events affect cognition, especially attention. We examined the effects of mild psychological stress on selective attention, as assessed by the negative priming (NP) paradigm. Salivary measures of the stress hormone CORT and ?-amylase (a correlate of
Patrick D Skosnik; Robert T Chatterton; Tara Swisher; Sohee Park
There has been a great deal of interest in the role of the neuroendocrine hormones of the hypothalamic-pituitary-adrenal (HPA) axis in the expression of stress-related psychopathology such as post-traumatic stress disorder (PTSD). This investigation examined the association of PTSD and childhood maltreatment with three key HPA axis hormones: cortisol, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). Regression analyses were undertaken on a sample of 43 participants with and 57 participants without PTSD. Results demonstrated that after controlling for age, sex, and PTSD status, exposure to childhood maltreatment was significantly associated with cortisol secretion [F(4,95)=11.68, ?R(2)=0.11, P=0.0009] and cortisol/DHEA ratio [F(4,95)=6.20, ?R(2)=0.05, P=0.01]. PTSD status was not associated with any of these neuroendocrine variables. Findings are discussed in the context of the complexity of the relationship of these neuroendocrine variables with trauma exposure and trauma-related psychopathology. It is suggested that DHEA(S) or cortisol/DHEA(S) ratios may not be biomarkers of specific forms of psychopathology per se, but that, instead, the severity and developmental timing of trauma may set the HPA axis in ways that are reflected in interactions among these neuroendocrine hormones. In adulthood, these HPA axis hormones may continue to be dynamically affected by personal and environmental resources. PMID:23907073
Van Voorhees, Elizabeth E; Dennis, Michelle F; Calhoun, Patrick S; Beckham, Jean C
Chronic elevation of glucocorticoid concentrations is detrimental to health. We investigated effects of chronic increase in plasma cortisol concentrations on energy balance and endocrine function in sheep. Because food intake and reproduction are regulated by photoperiod, we performed experiments in January (JAN) and August (AUG), when appetite drive is either high or low, respectively. Ovariectomized ewes were treated (intramuscularly) daily with 0.5mg Synacthen Depot(R) (synthetic adrenocorticotropin: ACTH) or saline for 4 wk. Blood samples were taken to measure plasma concentrations of cortisol, luteinising hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), leptin, insulin, and glucose. Adrenocorticotropin treatment increased concentrations of cortisol. During JAN, treatment reduced food intake transiently, but increased food intake in AUG. Leptin concentrations were reduced and glucose concentrations were greater in AUG, and insulin concentrations were similar throughout the year. Treatment with ACTH increased leptin concentrations in AUG only, whereas insulin concentrations increased in JAN only. Synacthen treatment increased glucose concentrations, with a greater effect in JAN. Changes in truncal adiposity and ACTH-induced cortisol secretion were positively correlated in JAN and negatively correlated in AUG. Treatment reduced the plasma LH pulse frequency in JAN and AUG, with an effect on pulse amplitude in JAN only. Treatment did not affect plasma GH or FSH concentrations. We conclude that chronically elevated cortisol concentrations can affect food intake, adiposity, and reproductive function. In sheep, effects of chronically elevated cortisol concentrations on energy balance and metabolism depend upon metabolic setpoint, determined by circannual rhythms. PMID:19733031
Henry, B A; Blache, D; Dunshea, F R; Clarke, I J
Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding ?1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases. PMID:25010111
Bolton, Jennifer L; Hayward, Caroline; Direk, Nese; Lewis, John G; Hammond, Geoffrey L; Hill, Lesley A; Anderson, Anna; Huffman, Jennifer; Wilson, James F; Campbell, Harry; Rudan, Igor; Wright, Alan; Hastie, Nicholas; Wild, Sarah H; Velders, Fleur P; Hofman, Albert; Uitterlinden, Andre G; Lahti, Jari; Räikkönen, Katri; Kajantie, Eero; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Kaakinen, Marika; Järvelin, Marjo-Riitta; Timpson, Nicholas J; Davey Smith, George; Ring, Susan M; Evans, David M; St Pourcain, Beate; Tanaka, Toshiko; Milaneschi, Yuri; Bandinelli, Stefania; Ferrucci, Luigi; van der Harst, Pim; Rosmalen, Judith G M; Bakker, Stephen J L; Verweij, Niek; Dullaart, Robin P F; Mahajan, Anubha; Lindgren, Cecilia M; Morris, Andrew; Lind, Lars; Ingelsson, Erik; Anderson, Laura N; Pennell, Craig E; Lye, Stephen J; Matthews, Stephen G; Eriksson, Joel; Mellstrom, Dan; Ohlsson, Claes; Price, Jackie F; Strachan, Mark W J; Reynolds, Rebecca M; Tiemeier, Henning; Walker, Brian R
Cortisol is a pleiotropic glucocorticoid hormone that acts through the intracellular glucocorticoid receptors (GR). Cortisol affects many important biological functions in mammals, including immune function, behavior, stress, metabolism, growth and organogenesis. In fishes, cortisol has an additional function in the osmoregulatory activity of ionocytes (ICs). Although much progress has been made toward understanding cortisol action at the levels of adult osmoregulatory tissues, the developmental functions of cortisol and its receptors in ICs remain to be clarified. We first analyzed the total contents of both cortisol and corticosteroid receptor mRNAs (GR1, GR2 and MR) during medaka development. Although low levels of cortisol were detected during development of the medaka embryo, maternal GR1, GR2 and MR transcripts were detected at higher levels than zygotic transcripts. We investigated the effect of exogenous cortisol on IC number during medaka embryogenesis. We observed that cortisol treatment induced an earlier expansion of the IC population but did not modify the final IC number. Using functional genomic approaches, we also tested the involvement of GR1, GR2 and mineralocorticoid receptor (MR) in IC development by systematic knock-down with translation-blocking morpholinos. Only GR2 knock-down led to a reduction of the total number of ICs in the epidermis. In addition, a GR2 splice-blocking morpholino did not have any effect on the biogenesis of ICs, underscoring the importance of maternally inherited GR2 mRNAs. We propose that maternal GR2, but not GR1 or MR, is a major pathway in the IC biogenesis in medaka most likely through cortisol activation, and that cortisol exposition fine-tunes their developmental timing. These findings provide a framework for future research on the regulatory functions of corticosteroids in euryhaline fishes and provide medaka as an advantageous model to further elucidate the underlying molecular regulatory mechanisms of IC development. PMID:24084592
Trayer, Vincent; Hwang, Pung-Pung; Prunet, Patrick; Thermes, Violette
Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30–60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding ?1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Direk, Nese; Lewis, John G.; Hammond, Geoffrey L.; Hill, Lesley A.; Anderson, Anna; Huffman, Jennifer; Wilson, James F.; Campbell, Harry; Rudan, Igor; Wright, Alan; Hastie, Nicholas; Wild, Sarah H.; Velders, Fleur P.; Hofman, Albert; Uitterlinden, Andre G.; Lahti, Jari; Raikkonen, Katri; Kajantie, Eero; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Kaakinen, Marika; Jarvelin, Marjo-Riitta; Timpson, Nicholas J.; Davey Smith, George; Ring, Susan M.; Evans, David M.; St Pourcain, Beate; Tanaka, Toshiko; Milaneschi, Yuri; Bandinelli, Stefania; Ferrucci, Luigi; van der Harst, Pim; Rosmalen, Judith G. M.; Bakker, Stephen J. L.; Verweij, Niek; Dullaart, Robin P. F.; Mahajan, Anubha; Lindgren, Cecilia M.; Morris, Andrew; Lind, Lars; Ingelsson, Erik; Anderson, Laura N.; Pennell, Craig E.; Lye, Stephen J.; Matthews, Stephen G.; Eriksson, Joel; Mellstrom, Dan; Ohlsson, Claes; Price, Jackie F.; Strachan, Mark W. J.; Reynolds, Rebecca M.; Tiemeier, Henning; Walker, Brian R.
Sex differences in incidence and severity of some stress-related, neuropsychiatric disorders are often reported to favor men, suggesting that women may be more vulnerable to aberrant hypothalamic-pituitary-adrenal (HPA) axis responses to stress. In this review, we discuss several investigations that we, and others, have conducted assessing salivary cortisol as a measure of HPA function. We have examined basal cortisol among healthy men and women and also following acute exposure to stressors. Among healthy participants, men had higher basal cortisol levels than did women. In response to acute stressors, such as carbon dioxide or noise, respectively, cortisol levels were comparable between men and women or higher among women. We have also examined cortisol levels among those with problem eating, gambling, or post traumatic stress disorder (PTSD). Women with restrained eating habits have higher basal cortisol levels than do women without restrained eating habits. Pathological gamblers have more aberrant stress response to gambling stimuli than do recreational gamblers, and these effects are more prominent among men than women. Men who have motor-vehicle accident related PTSD, demonstrate more aberrant cortisol function, than do their female counterparts. Although these sex differences in cortisol seem to vary with type of stress exposure and/or pathophysiological status of the individual, other hormones may influence cortisol response. To address this, cortisol levels among boys and girls with different stress-related experiences, will be the subject of future investigation.
Paris, Jason J.; Franco, Christine; Sodano, Ruthlyn; Freidenberg, Brian; Gordis, Elana; Anderson, Drew A.; Forsyth, John P.; Wulfert, Edelgard; Frye, Cheryl A.
Summary Background The dexamethasone/corticotropin releasing hormone (Dex/CRH) test has been proposed as a potential tool for identifying endophenotypes relevant to mood disorders. An exaggerated cortisol response to the test during major depressive episodes has been demonstrated for inpatients with melancholic or psychotic features. A diminished hormone response has been observed in chronically depressed outpatients. Methods Following a battery of self-report and interview assessments, 68 adults completed the Dex/CRH test. Thirty-four met structured interview criteria for current major depressive disorder and 34 age- and sex-matched control subjects had no current or lifetime DSM-IV depressive disorder. Effect of diagnosis on cortisol response to the Dex/CRH test was examined in a repeated measures general linear model. Results The matched groups were equivalent with regard to childhood adversity. Cortisol response to the Dex/CRH test among subjects with current MDD was not significantly different from that seen in matched healthy controls. Independent of diagnosis, an exploratory analysis showed a trend-level association between maltreatment history and diminished cortisol response; no interactive effects with depression diagnosis were detected. Conclusions The results do not support the hypothesis that elevated cortisol response to the Dex/CRH test represents a marker for major depressive episodes.
Carpenter, Linda L.; Ross, Nicole S.; Tyrka, Audrey R.; Anderson, George M.; Kelly, Megan; Price, Lawrence H.
Adrenal hormones regulate glucose levels, responses to unpredictable stressors and modulate cognition. Glucocorticoids can have an inverted-U shape relationship with cognition, as very low or high levels impair, whereas moderate elevations facilitate, acquisition and retention of memories. To date these relationships have been tested with humans and rodents in laboratory settings rather than with wild animals in biologically relevant contexts. This study examined whether the elevated cortisol observed in juvenile Belding's ground squirrels (Spermophilus beldingi) at natal emergence might promote both acquisition of adaptive responses to this species' two alarm calls warning of predators and memory of the spatial configuration of mothers' territories. Both experimentally increased and decreased basal cortisol levels interfere with acquisition and retention of an association between a warning call and the appropriate response compared with naturally occurring moderately elevated cortisol. Further, decreased cortisol impairs learning of a novel, complex spatial maze. Thus in the field the brief elevation of cortisol at emergence might facilitate acquisition of spatial memory of a three-dimensional environment and responses to alarm calls during a sensitive period of learning. This novel demonstration of the inverted-U shape function in a wild animal suggests that natural selection has favored a hormonal profile facilitating rapid acquisition of important survival behaviors.
Mateo, Jill M.
Sleep restriction alters hormone patterns and appetite in men, but less is known about effects on women. We assessed effects of overnight sleep restriction on cortisol and leptin levels and on appetite in young women. Participants' baseline sleep duration and eating habits were monitored for a week before the study. Salivary cortisol and leptin were sampled from fifteen healthy women (aged 18-25) during two consecutive days: first after a 10h overnight sleep opportunity (Baseline day) and then after a night including only 3h sleep (Post sleep-restriction day). Participants also completed appetite questionnaires on both days. Sleep restriction significantly reduced morning cortisol levels (p=0.02), elevated morning leptin levels (p=0.04), elevated afternoon/evening cortisol area under the curve values (p=0.008), and slowed the decline in cortisol concentration during the day (p=0.04). Hunger and craving scores did not differ significantly between days. A single night of restricted sleep affected cortisol rhythms and morning leptin levels in young women. PMID:20138072
Omisade, Antonina; Buxton, Orfeu M; Rusak, Benjamin
Chronic psychological stress is associated with accelerated aging, but the underlying biological mechanisms are not known. Prolonged elevations of the stress hormone cortisol is suspected to play a critical role. Through its actions, cortisol may potentially induce oxidatively generated damage to cellular constituents such as DNA and RNA, a phenomenon which has been implicated in aging processes. We investigated the relationship between 24 h excretion of urinary cortisol and markers of oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2?-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, in a sample of 220 elderly men and women (age 65 – 83 years). We found a robust association between the excretion of cortisol and the oxidation markers (R2?=?0.15, P<0.001 for both markers). Individuals in the highest quartile of cortisol excretion had a 57% and 61% higher median excretion of the DNA and RNA oxidation marker, respectively, than individuals in the lowest quartile. The finding adds support to the hypothesis that cortisol-induced damage to DNA/RNA is an explanatory factor in the complex relation between stress, aging and disease.
Joergensen, Anders; Broedbaek, Kasper; Weimann, Allan; Semba, Richard D.; Ferrucci, Luigi; Joergensen, Martin B.; Poulsen, Henrik E.
Background: Stress indicates the response or reaction of an organism to the environmental circumstances and their outcomes. Acute stress is well known to trigger several hormonal alterations in animals. An increase in glucocorticoid concentration can represent intensity of discomfort or distress experienced by an animal. The study was undertaken to evaluate the effects of various physical stress models on serum cortisol level in Wistar male rats. Methodology: In this study six Wistar male rats weighing 150-200 gm were randomly selected. Animals were exposed to ‘forced swim test’ and ‘restraint test’. Their serum cortisol level was measured by ELISA test using alpha prime ELISA system before and after the tests respectively. Results: Results were analyzed by students paired t-test. Serum cortisol level was significantly higher after forced swim test as well as after restraint test. When both the physical activities were compared, serum cortisol level was increased more after restraint stress than after forced swim test however, the difference was not significant statistically. Interpretation and Conclusion: The rise in serum cortisol level was observed in both the physical activity models . Rise in serum cortisol level was significantly higher after restraint test than exposing them to forced swim test. This indicates that restraining the rats produced more stress than making them forcefully swim.
Jameel, Mohammed Khaleel; Joshi, Anuradha Rajiv; Dawane, Jayashree; Padwal, Meghana; Joshi, AR; Pandit, V A; Melinkeri, RR
The impact of stress on health and disease is an important research topic in psychosomatic medicine. Because research on hypothalamic-pituitary-adrenal (HPA) axis regulation under controlled laboratory studies lacks ecological validity, it needs to be complemented by a research program that includes momentary ambulatory assessment. The measurement of salivary cortisol offers the possibility to trace the free steroid hormone concentrations in ambulant settings. Therefore, in this article, we first discuss the role of salivary cortisol in ambulatory monitoring. We start with a brief description of HPA axis regulation, and we then consider cortisol assessments in other organic materials, followed by a presentation of common salivary markers of HPA axis regulation suitable for ambulatory assessment. We further provide an overview on assessment designs and sources of variability within and between subjects (intervening variables), acknowledge the issue of (non)compliance, and address statistical aspects. We further give an overview of associations with psychosocial and health-related variables relevant for ambulatory assessment. Finally, we deal with preanalytical aspects of laboratory salivary cortisol analysis. The relative simplicity of salivary cortisol assessment protocols may lead to an overoptimistic view of the robustness of this method. We thus discuss several important issues related to the collection and storage of saliva samples and present empirical data on the stability of salivary cortisol measurements over time. PMID:22582339
Kudielka, Brigitte M; Gierens, Andrea; Hellhammer, Dirk H; Wüst, Stefan; Schlotz, Wolff
Objective: Hair analysis has been demonstrated to accurately reflect exposure to drug abuse, environmental toxins and exogenous hormones. We tested the feasibility of measuring cortisol and testosterone in hair of healthy and obese subjects. Measurements: A modified immunoassay (ELISA) originally developed for saliva was used. Hair, urine and blood samples were collected from young non-obese and obese patients. Perceived stress (PSS) was measured using a validated questionnaire. Results: There was no difference in PSS between non-obese and obese subjects. Hair cortisol levels were significantly correlated with weight (r=0.27, p<0.05) and systolic blood pressure (r=0.28, p<0.05), while the correlation with BMI did not reach statistical significance (p=0.063). Hair cortisol levels did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age (r=-0.47, p<0.05) and BMI (r=-0.40, p<0.05). The correlation between hair testosterone and free androgen index (FAI) did not reach statistical significance (p=0.098). The ratio of hair cortisol over hair testosterone (C/T) was higher in the obese group than in the young non-obese group. The C/T ratio correlated positively with age (r=0.56, p<0.01), waist circumference (r=0.63, p<0.01) and BMI (r=0.62, p<0.01), while the correlation between C/T ratio and FAI did not reach statistical significance. Conclusion: Hair cortisol levels increase, while hair testosterone levels decrease with obesity. The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone. As hair collection is non-invasive and is not influenced by moment-to-moment variations, the measurement of hormones in hair is a useful tool in research and possibly clinical practice. PMID:24941432
Chan, J; Sauvé, B; Tokmakejian, S; Koren, G; Van Uum, S
Relationships between cortisol responses to laboratory stress and cortisol output over the day have not been studied extensively. We tested associations between cortisol responses to a set of laboratory challenges (colour/word interference and mirror tracing) and three aspects of cortisol output over the day, namely total area under the curve (AUCday), the cortisol awakening response (CAR) and the slope of cortisol decline over the day. Participants were 466 men and women aged 54–76 years. We found that cortisol responses to laboratory stress were positively associated with cortisol AUCday independently of sex, age, socioeconomic status, smoking, body mass index, and time of laboratory testing (B = 0.212, 95% C.I. 0.143–0.282, p < 0.001). No associations between laboratory responses and the CAR or cortisol slope were observed. The laboratory–field association was not moderated by demographic or psychosocial factors. The study provides evidence for the ecological validity of acute laboratory stress testing.
Kidd, Tara; Carvalho, Livia A.; Steptoe, Andrew
1. Pancreatic endocrine function has been investigated in thyroidectomized calves given exogenous cortisol (2.0 mg.kg-1.day-1) in order to produce overt signs of diabetes. 2. Whenever this diabetic syndrome was induced it was associated with falling plasma insulin concentrations. A few days later, there was a significant rise in the post-absorptive concentration of both pancreatic glucagon and pancreatic polypeptide (PP) in the arterial plasma. Elevated levels of both hormones invariably persisted until the animals were given thyroxine. 3. Each of the pancreatic endocrine responses to cortisol was reversed by daily administration of thyroxine (25 microgram.kg-1. day-1) and the plasma glucose concentration was restored to normal within a few days. 4. Starvation was found to be an extremely effective way of reducing both the plasma glucose and glucagon concentration of diabetic calves without apparently affecting the concentration of either insulin of PP. 5. Neurally mediated release of insulin in response to 2-deoxyglucose, but not of either pancreatic glucagon or PP, was found to be defective in diabetic calves and recovered in response to thyroxine. 6. These results suggest that the primary defect that leads to the development of this diabetic syndrome in cortisol-treated thyroidectomized calves is failure of insulin release but that this is associated with consequential changes in the rates at which both glucagon and PP are released from the pancreas.
Bloom, S R; Edwards, A V; Fielding, A S
It has long been held that cortisol, acting through a single receptor, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. The recent finding that fish express a gene with high sequence similarity to the mammalian mineralocorticoid receptor (MR) suggests the possibility that a hormone other than cortisol carries out some mineralocorticoid functions in fish. To test for this
Stephen D. McCormick; Amy Regish; Michael F. O’Dea; J. Mark Shrimpton
PurposeThe neuropeptide, alpha-melanocyte stimulating hormone (?-MSH), is an endogenous antagonist of inflammation. Injections of ?-MSH peptide into inflamed tissues have been found to be very effective in suppressing autoimmune and endotoxin mediated diseases. We evaluated the potential to suppress ocular autoimmune disease (uveitis) by augmenting the expression of ?-MSH through subconjunctival injections of naked adrenocorticotropic hormone amino acids 1–17 (ACTH1–17)
D. J. Lee; D. J. Biros; A. W. Taylor
Sex steroids play major roles in vertebrate sexual differentiation. Unexpectedly, we now find that exposure to elevated levels of the naturally occurring stress hormone cortisol can also masculinize sexually dimorphic morphological characters and behaviour in adult female mosquitofish (Gambusia affinis) in a dose-dependent manner. Females masculinized by cortisol developed elongated anal fins with distal tip features similar to those of mature males. Most masculinized females also attempted to copulate when placed with normal females. Although the mechanism of masculinization is currently unknown, we propose a role for an enzyme that both inactivates cortisol and catalyzes the final step in synthesis of a major teleost androgen. This mechanism may also help explain some previously reported effects of stress on sexual development across vertebrate taxa. Our findings underscore the need to understand the full range of chemicals, both naturally occurring hormones and human-produced endocrine disruptors, that can influence sexual differentiation and reproductive function. PMID:20659923
Knapp, Rosemary; Marsh-Matthews, Edie; Vo, Luanne; Rosencrans, Sarah
Summary Baseline and TRH-induced changes of thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) were measured in 15 healthy control subjects and 63 psychiatric inpatients with DSM-III diagnoses of major depression (n = 19), schizophrenic disorder (n = 20), alcohol dependence (n = 10), and adjustment disorder (n = 14); baseline and postdexamethasone cortisol (CS) were also determined
Csaba M. Banki; Maria Vojnik; Mihaly Arato; Zsuzsa Papp; Zsuzsa Kovacs
Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs), we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI) and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.
Li, Yansong; Sescousse, Guillaume; Dreher, Jean-Claude
Recent data on various environmental stressors and blood hormone patterns are presented for lactating cattle. Known stressor effects of such factors as environ- mental temperature, air pollution, and noise on the plasma thyroxine, growth hormone, cortisol, prolactin, progester- one, luteinizing hormone, epinephrine, and norepinephrine of lactating cattle are discussed. Information on stressor effects is lacking on glucagon, insulin, vasopres- sin,
H. D. Johnson; W. J. Vanjonack
The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response. PMID:19135805
Cunningham-Bussel, Amy C; Root, James C; Butler, Tracy; Tuescher, Oliver; Pan, Hong; Epstein, Jane; Weisholtz, Daniel S; Pavony, Michelle; Silverman, Michael E; Goldstein, Martin S; Altemus, Margaret; Cloitre, Marylene; Ledoux, Joseph; McEwen, Bruce; Stern, Emily; Silbersweig, David
Objective Prior research has demonstrated that dieting, or the restriction of caloric intake, does not lead to long-term weight loss. This study tested the hypothesis that dieting is ineffective because it increases chronic psychological stress and cortisol production – two factors that are known to cause weight gain. Further, this study examined the respective roles of the two main behaviors that comprise dieting – monitoring one’s caloric intake and restricting one’s caloric intake – on psychological and biological stress indicators. Methods In a 2 (monitoring vs. not) × 2 (restricting vs. not) fully crossed, controlled experiment, 121 female participants were randomly assigned to one of four dietary interventions for three weeks. The monitoring + restricting condition tracked their caloric intake and restricted their caloric intake (1200 kcal/day); the monitoring only condition tracked their caloric intake but ate normally; the restricting only condition was provided 1200 kcal/day of food but did not track their calories, and the control group ate normally and did not track their intake. Before and after the interventions, participants completed measures of perceived stress and two days of diurnal saliva sampling to test for cortisol. Results Restricting calories increased the total output of cortisol, and monitoring calories increased perceived stress. Conclusions Dieting may be deleterious to psychological well-being and biological functioning, and changes in clinical recommendations may be in order.
Tomiyama, A. Janet; Mann, Traci; Vinas, Danielle; Hunger, Jeffrey M.; DeJager, Jill; Taylor, Shelley E.
The purpose of this study was to examine salivary cortisol, dehydroepiandrosterone (DHEA), and testosterone responses to the bench press in an international powerlifting competition and to determine whether these salivary hormone concentrations could be used to predict performance. Twenty-six elite athletes (13 females and 13 males) provided saliva samples during the official weighing-in and after the last attempt at the bench press, as well as at baseline on a non-competition day. Performance index was determined with the Wilks formula, which adjusts powerlifting scores according to body mass. Salivary cortisol concentrations were significantly increased in all subjects after the bench press (p < 0.01), whereas DHEA concentrations were significantly increased in women (p < 0.01) but not in men after the bench press. No significant change in testosterone concentrations was observed during the experiment in either men or women, which resulted in a marked decrease in the testosterone/cortisol ratio. The performance index showed no significant correlation with any of the hormone responses to competition. In conclusion, despite the increase in stress adrenocortical hormone responses to an international powerlifting competition, these hormone concentrations alone are not predictors of bench press performance in elite powerlifting athletes. PMID:20666655
Le Panse, B; Vibarel-Rebot, N; Parage, G; Albrings, D; Amiot, V; De Ceaurriz, J; Collomp, K
Background Stress and stress hormones modulate memory formation in various ways that are relevant to our understanding of stress-related psychopathology, such as posttraumatic stress disorder (PTSD). Particular relevance is attributed to efficient memory formation sustained by the hippocampus and parahippocampus. This process is thought to reduce the occurrence of intrusions and flashbacks following trauma, but may be negatively affected by acute stress. Moreover, recent evidence suggests that the efficiency of visuo-spatial processing and learning based on the hippocampal area is related to PTSD symptoms. Objective The current study investigated the effect of acute stress on spatial configuration learning using a spatial contextual cueing task (SCCT) known to heavily rely on structures in the parahippocampus. Method Acute stress was induced by subjecting participants (N = 34) to the Maastricht Acute Stress Test (MAST). Following a counterbalanced within-subject approach, the effects of stress and the ensuing hormonal (i.e., cortisol) activity on subsequent SCCT performance were compared to SCCT performance following a no-stress control condition. Results Acute stress did not impact SCCT learning overall, but opposing effects emerged for high versus low cortisol responders to the MAST. Learning scores following stress were reduced in low cortisol responders, while high cortisol-responding participants showed improved learning. Conclusions The effects of stress on spatial configuration learning were moderated by the magnitude of endogenous cortisol secretion. These findings suggest a possible mechanism by which cortisol responses serve an adaptive function during stress and trauma, and this may prove to be a promising route for future research in this area.
Meyer, Thomas; Smeets, Tom; Giesbrecht, Timo; Quaedflieg, Conny W. E. M.; Merckelbach, Harald
To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones. PMID:762240
Eigler, N; Saccà, L; Sherwin, R S
Glucocorticoid actions on the immune system are diverse and cell type dependent, and little is known about cell type-specific interactions and cross-talk between hormones and cytokines. In this study we have analyzed the gene expression patterns of the rainbow trout macrophage cell line RTS-11 by quantitative PCR, after exposure to combinations of cortisol plus a pro-inflammatory cytokine (e.g. recombinant trout IL-1?, IFN-?), type I IFN or a PAMP (LPS or poly I:C). Several key genes of the inflammatory process were targetted to assess whether any modulation of their expression occurred due to the addition of cortisol to this cell line. Incubation of macrophages for 3 or 6 h with a physiological concentration of cortisol caused a decrease in expression of IL-6 and IL-8, but no significant changes were observed for the other genes examined. Co-stimulation of cortisol with the inflammatory agents resulted in a general suppression of genes related to the inflammatory response. Cortisol inhibited the up-regulation of IL-8 by all the stimulants after 3 h of co-incubation. Suppression of the up-regulation of IL-6 by rIL-1?, rIFN-? and poly I:C, of ?IP by rIFN-? or poly I:C, and of Cox-2 by rIL-1? was seen after 6 h. In contrast, cortisol in combination with the pro-inflammatory agents has a synergistic effect on IL-10 expression, an anti-inflammatory molecule, suggesting that the activation of certain macrophage functions that lead to the resolution of inflammation occurs in fish macrophages in response to cortisol treatment. PMID:20965252
Castro, Rosario; Zou, Jun; Secombes, Christopher J; Martin, Samuel A M
In poikilothermic vertebrates, sex determination is sometimes influenced by environmental factors such as temperature. However, little is known about the molecular mechanisms underlying environmental sex determination. The medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. Recently, it was reported that XX medaka can be sex-reversed into phenotypic males by high water temperature (HT; 32-34 degrees C) treatment during the sex differentiation period. Here we report that cortisol caused female-to-male sex reversal and that metyrapone (an inhibitor of cortisol synthesis) inhibited HT-induced masculinization of XX medaka. HT treatment caused elevation of whole-body levels of cortisol, while metyrapone suppressed the elevation by HT treatment during sexual differentiation. Moreover, cortisol and 33 degrees C treatments inhibited female-type proliferation of germ cells as well as expression of follicle-stimulating hormone receptor (fshr) mRNA in XX medaka during sexual differentiation. These results strongly suggest that HT induces masculinization of XX medaka by elevation of cortisol level, which, in turn, causes suppression of germ cell proliferation and of fshr mRNA expression. PMID:20653000
Hayashi, Yuki; Kobira, Hiroshi; Yamaguchi, Toshiya; Shiraishi, Eri; Yazawa, Takashi; Hirai, Toshiaki; Kamei, Yasuhiro; Kitano, Takeshi
An ultrasensitive electrochemical immmunosensor was demonstrated to be capable of detecting the hormone cortisol down to concentrations as low as 16 pg mL(-1). In addition, the immunosensor displayed a sensitivity of 1.6 ?A pg(-1) mL(-1) and a linear range up to ?2500 pg mL(-1) of cortisol. This immunosensor was constructed based on a Au nanoparticle|dimethyl 3,3'-dithiobispropionimidate·2HCl (DTBP)-Protein G scaffold-modified Au electrode. In this work, the Au nanoparticles were used to increase the electrochemically active surface area by 28% (with a standard deviation of 3%) to enhance the quantity of the Protein G scaffold on the electrode. Thiolation of Protein G by DTBP aided in avoiding the confirmation change of Protein G, while this Protein G-DTBP component offered an orientation-controlled immobilisation of the capture antibody on the Au electrode. In this immunosensor, a monoclonal anti-cortisol capture antibody was optimally aligned by the scaffold before a competitive immunoassay between sample cortisol and a horseradish peroxidase-labelled cortisol conjugate was conducted. For quantitative analysis, square wave voltammetry was used to monitor the reduction current of benzoquinone produced from a horseradish peroxidase catalysed reaction. The improved analytical performance of our immunosensor was attributed to the synergetic effect of Au nanoparticles and the Protein G-DTBP scaffold. PMID:22005508
Liu, Xiaoqiang; Zhao, Ruoxia; Mao, Wenling; Feng, Heqing; Liu, Xiuhua; Wong, Danny K Y
Evidence suggests that patients with irritable bowel syndrome (IBS) are hyper-responsive to environmental, physical, and visceral stimuli. IBS patients also frequently report poor sleep quality. This study compared serum cortisol and plasma catecholamine levels during sleep between women with IBS (n = 30) and healthy controls (n = 31), and among subgroups within the IBS sample based on predominant stool patterns, IBS-diarrhea (n = 14), IBS-constipation (n = 7), and IBS-alternators (n = 9). Cortisol was measured from serial blood samples drawn every 20 minutes, and catecholamines every hour, in a sleep laboratory from 8 PM until awakening. Because of the varied sleep schedules of the individual participants, each subject’s hormone series time base was referenced with respect to their onset of Stage-2 sleep. Overall, there were no significant differences in cortisol or catecholamine patterns between women with IBS and controls, nor were there any group by time interactions. However, women with constipation-predominant IBS demonstrated significantly increased norepinephrine, epinephrine, and cortisol levels throughout the sleep interval, and women with diarrhea-predominant IBS were significantly lower on norepinephrine and cortisol. These results suggest that differences in neuroendocrine levels during sleep among IBS predominant bowel pattern subgroups may be greater than differences between IBS women and controls. Neuroendocrine profiles during sleep may contribute to our understanding of symptom expression in IBS.
Burr, Robert L.; Jarrett, Monica E.; Cain, Kevin C.; Jun, Sang-Eun; Heitkemper, Margaret M.
Pronounced circadian rhythms in numbers of circulating T cells reflect a systemic control of adaptive immunity whose mechanisms are obscure. Here, we show that circadian variations in T cell subpopulations in human blood are differentially regulated via release of cortisol and catecholamines. Within the CD4+ and CD8+ T cell subsets, naive cells show pronounced circadian rhythms with a daytime nadir, whereas (terminally differentiated) effector CD8+ T cell counts peak during daytime. Naive T cells were negatively correlated with cortisol rhythms, decreased after low-dose cortisol infusion, and showed highest expression of CXCR4, which was up-regulated by cortisol. Effector CD8+ T cells were positively correlated with epinephrine rhythms, increased after low-dose epinephrine infusion, and showed highest expression of ?-adrenergic and fractalkine receptors (CX3CR1). Daytime increases in cortisol via CXCR4 probably act to redistribute naive T cells to bone marrow, whereas daytime increases in catecholamines via ?-adrenoceptors and, possibly, a suppression of fractalkine signaling promote mobilization of effector CD8+ T cells from the marginal pool. Thus, activation of the major stress hormones during daytime favor immediate effector defense but diminish capabilities for initiating adaptive immune responses.
Dimitrov, Stoyan; Benedict, Christian; Heutling, Dennis; Westermann, Jurgen; Born, Jan
Background Several studies show an association between exposure to aircraft or road traffic noise and cardiovascular effects, which may be mediated by a noise-induced release of stress hormones. Objective Our objective was to assess saliva cortisol concentration in relation to exposure to aircraft noise. Method A multicenter cross-sectional study, HYENA (Hypertension and Exposure to Noise near Airports), comprising 4,861 persons was carried out in six European countries. In a subgroup of 439 study participants, selected to enhance the contrast in exposure to aircraft noise, saliva cortisol was assessed three times (morning, lunch, and evening) during 1 day. Results We observed an elevation of 6.07 nmol/L [95% confidence interval (CI), 2.32–9.81 nmol/L] in morning saliva cortisol level in women exposed to aircraft noise at an average 24-hr sound level (LAeq,24h) > 60 dB, compared with women exposed to LAeq,24h ? 50 dB, corresponding to an increase of 34%. Employment status appeared to modify the response. We found no association between noise exposure and saliva cortisol levels in men. Conclusions Our results suggest that exposure to aircraft noise increases morning saliva cortisol levels in women, which could be of relevance for noise-related cardiovascular effects.
Selander, Jenny; Bluhm, Gosta; Theorell, Tores; Pershagen, Goran; Babisch, Wolfgang; Seiffert, Ingeburg; Houthuijs, Danny; Breugelmans, Oscar; Vigna-Taglianti, Federica; Antoniotti, Maria Chiara; Velonakis, Emmanuel; Davou, Elli; Dudley, Marie-Louise; Jarup, Lars
Exposure of fish to stressors leads to multiple changes in the skin epithelium. We investigated the role of the stress hormone\\u000a cortisol in the control of these changes by exposure of pieces of skin from the rainbow trout Oncorhynchus mykiss with an in vitro tissue culture incubation procedure. The effects of 24 h exposure to 4 cortisol concentrations (0, 50, 500
A. L. van der Salm; D. T. Nolan; S. E. Wendelaar Bonga
Serum adrenal androgens (AAs), including androstenedione (?4A) and dehydroepiandrosterone sulfate (DHEAS), have been reported to be lower in female rheumatoid arthritis (RA) patients with early disease. Few data are available on hormonal status of women before the onset of clinical rheumatoid arthritis (pre-RA). A broad baseline panel of serum adrenal and sex steroids was compared in 36 female pre-RA to 144 matched cohort control (CN) subjects to determine differences in their mean values and in patterns of hormonal correlations. Study subjects having lower versus higher baseline serum cortisol levels than the total group's mean value were also analyzed separately to investigate differences in their hormonal levels and correlational patterns. In total subjects, mean (±SE) ?4A level (nmol/L) was lower (P = 0.018) in 28 pre-RA cases (6.4 ± 0.40) versus 108 CN (7.8 ± 0.28). The significant (P = 0.013) difference was restricted to 9 pre-RA versus 53?CN subjects having lower cortisol levels (5.6 ± 0.73 versus 8.0 ± 0.42?nmol/L, resp.). In total subjects, no significant difference was found between study subjects in their bivariate correlations of the hormonal panel variables, unlike results found in the subgroups stratified by lower versus higher cortisol levels. A subgroup of pre-RA females may have relative adrenal cortical insufficiency, as reflected by lower ?4A, especially observed among those subjects with lower cortisol levels.
Masi, Alfonse T.; Elmore, Kevin B.; Rehman, Azeem A.; Chatterton, Robert T.; Goertzen, Ned J.; Aldag, Jean C.
Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that has emerged as a critical mediator of endocrine function at multiple levels of the hypo- thalamic-pituitary-steroidogenic axis. Within the adrenal cortex, ACTH-dependent transcriptional responses, including transcriptional activation of several key steroidogenic enzymes within the ste- roid biosynthetic pathway, are largely dependent upon SF-1 action. The absence of a bona fide
Jonathon N. Winnay; Gary D. Hammer
Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair cortisol provides a simple way to monitor total cortisol release over an extended period of time. Hair cortisol levels were determined from each trimester (15, 26 and 36 wks gestation) and 3 months postpartum. Hair cortisol levels were compared to diurnal salivary cortisol collected over 3 days (3 times/day) at 14, 18, 23, 29, and 34 wks gestational age and 6 wks postpartum from 21 pregnant women. Both salivary and hair cortisol levels rose during pregnancy as expected. Hair cortisol and diurnal salivary cortisol area under the curve with respect to ground (AUCg) were also correlated throughout pregnancy. Levels of cortisol in hair are a valid and useful tool to measure long-term cortisol activity. Hair cortisol avoids methodological problems associated with collection other cortisol measures such as plasma, urine, or saliva and is a reliable metric of HPA activity throughout pregnancy reflecting total cortisol release over an extended period.
D'Anna-Hernandez, Kimberly L.; Ross, Randal G.; Natvig, Crystal L.; Laudenslager, Mark L.
Methods: Follicle stimulating hormone (FSH), luteinising hormone (LH), oestradiol, progesterone, prolactin, and cortisol concentrations in 63 women with FM were compared with those in 38 matched healthy controls; all subjects aged <35 years. The depression rate was assessed by the Beck Depression Inventory (BDI) and patients with high and low BDI scores were compared. Additionally, patients were divided according to sleep disturbance and fatigue and compared both with healthy controls and within the group. Results: No significant differences in FSH, LH, oestradiol, prolactin, and progesterone levels were found between patients with FM and controls, but cortisol levels were significantly lower in patients than in controls (p<0.05). Cortisol levels in patients with high BDI scores, fatigue, and sleep disturbance were significantly lower than in controls (p<0.05). Correlation between cortisol levels and number of tender points in all patients was significant (r = –0.32, p<0.05). Conclusion: Despite low cortisol concentrations in young women with FM, there is no abnormality in HPG axis hormones. Because fatigue, depression rate, sleep disturbance, and mean age of patients affect cortisol levels, these variables should be taken into account in future investigations.
Gur, A; Cevik, R; Sarac, A; Colpan, L; Em, S
An investigation was conducted to explore the relationship between acute changes in cortisol and memory and attention in the context of an acute naturalistic stressor, namely, examination stress. Sixty students (36 male, 24 female) participated in an assessment of self-reported levels of stress, salivary cortisol, short term memory, selective and divided attention and auditory verbal working memory. Assessments were conducted
K. Vedhara; J. Hyde; I. D. Gilchrist; M. Tytherleigh; S. Plummer
The current study explored the complicated interplay between aphasia and the stress biomarker, cortisol, in left hemisphere (LH) and right hemisphere (RH) stroke patients. Nineteen LH patients and 12 RH patients began the study between one to six months post-stroke and were followed for three months. During this time, language skills were assessed monthly while afternoon salivary cortisol samples were collected biweekly. The LH and RH groups showed improvements in language test scores over the course of three months; however, only naming skills in the RH group appeared to be associated with afternoon salivary cortisol levels. Furthermore, contradicting previous reports regarding laterality and cortisol regulation in humans, the current study found that both LH patients and RH patients exhibited similar afternoon salivary cortisol levels across all time points.
Laures-Gore, Jacqueline S.
Background: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of fetal testosterone concentrations. Aims: To investigate the relation between fetal testosterone and maternal and fetal cortisol. Methods: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15–38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations. Results: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes. Conclusion: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two.
Gitau, R; Adams, D; Fisk, N; Glover, V
The autonomic nervous system and circulating hormones control a stress reaction through a complex interaction. We tested the hypothesis that changes in cardiac vagal regulation may be positively associated with the serum testosterone-to-cortisol ratio during the first week of military service in 24 conscripts aged 19.0±0.3 years. Cardiac autonomic function was assessed by measuring high-frequency (HF: 0.15–0.4 Hz) and low-frequency
Jukka Huovinen; Mikko Tulppo; Juuso Nissilä; Vesa Linnamo; Keijo Häkkinen; Heikki Kyrolainen
Glucocorticoid actions on the immune system are diverse and cell type dependent, and little is known about cell type-specific interactions and cross-talk between hormones and cytokines. In this study we have analyzed the gene expression patterns of the rainbow trout macrophage cell line RTS-11 by quantitative PCR, after exposure to combinations of cortisol plus a pro-inflammatory cytokine (e.g. recombinant trout
Rosario Castro; Jun Zou; Christopher J. Secombes; Samuel A. M. Martin
Abnormal expression of membrane receptors has been previously described in benign adrenocortical neoplasms causing Cushing's syndrome. In particular, we have observed that, in some adreno corticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia tissues, cortisol secretion is controlled by ectopic serotonin7 (5-HT7) receptors. The objective of the present study was to investigate in vitro the effect of serotonin (5-hydroxy tryptamine; 5-HT) on
E Louiset; K Isvi; J M Gasc; C Duparc; B Cauliez; A Laquerriere; J M Kuhn; H Lefebvre
To examine the effect of intensive aerobic exercise on the interaction between endocrine and immune systems, we studied in ten normal healthy male subjects the effect of a 50-mile walking race on blood concentration of hormones (insulin, GH, ACTH, cortisol, adrenaline, noradrenaline, and dopamine), ketone bodies, specific immunological functions (IgG, IgM, and PHA\\/Con A-induced lymphocyte blastformation test), and nonspecific immune
Akira Fukatsu; Noriyuki Sato; Hiroyuki Shimizu
The stress system orchestrates brain and body responses to the environment. Cortisol (in humans) or corticosterone (in rodents) are important mediators of the stress system. Their action-in concert-is crucial for individual differences in coping with other individuals, which in turn depend on genetic- and experience-related factors. The actions exerted by cortisol and corticosterone have an enormous diversity. They include the regulation of rapid molecular aggregations, membrane processes, and gene transcription. In the latter transcriptional regulation, the corticosteroid hormones have two modes of operation. One mode is mediated by high-affinity mineralocorticoid receptors (MRs), which control gene networks underlying stabilization of neuronal activity as determinant for the sensitivity to trigger immediate responses to stress organized by corticotrophin-releasing hormone (CRH)-1 receptor. Whereas disturbance of homeostasis is prevented by MR-mediated processes, its recovery is facilitated via the low-affinity glucocorticoid receptors (GRs) that require stress levels of cortisol. GRs promote in coordination with CRH-2 receptors and the parasympathetic system behavioral adaptation and enhances storage of energy and information in preparation for future events. The balance in the two stress system modes is thought to be essential for cell homeostasis, mental performance, and health. Imbalance induced by genetic modification or stressors changes specific neural signaling pathways underlying cognition and emotion. This yin-yang concept in stress regulation is fundamental for genomic strategies to understand the mechanistic underpinning of corticosteroid-induced stress-related disorders such as severe forms of depression. PMID:15240347
De Kloet, E Ronald
Objectives: Some studies indicate that dentistry is one of the job categories with high potential exposure to elevated levels of extremely low frequency magnetic fields. In spite of this, information on occupational exposure of dentists to these fields is scarce. Studies on other common sources of electromagnetic fields (EMFs) such as mobile base stations have shown alterations in the cortisol level following exposure of humans to these sources. The aim of this study is to compare the level of cortisol among dentists and dentistry students who are being occupationally exposed to EMFs emitted by magnetostrictive cavitrons (case group) and among their counterparts who are not being exposed to these fields (control group). Materials and Methods: In this case–control study, blood samples were collected from 41 dentists and dentistry students, 21 of whom were exposed to EMFs emitted by cavitrons as the case group and 20 who were not exposed as the control group, twice; i.e. before work (at 8:30–9:30 a.m.) and after work (11:30–12:30 a.m.). The samples were coded and the serum cortisol level was investigated using the ELISA method (Cortisol AccuBind ELISA Kits). Results: The serum cortisol level of dentists and dental students in the morning (before starting the work) in the control group was 189.15 ± 110.70 (mean ± SD) whereas it was 157.77 ± 112.03 in those who were occupationally exposed to EMFs produced by the use of cavitrons. This difference was not statistically significant (P = 0.373). In contrast, the serum cortisol level of the participants in the noon (after stopping the work) in the control group was 136.25 ± 67.91 (mean ± SD) while it was 88.58 ± 52.83 in those who were occupationally exposed to EMFs produced by the use of cavitrons. This time, the observed difference was statistically significant (P = 0.016). In this light, while the difference between serum cortisol levels of dentists and dental students in the morning and after stopping the work was not statistically significant (P = 0.06), in the EMF-exposed group the cortisol level decreased significantly from 157.77 ± 112.03 in the morning to 88.58 ± 52.83 in the noon (P = 0.001). Conclusions: As far as we know, this is the first study that evaluated the effect of occupational exposure of dentists to EMFs on their serum cortisol level. The EMFs produced by magnetostrictive cavitrons can decrease the serum cortisol level in dentists. As cortisol plays an important role in blood pressure regulation, cardiovascular, and immune system function, a low cortisol level may threaten health. More studies are needed to clearly understand the effects of EMFs emitted by magnetostrictive cavitron on the level of stress hormones. As some studies have shown that exposure to EMFs has no effect on the cortisol level, whereas other studies reported either an increase or a decrease in the cortisol level, it can be concluded that the effects of exposure to EMFs may occur only at specific absorbed energies or energy absorption rates (usually known as window) similar to that exists in the case of exposure to the low doses of ionizing radiations.
Mortazavi, S. M. J.; Vazife-Doost, S.; Yaghooti, M.; Mehdizadeh, S.; Rajaie-Far, A.
It has been shown that cortisol concentrations change characteristically in the course of agonistic interactions; our aim was to find out how a playful situation may affect concentrations of this hormone in the saliva. We studied dogs' behavior and the changes of cortisol concentrations in a play situation, where the dogs played with their handler for 3 min with a tug toy. In this experiment working dogs were divided into two groups by the type of their work, namely police dogs and border guard dogs. We found that the cortisol concentrations of old police dogs significantly increased, while the adult border guard dogs' hormone levels decreased, which shows that playing with the handler has an effect on both groups, but interestingly this effect was opposite. Behavior analysis showed differences only in the behavior of the human handlers during the play sessions, while the behavior analysis did not reveal significant differences in the two groups of dogs, except that old border guard dogs generally needed more time to begin playing than old police dogs. During the play sessions police officers were mainly disciplining their dogs, while the border guards were truly playing with them (including affiliative and affectionate behavior). Our results are in accordance with those of recent studies, which show that behaviors associated with control, authority or aggression increase cortisol concentrations, while play and affiliative behavior decrease cortisol levels. PMID:18353328
Horváth, Zsuzsánna; Dóka, Antal; Miklósi, Adám
Objective Patients with end-stage renal disease (ESRD) can display the features of endogenous hypercortisolism but are difficult to evaluate for Cushing's syndrome. We evaluated the circadian rhythm of plasma compared with salivary cortisol in subjects with ESRD. Design Plasma and salivary cortisol and plasma ACTH samples were drawn frequently over 24?h in an inpatient research unit in stable ESRD subjects on daytime chronic hemodialysis (n=16) vs controls (n=8). Methods Plasma cortisol was measured every 2?h from 0800 to 0600?h the following day. Salivary cortisol was measured every 2?h, except between 2400 and 0400?h (sleep time). Plasma ACTH measured in a subset of samples and C-reactive protein (CRP) was measured as a marker of a subclinical inflammatory state in all subjects. Results ESRD subjects had a discernable circadian rhythm in plasma and salivary cortisol, but with a significantly higher nadir (1800–2400?h) compared with the controls (P=0.016–<0.001). After excluding four ESRD subjects without a normal circadian rhythm, the ESRD subjects still had higher nadir plasma and salivary cortisol and plasma ACTH compared with controls. There was no difference in the correlation of salivary and plasma cortisol in control vs ESRD subjects. ESRD subjects had higher CRP levels compared with controls. Conclusions ESRD subjects had increased late-night plasma and salivary cortisol and plasma ACTH levels. Late-night salivary cortisol is a reliable index of plasma cortisol in ESRD patients.
Raff, Hershel; Trivedi, Hariprasad
We report here on a longitudinal study of stress and women's reproduction in a small Kaqchikel Mayan community in rural Guatemala. Current understanding of the effects of stress on the reproductive axis in women is mostly derived from clinical studies of individual stressors. Little is known, however, about the cumulative effects of "real life" stress. Cortisol increases in response to a broad variety of individual stressors (Tilbrook et al., 2002). In this article, we evaluate the association between daily fluctuations in women's urinary cortisol and reproductive hormones: estrone conjugates (E(1)C), pregnandiol glucuronide (PdG), luteinizing hormone (LH), and follicle stimulating hormone (FSH). To assess the association between daily changes in cortisol levels and changes in the profiles of the reproductive hormones, we used a random coefficients model based on polynomial regression. The sample includes 92 menstrual cycles provided by 24 participants over a year-long prospective study. Increases in urinary cortisol levels were associated with significant increases in gonadotrophin and progestin levels during the follicular phase. Also, in a time window between days 4 and 10 after ovulation, increased cortisol levels were associated with significantly lower progestin levels. These results are significant because untimely increases in gonadotrophins and low midluteal progesterone levels have previously been reported to impinge on the ovulatory and luteinization processes and to reduce the chances of successful implantation (Ferin, 1999; Baird et al., 1999). Future research should consider the possibility that stress may affect fecundability and implantation without necessarily causing amenorrhoea or oligomenorrhoea. PMID:15368600
Nepomnaschy, Pablo A; Welch, Kathy; McConnell, Dan; Strassmann, Beverly I; England, Barry G
The overview of cortisol physiology, action and pathology is achieved in relation to the hypothalamic–pituitary–adrenal axis alteration by laboratory investigation. The measurements of cortisol and related compound levels in blood, urine and saliva used to study the physiological and pathological cortisol involvement, are critically reviewed. The immunoassay and chromatographic methods for cortisol measurement in the various biological fluids are examined
Rosalba Gatti; Giorgia Antonelli; Maddalena Prearo; Paolo Spinella; Enrico Cappellin; Elio F. De Palo
Cortisol has a well-documented circadian pattern. However, recent studies have demonstrated that individual variation in diurnal cortisol patterns occurs in young adult populations. Since older adults experience altered sleep–wake cycles and changes in circadian rhythmicity, we may see even greater variations in diurnal cortisol patterns in older adults. This study examined salivary cortisol patterns in 48 community dwelling older adults.
G. H Ice; A Katz-Stein; J Himes; R. L Kane
Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, p<05). Furthermore, with mediation analysis it was found that high cortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward sensitivity, and addictions. Future studies investigating effects of stress on reward sensitivity should take into account the severity of the stressor and the individual cortisol response to stress. PMID:24275010
Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen
Background Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system. Principal Findings We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) and electric stimulation stress. One hundred forty-nine healthy volunteers participated in this study. All subjects were exposed to both the TSST and electric stimulation stress on separate days. We measured sAA and salivary cortisol levels three times immediately before, immediately after, and 20 min after the stress challenge. The State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory test and the Profile of Mood State (POMS) tests were administered to participants before the electrical stimulation and TSST protocols. We also measured HF, LF and LF/HF Heart Rate Variability ratio immediately after electrical stimulation and TSST exposure. Following TSST exposure or electrical stimulation, sAA levels displayed a rapid increase and recovery, returning to baseline levels 20 min after the stress challenge. Salivary cortisol responses showed a delayed increase, which remained significantly elevated from baseline levels 20 min after the stress challenge. Analyses revealed no differences between men and women with regard to their sAA response to the challenges (TSST or electric stimulations), while we found significantly higher salivary cortisol responses to the TSST in females. We also found that younger subjects tended to display higher sAA activity. Salivary cortisol levels were significantly correlated with the strength of the applied electrical stimulation. Conclusions These preliminary results suggest that the HPA axis (but not the SAM system) may show differential response patterns to distinct kinds of stressors.
Maruyama, Yoshihiro; Kawano, Aimi; Okamoto, Shizuko; Ando, Tomoko; Ishitobi, Yoshinobu; Tanaka, Yoshihiro; Inoue, Ayako; Imanaga, Junko; Kanehisa, Masayuki; Higuma, Haruka; Ninomiya, Taiga; Tsuru, Jusen; Hanada, Hiroaki; Akiyoshi, Jotaro
Infectious pancreatic necrosis virus (IPNV) causes high incidence of disease in salmonids during the first period after SW transfer. During this period as well as during periods of stress, cortisol levels increase and indications of a relationship between IPNV susceptibility and cortisol have been suggested. The intestine is an entry route and a target tissue for IPNV displaying severe enteritis and sloughing of the mucosa in infected fish. The mechanisms behind effects of the virus on the intestinal tissue and the impact of cortisol on the effect remain unclear. In the present study, Atlantic salmon post smolts treated with or without slow release cortisol implants were subjected to a cohabitant IPNV challenge. Analysis of genes and proteins related to the innate and acquired immune responses against virus was performed 6 days post-challenge using qPCR and immunohistochemistry. An increased mRNA expression of anti-viral cytokine interferon type I was observed in the proximal intestine and head kidney as a response to the viral challenge and this effect was suppressed by cortisol. No effect was seen in the distal intestine. T-cell marker CD3 as well as MHC-I in both intestinal regions and in the head kidney was down regulated at the mRNA level. Number of CD8? lymphocytes decreased in the proximal intestine in response to cortisol. On the other hand, mRNA expression of Mx and IL-1? increased in the proximal intestine and head kidney in IPNV challenged fish in the presence of cortisol suggesting that the immune activation shifts in timing and response pathway during simulated stress. The present study clearly demonstrates that IPNV infection results in a differentiated epithelial immune response in the different intestinal regions of the Atlantic salmon. It also reveals that the epithelial immune response differs from the systemic, but that both are modulated by the stress hormone cortisol.
Niklasson, Lars; Sundh, Henrik; Olsen, Rolf-Erik; Jutfelt, Fredrik; Skj?dt, Karsten; Nilsen, Tom O.; Sundell, Kristina Snuttan
Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; p<0.001). Hence the regular use of Ecstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed. PMID:24333019
Parrott, A C; Sands, H R; Jones, L; Clow, A; Evans, P; Downey, L A; Stalder, T
The aim of this study was to determine whether preventing increases in plasma cortisol during antecedent hypoglycemia preserves autonomic nervous system counterregulatory responses during subsequent hypoglycemia. Experiments were carried out on 15 (8 male/7 female) healthy, overnight-fasted subjects and 8 (4 male/4 female) age- and weight-matched patients with primary adrenocortical failure. 5 d before a study, patients had their usual glucocorticoid therapy replaced with a continuous subcutaneous infusion of cortisol programmed to produce normal daily circadian levels. Both groups underwent identical 2-d experiments. On day 1, insulin was infused at a rate of 1.5 mU/kg per min, and 2-h clamped hypoglycemia (53+/-2 mg/dl) was obtained during the morning and afternoon. The next morning, subjects underwent an additional 2-h hypoglycemic (53+/-2 mg/ dl) hyperinsulinemic clamp. In controls, day 2 steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, growth hormone, and muscle sympathetic nerve activity were significantly blunted (P < 0.01) compared with day 1 hypoglycemia. In marked contrast, when increases of plasma cortisol were prevented in the patient group, day 2 neuroendocrine, muscle sympathetic nerve activity, hypoglycemic symptoms, and metabolic counterregulatory responses were equivalent with day 1 results. We conclude that (a) prevention of increases of cortisol during antecedent hypoglycemia preserves many critical autonomic nervous system counterregulatory responses to subsequent hypoglycemia; (b) hypoglycemia-induced increases in plasma cortisol levels are a major mechanism responsible for causing subsequent hypoglycemic counterregulatory failure; and (c) our results suggest that other mechanisms, apart from cortisol, do not play a major role in causing hypoglycemia-associated autonomic failure.
Davis, S N; Shavers, C; Davis, B; Costa, F
ContextCortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored.ObjectiveDetermination of the biological consequences of ultradian cortisol pulsatility.DesignA novel flow through cell culture system was developed to deliver ultradian pulsed or continuous cortisol to cells. The effects of cortisol dynamics on cell proliferation and survival, and on gene expression were determined.
Andrew McMaster; Maryam Jangani; Paula Sommer; Namshik Han; Andy Brass; Stephen Beesley; Weiqun Lu; Andrew Berry; Andrew Loudon; Rachelle Donn; David W. Ray; Jeffrey M. Gimble
In this study, we report evidence from sport competition that is consistent with the biosocial model of status and dominance. Results show that testosterone levels rise and drop following victory and defeat in badminton players of both sexes, although at lower circulating levels in women. After losing the match, peak cortisol levels are observed in both sexes and correlational analyses indicate that defeat leads to rises in cortisol as well as to drops in testosterone, the percent change in hormone levels being almost identical in both sexes. In conclusion, results show the same pattern of hormonal responses to victory and defeat in men and women. PMID:22429747
Jiménez, Manuel; Aguilar, Raúl; Alvero-Cruz, José R
To examine the effects of sustained (48-hour) hypoxemia on fetal and maternal adrenocorticotropic hormone concentrations and on maternal progesterone, uterine blood flow was reduced in eight sheep at day 128 of pregnancy by means of an adjustable Teflon clamp placed around the maternal common internal iliac artery. Control measurements were made in four animals in which the vascular clamp was not adjusted. Fetal PaO2 fell from 20.6 +/- 1.1 mm Hg (mean +/- SEM) to 16.6 +/- 0.6 mm Hg within 1 hour after application of the clamp and remained suppressed during 48 hours. There was a transient acidemia at 1 to 2 hours that had corrected by 8 hours. Fetal adrenocorticotropic hormone levels rose from 24 +/- 6 to 1320 +/- 205 pg/ml at 2 hours but decreased by 16 hours. Measured by high-pressure liquid chromatography, more than 95% of immunoreactivity corresponded to adrenocorticotropic hormone1-39. Fetal cortisol levels rose by 6 hours and remained elevated through 48 hours. Maternal adrenocorticotropic hormone, cortisol, and progesterone levels were unchanged during the study period. We conclude that fetal hypoxemia-acidemia after restriction of uterine blood flow provokes fetal adrenocorticotropic hormone release, but the elevation in adrenocorticotropic hormone is not sustained. However, the level of fetal cortisol rises progressively, consistent with fetal adrenal activation. PMID:2540657
Challis, J R; Fraher, L; Oosterhuis, J; White, S E; Bocking, A D
The thyroid-stimulating hormone (TSH) is a pituitary glycoprotein hormone that controls the synthesis and secretion of thyroid hormones. TSH secretion is primarily regulated by the negative feedback mechanism of circulating thyroid hormones and by the stimulatory activity of a hypothalamic factor, the thyrotropin-releasing hormone (TRH). Recent advances consist mainly of a better understanding of the TSH receptor which is involved
P. Beck-Peccoz; M. Bonomi; L. Persani
Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids. ?? 2005 Elsevier Inc. All rights reserved.
Sakamoto, T.; McCormick, S. D.
Relationships between cortisol responses to laboratory stress and cortisol output over the day have not been studied extensively. We tested associations between cortisol responses to a set of laboratory challenges (colour/word interference and mirror tracing) and three aspects of cortisol output over the day, namely total area under the curve (AUCday), the cortisol awakening response (CAR) and the slope of cortisol decline over the day. Participants were 466 men and women aged 54-76 years. We found that cortisol responses to laboratory stress were positively associated with cortisol AUCday independently of sex, age, socioeconomic status, smoking, body mass index, and time of laboratory testing (B=0.212, 95% C.I. 0.143-0.282, p<0.001). No associations between laboratory responses and the CAR or cortisol slope were observed. The laboratory-field association was not moderated by demographic or psychosocial factors. The study provides evidence for the ecological validity of acute laboratory stress testing. PMID:24582772
Kidd, Tara; Carvalho, Livia A; Steptoe, Andrew
Pregnancy anxiety is a potent predictor of adverse birth and infant outcomes. The goal of the current study was to examine one potential mechanism whereby these effects may occur by testing associations between pregnancy anxiety and maternal salivary cortisol on 4 occasions during pregnancy in a sample of 448 women. Higher mean levels of pregnancy anxiety over the course of pregnancy predicted steeper increases in cortisol trajectories compared to lower pregnancy anxiety. Significant differences between cortisol trajectories emerged between 30 and 31 weeks of gestation. Results remained significant when adjusted for state anxiety and perceived stress. Neither changes in pregnancy anxiety over gestation, nor pregnancy anxiety specific to only a particular time in pregnancy predicted cortisol. These findings provide support for one way in which pregnancy anxiety may influence maternal physiology and contribute to a growing literature on the complex biological pathways linking pregnancy anxiety to birth and infant outcomes. PMID:24769094
Kane, Heidi S; Dunkel Schetter, Christine; Glynn, Laura M; Hobel, Calvin J; Sandman, Curt A
... therapy, they may increase the risks of serious medical conditions. There also is a risk of drug interactions and side effects. Bioidentical Hormones Bioidentical hormones are hormones manufactured from plants that are combined together (compounded) by a pharmacist ...
Cortisol is a biomarker of stress reactivity, and its diurnal pattern is an indicator of general neuroendocrine health. Despite theories conceptualizing marital dyads as dynamic systems wherein spouses are interdependent in their physiology and stress coping, little is known about the daily processes in which spouses possibly influence each other in biological stress. Nineteen heterosexual couples provided saliva samples containing cortisol 4 times a day for 4 consecutive days. We used multilevel modeling to examine whether one's cortisol awaking response (CAR) and diurnal cortisol slope (DCS) predict those of the spouse's on the same day and/or on the next day. We found that spouses synchronize their DCS, such that on days when one experiences faster or slower decline in diurnal cortisol than usual, the spouse also experiences faster or slower decline than usual. For CAR, positive synchrony was only observed in couples reporting high levels of marital strain and disagreement. Cross-lagged regression analysis reveals stability in diurnal cortisol pattern. A steeper cortisol slope on a particular day predicts a steeper slope on the next day within an individual, but no significant cross-lagged relation was found between spouses. Couples reporting more spousal support tend to have stronger stability in CAR. These findings provide evidence that spouses are interdependent in their diurnal cortisol patterns on a day-to-day basis, and that these daily dynamics are associated with marital relationship quality. The study contributes to our understanding of marital processes and biobehavioral health. It also contributes methodologically to the advancement of longitudinal dyadic analysis. PMID:23978320
Liu, Siwei; Rovine, Michael J; Klein, Laura Cousino; Almeida, David M
Basal plasma cortisol levels in 12 controls and 60 patients with different types of leprosy were within normal limits. They were significantly lower in multibacillary leprosy patients; this abnormality might be due to long standing stress leading to adrenal exhaustion. The plasma cortisol level significantly increased after the ACTH (Synacthen) stimulation test in all of the varieties of leprosy tested, which suggests that the adrenal reserve is maintained in such cases. PMID:7722095
Bansal, R; Garg, B R; Adithan, C; Vasireddi, S S; Kumar, V; Chandra, D
The stress hormone cortisol is the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and the cortisol awakening response (CAR) refers to the rapid rise in cortisol levels observed immediately following awakening. During the CAR period, cortisol levels typically increase by 38%-75%, peaking approximately 30 min after awakening. Evidence suggests the function of the CAR may be related to arousal, energy boost and/or anticipation, although its precise function is still unknown. The CAR has been investigated in a range of clinical populations including the assessment of daytime dysfunction in insomnia; however little research, if any, has specifically examined its relation to sleep architecture, or night-time difficulties associated with insomnia. The aim of this review is to provide an overview of the CAR, a description of the factors which can affect it, and to outline the CAR in relation to the '3P' model of insomnia. This review concludes with a description of a standard protocol for measurement of the CAR, which can be adapted and applied within sleep medicine. PMID:23835138
Elder, Greg J; Wetherell, Mark A; Barclay, Nicola L; Ellis, Jason G
The aim of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis activity of Holstein-Friesian and crossbreed F1 heifers by analysis of the cortisol concentrations in hair samples. Cortisol, the primary hormone of the HPA axis, is the biological endpoint for the investigation of the HPA response. The study was conducted on 290 prepubertal heifers; 142 heifers were pure Holstein-Friesian and 148 were crossbreed F1 heifers obtained from the 3-way rotational system with Swedish Red and Montbéliarde breeds. Extraction was performed on the hair using methanol, and cortisol concentrations were determined by a radioimmunoassay method. Cortisol concentrations measured in regrown hair of crossbreed F1 heifers were significantly lower than those in hair of Holstein-Friesian heifers. This result helps us to better understand the differences in HPA activity and allostatic load between Holstein-Friesian and crossbreed F1 heifers and allows us to better assess the adaptability of these animals to the environment and the importance of crossbreed traits for profitability in dairy farming. PMID:23522680
Peric, T; Comin, A; Corazzin, M; Montillo, M; Cappa, A; Campanile, G; Prandi, A
To examine the effect of intensive aerobic exercise on the interaction between endocrine and immune systems, we studied in ten normal healthy male subjects the effect of a 50-mile walking race on blood concentration of hormones (insulin, GH, ACTH, cortisol, adrenaline, noradrenaline, and dopamine), ketone bodies, specific immunological functions (IgG, IgM, and PHA/Con A-induced lymphocyte blastformation test), and nonspecific immune (CH50, and neutrophil bactericidal functions). Neutrophil bactericidal activity was measured as chemiluminescences amplified by luciferin analog (CLA-DCL) and luminol (L-DCL). The race increased cortisol and ketone bodies, and decreased insulin, CLA-DCL, and L-DCL (all parameters; P < 0.01). However, other parameters were not significantly changed. There were significant negative correlations between changes of ketone bodies/cortisol and CLA/L-DCL (P < 0.05), however there was no significant correlations between changes of insulin and CLA/L-DCL. These data indicate that extensive aerobic exercise causes impaired neutrophil bactericidal function, probably due to the induced increases in both cortisol and ketone bodies. This impaired neutrophil function may cause the susceptibility to infection after an extensive exercise. PMID:8649223
Fukatsu, A; Sato, N; Shimizu, H
Background The dexamethasone/corticotropin releasing hormone (Dex/CRH) test has been proposed as a potential tool for identifying endophenotypes relevant to mood disorders. Several studies have shown abnormal cortisol reactivity in phenotypically healthy adults without psychiatric disorders as a function of exposure to adverse early environments. Methods Following a battery of self-report and interview assessments, 230 adults without major Axis I Disorders completed the Dex/CRH test. Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). Effect of childhood emotional abuse (EA) on cortisol responses to the Dex/CRH test was examined with repeated measures general linear models including age, sex and other types of maltreatment. Post-hoc models examined the significant interaction between EA and age, and tested the stability of the main findings with selected covariates. Results A history of self-reported childhood EA independently and significantly diminished cortisol response. This effect was amplified with advancing subject age, and was independent of the effects of other types of childhood maltreatment, lifetime diagnoses, and symptom scores. Conclusions Dampened cortisol reactivity may be a consequence of childhood emotional abuse that is cumulative over time. Prospective longitudinal investigation is needed to evaluate the potential of this proposed endophenotype.
Carpenter, Linda L.; Tyrka, Audrey R.; Ross, Nicole S.; Khoury, Lamya; Anderson, George M.; Price, Lawrence H.
As inherently social animals, humans are very sensitive to behavioral signals from other members of their group. Nonconscious imitation of conspecifics' behavior (also called social mirroring) is a common manner in which people express their sense of similarity and affiliation with others. This evolutionary important behavioral repertoire has been referred to as 'social glue' as it cultivates pro-social behaviors that foster one's acceptance by the group as well as sustain societal unity. Lack of behavior imitation therefore serves a subtle cue signaling rejection by others. Because being rejected is a stressful experience that is known to raise cortisol levels in humans and other primates such as baboons, we reasoned that not being imitated by another person during an interpersonal interaction may enhance cortisol levels as an acute physiological stress reaction to the behavioral rejection signal by their conspecifics. In the present study, female participants were unobtrusively imitated or not imitated by another person. None of the participants indicated awareness of (not) being imitated. The salivary cortisol concentrations of not imitated participants did not differ from those of the imitated participants on a baseline measurement, but they increased considerably after the interaction, whereas the cortisol level of imitated participants remained stationary. This stressful consequence of a lack of behavioral imitation was mediated by self-reported need to belong. These findings provide new insights into the impact of a lack of behavioral imitation on the receiver's hormonal secretion and its functionality in social interactions. PMID:20109459
Kouzakova, Marina; van Baaren, Rick; van Knippenberg, Ad
Intracellular zinc signaling is important in the control of a number of cellular processes. Hormonal factors that regulate cellular zinc influx and initiate zinc signals are poorly understood. The present study investigates the possibility for cross talk between the glucocorticoid and zinc signaling pathways in cultured rainbow trout gill epithelial cells. The rainbow trout metallothionein A (MTA) gene possesses a putative glucocorticoid response element and multiple metal response elements 1042 base pairs upstream of the start codon, whereas metallothionein B (MTB) and zinc transporter-1 (ZnT1) have multiple metal response elements but no glucocorticoid response elements in this region. Cortisol increased MTA, MTB, and ZnT1 gene expression, and this stimulation was enhanced if cells were treated with cortisol together with zinc. Cells treated with zinc showed increased zinc accumulation, transepithelial zinc influx (apical to basolateral), and intracellular labile zinc concentrations. These responses were also significantly enhanced in cells pretreated with cortisol and zinc. The cortisol-mediated effects were blocked by the glucocorticoid receptor (GR) antagonist RU-486, indicating mediation via a GR. In reporter gene assays, zinc stimulated MTA promoter activity, whereas cortisol did not. Furthermore, cortisol significantly reduced zinc-stimulated MTA promoter activity in cells expressing exogenous rainbow trout GR. These results demonstrate that cortisol enhances cellular zinc uptake, which in turn stimulates expression of MTA, MTB, and ZnT1 genes. PMID:18077514
Bury, Nic R; Chung, Mi Ja; Sturm, Armin; Walker, Paul A; Hogstrand, Christer
Little is known about the impact of stress and stress hormones on the processing of visceral-afferent signals. Clinical data suggest that cortisol may lower the threshold for interoceptive stimuli, while a pharmacological administration of cortisol decreases the sensitivity for physical symptoms. To clarify the role of cortisol for the processing of interoceptive signals, we investigated 16 healthy men on two occasions, once during the infusion of 4 mg of cortisol and once during the infusion of a placebo substance. Heartbeat-evoked potentials (HEP; derived from resting EEG and ECG, during open and closed eyes), which are psychophysiological indicators for the cortical processing of cardioceptive signals, were measured over 6-min periods once before, and four times after the infusion (1-7, 11-17, 21-27 and 31-37 min). We found that HEP amplitudes were higher during open than during closed eyes between 1 and 17 min after cortisol infusion. There was no effect of cortisol on heart rate. We conclude that cortisol may rapidly modulate the cortical processing of cardioceptive neural signals. These results may have relevance for the effects of stress on the development and maintenance of psychosomatic symptoms. PMID:23850227
Schulz, André; Strelzyk, Florian; Ferreira de Sá, Diana S; Naumann, Ewald; Vögele, Claus; Schächinger, Hartmut
Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. We report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery. Images
Robinson, B G; Emanuel, R L; Frim, D M; Majzoub, J A
Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ? 0.03), as was ACTH-cortisol cross-approximate entropy (P ? 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590
Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J; Veldhuis, Johannes D; Van den Berghe, Greet
Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ? 0.03), as was ACTH-cortisol cross-approximate entropy (P ? 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness.
Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guiza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.
The history of the studies on stress and hormones is briefly reviewed. The two main stress transmission systems are the endocrine (CRH-ACTH-Cortisol) and the neural (Sympatho-adreno-medullary) systems. The junction of the two systems resides in the hypothalamus. It has been clarified that CRH has central suppressive effects on eating, sleeping and sexual behavior. The relationships between emotions such as fear, anger and neurotransmitters (noradrenaline or serotonin) are discussed. Recent studies have revealed that various kinds of cytokines secreted from leukocytes stimulate the secretions of CRH and ACTH. Thus the cooperative mechanisms and actions of the endocrine, neural and immune systems against stress to keep homeostasis are elucidated. PMID:7958098
Background\\/Aims: No studies have clearly demonstrated how sex hormones are involved in the observed gender difference in growth and plasma cholesterol levels in animals fed hypercholesterolemic diets. This study was conducted to determine the effects of gender, gonadectomy (GNX), and sex hormones on growth, plasma cholesterol and cortisol levels in Sprague-Dawley rats. Methods: In the first of two experiments, equal
Chong-Eon Lee; Jung-Suk Kang; Kyu-Il Kim
Emotionally arousing material is typically better remembered than neutral material. Since norepinephrine and cortisol interact to modulate emotional memory, sex-related influences on stress responses may be related to sex differences in emotional memory. Two groups of healthy women – one naturally cycling (NC women, N = 42) and one using hormonal contraceptives (HC women, N = 36) – viewed emotionally arousing and neutral images. Immediately after, they were assigned to Cold Pressor Stress (CPS) or a control procedure. One week later, participants received a surprise free recall test. Saliva samples were collected and later assayed for salivary alpha-amylase (biomarker for norepinephrine) and cortisol. Compared to NC women, HC women exhibited significantly blunted stress hormone responses to the images and CPS. Recall of emotional images differed between HC and NC women depending on noradrenergic and cortisol responses. These findings may have important implications for understanding the neurobiology of emotional memory disorders, especially those that disproportionately affect women.
Nielsen, Shawn E.; Segal, Sabrina K.; Worden, Ian V.; Yim, Ilona S.; Cahill, Larry
Recent studies suggest that facial attractiveness indicates immune responsiveness in men and that this relationship is moderated by stress hormones which interact with testosterone levels. However, studies testing whether facial attractiveness in women signals their immune responsiveness are lacking. Here, we photographed young Latvian women, vaccinated them against hepatitis B and measured the amount of specific antibodies produced, cortisol levels and percentage body fat. Latvian men rated the attractiveness of the women's faces. Interestingly, in women, immune responsiveness (amount of antibodies produced) did not predict facial attractiveness. Instead, plasma cortisol level was negatively associated with attractiveness, indicating that stressed women look less attractive. Fat percentage was curvilinearly associated with facial attractiveness, indicating that being too thin or too fat reduces attractiveness. Our study suggests that in contrast to men, facial attractiveness in women does not indicate immune responsiveness against hepatitis B, but is associated with two other aspects of long-term health and fertility: circulating levels of the stress hormone cortisol and percentage body fat. PMID:23697641
Rantala, Markus J; Coetzee, Vinet; Moore, Fhionna R; Skrinda, Ilona; Kecko, Sanita; Krama, Tatjana; Kivleniece, Inese; Krams, Indrikis
In embryonic neural retina the enzyme glutamine synthetase [GS; L-glutamate:ammonia ligase (ADP-forming), EC 18.104.22.168] is a glia-specific differentiation marker inducible with cortisol. We show that cortisol elicits GS mRNA accumulation by stimulating transcription of the GS gene and that this stimulation requires cell contacts: in dissociated and separated retina cells GS gene transcription was not induced; when the separated cells were reassembled into multicellular aggregates, restoring cell contacts, accumulation of GS mRNA was again inducible. In cells dissociated from retina tissue that had been preinduced with cortisol, GS gene transcription rapidly declined, despite continued hormone availability. In the separated cells transcription of the histone H3.3 gene and accumulation of carbonic anhydrase II mRNA were unaffected; therefore, cell separation selectively precluded induction of the GS gene. These findings provide direct evidence for the regulatory role of cell contacts in hormonal control of gene transcription. Images
Vardimon, L; Fox, L L; Degenstein, L; Moscona, A A
Summary To evaluate the relative role of diabetogenic hormones as insulin antagonists in severe derangements of diabetic control, glucagon, cortisol, growth hormone and adrenaline were administered by continuous intravenous infusion, separately and in combination, to ketosis-prone insulin-dependent diabetics (n=11). The amount of insulin required for the assimilation of a 50 g glucose load during the various hormone infusions was determined by
P. Bratusch-Marrain; B. Grubeck-Loebenstein; A. Korn; H. Vierhapper; P. Nowotny
A cross-sectional study examined whether there was a difference in endogenous serum sex hormone levels between community-dwell- ing postmenopausal women with Alzheimer's disease (AD) and healthy controls. Total morning levels of serum estrone, estradiol, androstenedione, testosterone, and cortisol were measured in 52 non- depressed women with AD and 60 postmenopausal women who were neither depressed nor cognitively impaired. Estradiol was
C. J. CUNNINGHAM; M. SINNOTT; A. DENIHAN; M. ROWAN; J. B. WALSH; R. O'MOORE; D. COAKLEY; R. F. COEN; B. A. LAWLER; D. D. O'NEILL
Purpose This study investigated whether hormones and pain perception are associated with exam anxiety, and also whether exam anxiety is affected by seasonal differences in testosterone and cortisol levels. Materials and Methods Forty-six healthy males were recruited from a medical college. Anxiety was induced by having participants perform the Objective Structured Clinical Examination. Pressure was applied to the participants to induce pain. Pain thresholds, pain ratings, anxiety ratings, blood pressure, heart rate, salivary testosterone and cortisol levels were measured under resting and anxiety conditions in the spring and summer. Data were collected from 46 participants during the spring (n=25) and summer (n=21). Results Pain thresholds and testosterone levels were significantly lower under anxiety than at rest for all participants (n=46), while cortisol levels, pain ratings, and anxiety ratings were significantly higher under anxiety than at rest. In the spring (n=25), testosterone levels were significantly higher at rest than under anxiety, while there was no difference in cortisol levels between resting and anxiety conditions. In the summer (n=21), cortisol levels were significantly higher under anxiety than at rest, while there was no difference in testosterone levels between resting and anxiety conditions. There were no significant seasonal differences in pain and anxiety ratings and pain threshold. Conclusion These results indicate that seasonal differences in testosterone and cortisol levels under anxiety and at rest may affect pain responses. These results also suggest that acute clinical pain may be relieved by managing anxiety that is related to a decrease of testosterone in spring and a large increase of cortisol in summer.
Lee, Jong Hyuk; Choi, Eunhee; Chung, Myung-il; Seo, Sang Min; Lim, Hyun Kyo
Endocrines, the chief components of chemical centers which produce hormones in tune with intrinsic and extrinsic clues, create a chemical bridge between the organism and the environment. In fishes also hormones integrate and modulate many physiologic functions and its synthesis, release, biological actions and metabolic clearance are well regulated. Consequently, thyroid hormones (THs) and cortisol, the products of thyroid and
Valsa S. Peter; M. C. Subhash Peter
Background: Roots of cruciferous plant Lepidium peruvianum Chacon cultivated in high plateaus of Andes and known under its common name Maca, have been traditionally-used as an energizing vegetable with therapeutic properties for both men and women. Maca has been recognized by natives of Peru as herbal remedy helping to treat conditions affecting menopausal women. Objective: The effects of Pre-Gelatinized Organic Maca (Maca-GO) on quantitative physiological responses and alleviation of symptoms contributing to menopausal discomfort in perimenopausal women was examined. Methods: In this, four months, double blind, crossover, randomized pilot trial, monthly measurements of the following blood serum constituents were taken: Estrogen (E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Progesterone (PGS), Cortisol (CT), Adrenocorticotropic Hormone (ACTH), Thyroid Hormones (TSH, T3, T4), minerals (Ca, K, Fe) and lipid profile (Triglicerides, Total Cholesterol, LDL, HDL). In monthly interviews conducted by gynecologist, body weight and blood pressure were registered and Menopausal Index according to Kupperman’s was determined. Toxicity of Maca -GO determined on rats showed its safe use at the level of 7.5mg/kg body weight. A group of 20 women (aged 41-50 years), who fulfilled criteria of being in perimenopausal stage (E2 above 40pg/ml and FSH below 30IU/ml), were randomly allocated to two even groups, one receiving for two months Maca-GO and the other Placebo capsules followed by a crossover with treatment change for another two months period. All participants signed informed consent to participate. Two 500mg hard capsules with Maca-GO or Placebo were self-administered by participants twice daily with meals (total 2g/day). Results: Two months administration of Maca-GO significantly alleviated symptoms of discomfort observed in majority of women involved in the study (74%-87%) as assessed by Kupperman’s Menopausal index. This was associated with significant increase in E2 and FSH, Progesterone and ACTH levels, and reduction in blood pressure, body weight, Triglycerides and Cholesterol levels. There was a distinctive placebo effect observed at the beginning of the study. Conclusions: The results showed that in addition to reduction in body weight, blood pressure and increasing serum HDL and Iron, pre-gelatinized Maca-GO may be a valuable non-hormonal plant preparation for balancing levels of hormones (FSH, E2, PG and ACTH) and alleviating negative physiological and psychological symptoms (frequency of hot flushes, incidence in night sweating, interrupted sleep pattern, nervousness, depression and heart palpitations) experienced by women in perimenopausal stage. It appears that Maca-GO may act as a toner of hormonal processes, leading to alleviation of discomfort felt by perimenopausal women, hence, its potential use as non-hormonal alternative to HRT program.
Meissner, H. O.; Reich-Bilinska, H.; Mscisz, A.; Kedzia, B.
Insulin and cortisol play a key role in the regulation of energy homeostasis, appetite, and satiety. Little is known about the action and interaction of both hormones in brain structures controlling food intake and the processing of neurovisceral signals from the gastrointestinal tract. In this study, we assessed the impact of single and combined application of insulin and cortisol on resting regional cerebral blood flow (rCBF) in the insular cortex. After standardized periods of food restriction, 48 male volunteers were randomly assigned to receive either 40 IU intranasal insulin, 30 mg oral cortisol, both, or neither (placebo). Continuous arterial spin labeling (CASL) sequences were acquired before and after pharmacological treatment. We observed a bilateral, locally distinct rCBF increase after insulin administration in the insular cortex and the putamen. Insulin effects on rCBF were present regardless of whether participants had received cortisol or not. Our results indicate that insulin, but not cortisol, affects blood flow in human brain structures involved in the regulation of eating behavior. PMID:23907764
Schilling, Thomas M; Ferreira de Sá, Diana S; Westerhausen, René; Strelzyk, Florian; Larra, Mauro F; Hallschmid, Manfred; Savaskan, Egemen; Oitzl, Melly S; Busch, Hans-Peter; Naumann, Ewald; Schächinger, Hartmut
Developmental psychologists have long been concerned with the ways that early adversity influences children’s long-term outcomes. In the current study, activity of the HPA axis of medically at-risk (e.g., preterm) infants was measured as a result of maternal participation in a novel cognitively-based home visitation program (versus a Healthy Start home visitation program). Maternal participation in the cognitive intervention predicted lower basal cortisol levels among infants – with reduced levels of maternal avoidance/withdrawal serving as a mediator of this relation. Lower cortisol levels in infancy, in turn, predicted higher verbal short-term memory at age 3. Short-term memory represents a cognitive ability that has importance for children’s later educational outcomes. Findings provide experimental evidence concerning the pathway by which an early intervention may produce hormonal changes that can, in turn, influence children’s learning outcomes.
Bugental, Daphne Blunt; Schwartz, Alex; Lynch, Colleen
Apart from their role in cardiovascular homeostasis and immunomodulation, aldosterone and cortisol are also implicated in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM). Furthermore, glycoxidative modifications of lipoproteins are increasingly recognized as an etiological factor for increased cardiovascular morbidity and mortality in prediabetic individuals. The causative relationship between in vivo lipoprotein modifications and steroidogenesis in subjects with impaired glucose tolerance (IGT), however, is not well defined. Therefore, we aimed to investigate the impact of in vivo modified lipoproteins on aldosterone and cortisol release from human adrenocortical H295R cells. Following an oral glucose tolerance test, 20 individuals with normal glucose tolerance (NGT) and 20 IGT subjects were randomly selected from the ongoing PRAEDIAS prevention study in our department. Cells were incubated for 24 h with lipoproteins isolated from NGT and IGT individuals and aldosterone and cortisol release was measured in the supernatants. VLDL induced a greater stimulating effect on adrenocortical aldosterone and cortisol release compared to HDL and LDL. Moreover, IGT-VLDL evoked a significantly higher effect (p<0.05) on hormone release than NGT-VLDL. Incubation of cells with in vitro modified lipoproteins and specific pharmacological inhibitors suggests that VLDL presumably recruits ERK1/2 as one of the downstream effectors of Jak-2. In summary, in vivo modified VLDL are able to promote prediabetic hormonal dysregulation by modulating adrenocortical steroidogenesis via Jak-2-ERK dependent pathway. PMID:23047828
Saha, S; Schwarz, P E H; Bergmann, S; Bornstein, S R; Graessler, J; Kopprasch, S
Context Fetal stress is relevant to newborn outcomes. Corticosterone is rarely quantified in human clinical endocrinology and is found at much lower concentrations than cortisol. However, fetal corticosterone is a candidate hormone as a fetal stress signal. Objective Test the hypothesis that preferential fetal corticosterone synthesis occurs in response to fetal intra-partum stress. Design Cross-sectional comparison of paired serum corticosteroid concentrations in umbilical artery and vein from 300 women providing consent at admission to a General Hospital Labor and Delivery unit. Pre-term and multiple births were excluded, leaving 265 healthy deliveries. Main Outcome Measures Corticosterone and cortisol concentrations determined by LC-MS/MS for umbilical cord venous (V) and arterial (A) samples and used to calculate fetal synthesis (A?V) and proportional fetal synthesis ([A?V]/V). Chart-derived criteria stratified samples by type of delivery, maternal regional analgesia, augmentation of contractions, and clinical rationale for emergent Caesarian delivery. Results Cortisol concentrations were higher than corticosterone concentrations; however, the fetus preferentially secretes corticosterone (148% vs 49% proportional increase for cortisol) and differentially secretes corticosterone as fetal stress increases. Fetal corticosterone synthesis is elevated after passage through the birth canal relative to Caesarian deliveries. For vaginal deliveries, augmentation of contractions does not affect corticosteroid concentrations whereas maternal regional analgesia decreases venous (maternal) concentrations and increases fetal synthesis. Fetal corticosterone synthesis is also elevated after C-section indicated by cephalopelvic disproportion after labor, whereas cortisol is not. Conclusions The full-term fetus preferentially secretes corticosterone in response to fetal stress during delivery. Fetal corticosterone could serve as a biomarker of fetal stress.
Wynne-Edwards, Katherine E.; Edwards, Heather E.; Hancock, Trina M.
This study was performed to investigate stress effects on the synthesis of egg yolk precursor, vitellogenin (Vtg) in Arctic char (Salvelinus alpinus). In particular the effect of cortisol (F) was determined since this stress hormone has been suggested to interfere with vitellogenesis and is upregulated during sexual maturation in teleosts. Arctic char Vtg was purified and polyclonal antibodies were produced
Hakan Berg; Carina Modig; Per-Erik Olsson
While detectable levels of non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in various aquatic habitats, little is known about the mechanism of action of these pharmaceutical drugs on organisms. Recently we demonstrated that NSAIDs disrupt corticosteroidogenesis in rainbow trout (Oncorhynchus mykiss). As cortisol is a seawater adapting hormone, we hypothesized that exposure to NSAIDs will impair the hyposmoregulatory capacity of
Amélie Gravel; Jonathan M. Wilson; Dalila F. N. Pedro; Mathilakath M. Vijayan
The relationships among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarattes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. This data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism.
Seyler, L.E. Jr.; Fertig, J.; Pomerleau, O.; Hunt, D.; Parker, K.
To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses.
Bessey, P Q; Watters, J M; Aoki, T T; Wilmore, D W
Estradiol has potent favorable effects on brain function and behavior in animals while in human trials, the results are inconsistent. A number of potential mediating variables influencing response to estradiol have been proposed to account for this variability, 1 of which includes stress. We conducted a placebo-controlled study to examine joint and independent effects of estradiol and elevated levels of the stress hormone cortisol on cognition and biomarkers of aging and neurodegenerative disease. Thirty-nine healthy postmenopausal women (56-84 years) received 0.10 mg/dL of transdermal 17?-estradiol (E2) or placebo for 8 weeks. During the last 4 days of the trial, subjects also received 90 mg/day (30 mg 3×/day) of oral hydrocortisone (CORT) to induce stress-level elevations in cortisol, or a matched placebo. The 4 groups thus included placebo (placebo patch/placebo pill), CORT-alone (placebo patch/hydrocortisone), E2-alone (estradiol patch/placebo pill), and E2+CORT (estradiol patch/hydrocortisone). Eight weeks of E2 increased plasma estradiol by 167%, and 4 days of CORT increased plasma cortisol by 119%. Overall, E2 had favorable effects on verbal memory (p = 0.03), working memory (p = 0.02), and selective attention (p = 0.04), and the magnitude of these effects was attenuated for E2+CORT. E2-alone and E2+CORT had opposing effects on plasma levels of the amyloid-? (A?) biomarker (A?40/42 ratio, p < 0.05), with the more favorable response observed for E2-alone. CORT-induced increases in insulin-like growth factor-1 were blunted by E2 coadministration. Our findings indicate that cognitive and physiological responses to estradiol are adversely affected by elevated stress hormone levels of cortisol in healthy postmenopausal women. PMID:21855173
Baker, Laura D; Asthana, Sanjay; Cholerton, Brenna A; Wilkinson, Charles W; Plymate, Stephen R; Green, Pattie S; Merriam, George R; Fishel, Mark A; Watson, G Stennis; Cherrier, Monique M; Kletke, Monica L; Mehta, Pankaj D; Craft, Suzanne
Estradiol has potent favorable effects on brain function and behavior in animals while in human trials, the results are inconsistent. A number of potential mediating variables influencing response to estradiol have been proposed to account for this variability, one of which includes stress. We conducted a placebo-controlled study to examine joint and independent effects of estradiol and elevated levels of the stress hormone cortisol on cognition and biomarkers of aging and neurodegenerative disease. Thirty-nine healthy postmenopausal women (56-84 yrs) received 0.10 mg/d of transdermal 17?-estradiol (E2) or placebo for eight weeks. During the last four days of the trial, subjects also received 90 mg/d (30 mg TID) of oral hydrocortisone (CORT) to induce stress-level elevations in cortisol, or a matched placebo. The four groups thus included Placebo (placebo patch/placebo pill), CORT-alone (placebo patch/hydrocortisone), E2-alone (estradiol patch/placebo pill), and E2+CORT (estradiol patch/hydrocortisone). Eight weeks of E2 increased plasma estradiol by 167%, and four days of CORT increased plasma cortisol by 119%. Overall, E2 had favorable effects on verbal memory (p=0.03), working memory (p=0.02), and selective attention (p=0.04), and the magnitude of these effects was attenuated for E2+CORT. E2-alone and E2+CORT had opposing effects on plasma levels of the amyloid-? (A?) biomarker (A?40/42 ratio, p<0.05), with the more favorable response observed for E2-alone. CORT-induced increases in insulin-like growth factor-1 were blunted by E2 co-administration. Our findings indicate that cognitive and physiological responses to estradiol are adversely affected by elevated stress hormone levels of cortisol in healthy postmenopausal women.
Baker, Laura D; Asthana, Sanjay; Cholerton, Brenna A; Wilkinson, Charles W; Plymate, Stephen R; Green, Pattie S; Merriam, George R; Fishel, Mark A; Watson, G Stennis; Cherrier, Monique M; Kletke, Monica L; Mehta, Pankaj D; Craft, Suzanne
Trauma is associated with alterations in cortisol activity and reactivity that may vary in relationship to development, time, predisposition, personality, the nature of a traumatic event, and other circumstances. This article reviews existing research findings related to cortisol in laboratory, general stress, and traumatic conditions. We discuss variables that may influence cortisol activity and reactivity in an effort to discover
Kathleen Nader; Carl F. Weems
Cortisol is the principal corticosteriod in teleost fishes and its plasma concentrations rise dramatically during stress. The relationship between this cortisol increase and its metabolic consequences are subject to extensive debate. Much of this debate arises from the different responses of the many species used, the diversity of approaches to manipulate cortisol levels, and the sampling techniques and duration. Given
Thomas P. Mommsen; Mathilakath M. Vijayan; Thomas W. Moon
Pharmacological doses of melatonin—low (0.5 mg\\/kg body wt.) and high (1.0 mg\\/kg body wt.) doses were administered chronically for 45 days to Wistar rats, and 24 h rhythms of adrenocorticotrophic hormone, cortisol, growth hormone, prolactin and melatonin were studied under semi-natural conditions. Exogenous melatonin administration caused delays in the acrophases of growth hormone and melatonin rhythm itself, whereas advances in the acrophases of
S. Mirunalini; P. Subramanian
Adrenal adenomas producing both aldosterone and cortisol (A\\/CPAs) have been described in only a few cases. Correct subtype classification is necessary for making therapeutic decisions in primary aldosteronism (PA). Therefore, we studied in detail the clinical, hormonal and histological features of this entity in two patients with A\\/CPAs. We describe two patients with A\\/CPA and present their endocrine evaluations at
Holger S Willenberg; Martin Späth; Christiane Maser-Gluth; Rainer Engers; Martin Anlauf; Gabriele Dekomien; Matthias Schott; Sven Schinner; Kenko Cupisti; Werner A Scherbaum
Northern elephant seal (Mirounga angustirostris) pups rely on the oxidation of fat stores as their primary source of energy during their 8- to 12-wk postweaning fast; however, potential endocrine mechanisms involved with this increased fat metabolism have yet to be examined. Therefore, 15 pups were serially blood sampled in the field during the first 7 wk of their postweaning fast to examine the changes in plasma concentrations of cortisol and thyroid hormones (TH), which are involved in fat metabolism in other mammals. Cortisol increased, indicating that it contributed to an increase in lipolysis. Increased total triiodothyronine (tT(3)) and thyroxine (tT(4)) may not reflect increased thyroid gland activity, but rather alterations in hormone metabolism. tT(3)-to-tT(4) ratio decreased, suggesting a decrease in thyroxine (T(4)) deiodination, whereas the negative correlation between total proteins and free T(4) suggests that the increase in free hormone is attributed to a decrease in binding globulins. Changes in TH are most similar to those observed during hibernation than starvation in mammals, suggesting that the metabolic adaptations to natural fasting are more similar to hibernation despite the fact these animals remain active throughout the fasting period.
Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.
The purpose of this study was to assess changes in the steroid hormone levels of elite athletes during an international powerlifting competition. Baseline cortisol, DHEA and testosterone were determined in saliva samples in 19 (8 men, 11 women) junior and sub-junior athletes on the day before competition, and then on the competition day during the official weighing and in the hour after competition. Performance was determined by total output and the Wilks formula. No change in saliva steroid concentrations was observed between samples collected on the day before competition and the weighing samples. There was no gender effect on cortisol concentrations but saliva testosterone levels were always significantly higher in men than in women (p<0.01), as was end-competition DHEA (p<0.05). Cortisol and DHEA were significantly increased in male and female athletes after the competition (respectively, p<0.01 and p<0.05), whereas end-competition testosterone concentrations were only significantly increased in men (p<0.01). Significant relationships were demonstrated between performance and end-competition cortisol levels in women and end-competition testosterone levels in men. These data indicate that workouts during an international powerlifting competition produce a significant increase in adrenal steroid hormones in both genders, with an increase in male gonadal steroid hormone. Further studies are necessary to examine the changes in oestradiol and progesterone in women and their potential impact on performance during international powerlifting competition. PMID:22917632
Le Panse, Bénédicte; Labsy, Zakaria; Baillot, Aurélie; Vibarel-Rebot, Nancy; Parage, Gaston; Albrings, Detlev; Lasne, Françoise; Collomp, Katia
Background Cortisol is presumed to be a risk factor for stress- and age-related disorders, such as depressive disorder and Alzheimer’s disease (AD). The aim of this study was to investigate the association of plasma cortisol concentration with AD in presence or absence of comorbid depressive symptoms. Material/Methods Plasma cortisol concentration was measured in 80 AD patients (35 of them with depressive symptoms), 27 elderly depressive patients without AD, and 37 elderly controls. Results Compared to controls, a significant increase of mean plasma cortisol was found in AD patients but not in depressive patients. Plasma cortisol was positively correlated with cognitive impairment in AD patients. We confirmed a U-shaped association between plasma cortisol and major depression and a linear association between plasma cortisol and AD without depressive symptoms. Significantly increased relative risk of disease in people with high plasma cortisol was found for AD with depressive symptoms and for AD with mild dementia. Conclusions Plasma cortisol reflects the degree of cognitive impairment in AD rather than the severity of comorbid depression. We confirmed that both hypercortisolemia and hypocortisolemia are associated with depressive disorder. Significant association between high plasma cortisol and AD was found, supporting the use of high plasma cortisol as a component of a panel of biochemical markers for AD with depressive symptoms as well as AD in the early stage of dementia development.
Zverova, Martina; Fisar, Zdenek; Jirak, Roman; Kitzlerova, Eva; Hroudova, Jana; Raboch, Jiri
This paper describes a possible framework of hormones and their binding proteins (BPs) that might be responsible for the increased incidence of depression in women, including postnatal depression. It is based on three reported facts: Increased cortisol exposure reduces growth hormone (GH) secretion. Cortisol and GH show opposite effects on mood. Liver secretion of various hormone binding proteins is increased under estrogen exposure. If we accept that pure cortisol exposure leads to depressive mood, while simultaneous brain exposure to cortisol and an anabolic (growth hormone or somatomammotropin) is less mood affecting, the occurrence of depression an be more likely in persons: with altered sleep patterns and thus reduced GH secretion, in individuals with increased chronic cortisol exposure (any individual under repeated or sustained stress, older individuals with stressful memories, etc.). The proposed mechanism can be enhanced in women of reproductive age through increased transcortin and GH BP pools due to estrogen action on liver. A particularly vulnerable phase seems to be the early postnatal period, when sudden discontinuation of somatomammotropin anabolic actions might lead to postnatal depression that takes weeks or months to resolve, until the GH/cortisol circadian rhythm normalization. PMID:18996648
Dodig-Curkovic, Katarina; Kurbel, Sven; Matic, Vesna Cacinovic
Branched-chain amino acids (BCAA) are actively taken up and catabolized by the mammary gland during lactation for syntheses of glutamate, glutamine and aspartate. Available evidence shows that the onset of lactation is associated with increases in circulating levels of cortisol, prolactin and glucagon, but decreases in insulin and growth hormone. This study determined the effects of physiological concentrations of these hormones on the catabolism of leucine (a representative BCAA) in bovine mammary epithelial cells. Cells were incubated at 37 °C for 2 h in Krebs buffer containing 3 mM D-glucose, 0.5 mM L-leucine, L-[1-14C]leucine or L-[U-14C]leucine, and 0-50 ?U/mL insulin, 0-20 ng/mL growth hormone 0-200 ng/mL prolactin, 0-150 nM cortisol or 0-300 pg/mL glucagon. Increasing extracellular concentrations of insulin did not affect leucine transamination or oxidative decarboxylation, but decreased the rate of oxidation of leucine carbons 2-6. Elevated levels of growth hormone dose dependently inhibited leucine catabolism, ?-ketoisocaproate (KIC) production and the syntheses of glutamate plus glutamine. In contrast, cortisol and glucagon increased leucine transamination, leucine oxidative decarboxylation, KIC production, the oxidation of leucine 2-6 carbons and the syntheses of glutamate plus glutamine. Prolactin did not affect leucine catabolism in the cells. The changes in leucine degradation were consistent with alterations in abundances of BCAA transaminase and phosphorylated levels of branched-chain ?-ketoacid dehydrogenase. Reductions in insulin and growth hormone but increases in cortisol and glucagon with lactation act in concert to stimulate BCAA catabolism for glutamate and glutamine syntheses. These coordinated changes in hormones may facilitate milk production in lactating mammals. PMID:22707151
Lei, Jian; Feng, Dingyuan; Zhang, Yongliang; Dahanayaka, Sudath; Li, Xilong; Yao, Kang; Wang, Junjun; Wu, Zhenlong; Dai, Zhaolai; Wu, Guoyao
Aqueous humor (AqH) has been shown to have significant immunosuppressive effects on APCs in animal models. We wanted to establish whether, in humans, AqH can regulate dendritic cell (DC) function and to identify the dominant mechanism involved. Human AqH inhibited the capacity of human peripheral blood monocyte-derived DC to induce naive CD4(+) T cell proliferation and cytokine production in vitro, associated with a reduction in DC expression of the costimulatory molecule CD86. This was seen both for DC cultured under noninflammatory conditions (immature DC) and for DC stimulated by proinflammatory cytokines (mature DC). DC expression of MHC classes I/II and CD83 was reduced (mature DC only). Myeloid DC from peripheral blood were similarly sensitive to the effects of human AqH, but only under inflammatory conditions. The addition of ?-melanocyte stimulating hormone and vasoactive intestinal peptide did not cause significant inhibition at physiological levels. However, the addition of exogenous cortisol at physiological levels recapitulated the AqH-induced reduction in CD86 and inhibition of DC-induced T cell proliferation, and blockade of cortisol in AqH partially reversed its suppressive effects. TGF-?2 had an additional effect with cortisol, and although simultaneous blockade of cortisol and TGF-?2 in AqH reduced its effectiveness, there was still a cortisol- and TGF-?-independent component. In humans, AqH regulates DC maturation and function by the combined actions of cortisol and TGF-?2, a pathway that is likely to contribute to the maintenance of immune privilege in the eye. PMID:21106846
Denniston, Alastair K; Kottoor, Sherine H; Khan, Imran; Oswal, Kadambari; Williams, Geraint P; Abbott, Joseph; Wallace, Graham R; Salmon, Mike; Rauz, Saaeha; Murray, Philip I; Curnow, S John
Although excessive glucocorticoids are a well-recognized cause of osteoporosis, little is known about the role of endogenous glucocorticoids in determining skeletal mass. We have performed a detailed study of the hypothalamic-pituitary-adrenal (HPA) axis to explore the relationships between cortisol secretion and adult bone mass in 151 healthy men and 96 healthy women aged 61 to 73 years. At baseline and 4-year follow-up, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur; a lifestyle questionnaire was completed; and height, weight, and waist and hip circumferences were measured. At follow-up subjects underwent a very low-dose (0.25 mg) dexamethasone suppression test, a low-dose (1 microg) short synacthen test, and a 24-hour urine collection for measurement of cortisol and its metabolites. In men, elevated peak plasma cortisol was associated with accelerated loss of mineral density in the lumbar spine (r = 0.16, P = 0.05). This relationship remained significant after adjustment for testosterone, estradiol, 25-hydroxyvitamin D, and parathyroid hormone levels (r = 0.22, P = 0.01) and after additional adjustment for age, (BM), activity, cigarette and alcohol consumption, and Kellgren/Lawrence score (r = 0.19, P = 0.03). In contrast in women, elevated peak plasma cortisol was associated with lower baseline BMD at the femoral neck (r = -0.23, P = 0.03) and greater femoral neck loss rate (r = 0.24, P = 0.02). There was no association between plasma cortisol concentrations after dexamethasone or urinary total cortisol metabolite excretion and bone density or bone loss rate at any site. These data provide evidence that circulating endogenous glucocorticoids influence the rate of involutional bone loss in healthy individuals. PMID:16151676
Reynolds, R M; Dennison, E M; Walker, B R; Syddall, H E; Wood, P J; Andrew, R; Phillips, D Iw; Cooper, C
The hypothalamic-pituitary-adrenal (HPA)-axis is a central component of the body's neuroendocrine response to stress. Its major end-product cortisol has profound effects on mood and behavior. Although it has often been suggested, it remains unknown whether differences in HPA-axis physiology are part of an individual's vulnerability to psychopathology, and constitute a causal factor in its development. In order to study the contribution of HPA-axis physiology to the development of psychopathology, we measured HPA-axis physiology in a community-cohort of 1768 10-12 year-old children. The aims of the here presented study were twofold: (1) to obtain data on HPA-axis function in a large cohort of pre- and early-adolescent children, both in terms of total hormonal output and in terms of the dynamics of cortisol secretion (by means of the cortisol awakening response); and (2) to study potential confounders of the cortisol-psychopathology relationship in this age group, such as season of sampling, age, gender, pubertal development, perinatal variables and BMI. We found a wide interindividual variability in HPA-axis function. An increase in cortisol in the first 30 min after awakening was present in 70.7% of children, but the increase appears lower in children than in adults. In addition, this study suggests that season of sampling and gender may act as potential confounders in the cortisol-psychopathology relationship. We will follow these children longitudinally for the development of psychopathology in the period from childhood into adulthood. This period covers adolescence, which is a critical time for the appearance and development of psychiatric disorders. PMID:15721059
Rosmalen, J G M; Oldehinkel, A J; Ormel, J; de Winter, A F; Buitelaar, J K; Verhulst, F C
Levels of cortisol, a hormone produced by the adrenal gland, follow a daily, 24-hour rhythm with concentrations reaching a minimum in the evening and a peak near rising time. In addition, cortisol levels exhibit a sharp peak in concentration within the first hour after waking; this is known as the cortisol awakening response (CAR). The present study is a secondary analysis of a larger study investigating the impact of short-wavelength (?max ? 470?nm) light on CAR in adolescents who were sleep restricted. The study ran over the course of three overnight sessions, at least one week apart. The experimental sessions differed in terms of the light exposure scenarios experienced during the evening prior to sleeping in the laboratory and during the morning after waking from a 4.5-hour sleep opportunity. Eighteen adolescents aged 12–17 years were exposed to dim light or to 40 lux (0.401?W/m2) of 470-nm peaking light for 80 minutes after awakening. Saliva samples were collected every 20 minutes to assess CAR. Exposure to short-wavelength light in the morning significantly enhanced CAR compared to dim light. Morning exposure to short-wavelength light may be a simple, yet practical way to better prepare adolescents for an active day.
Figueiro, Mariana G.; Rea, Mark S.
Endocrine time series often lack normality and homoscedasticity most likely due to the non-linear dynamics of their natural determinants and the immanent characteristics of the biochemical analysis tools, respectively. As a consequence, data transformation (e.g., log-transformation) is frequently applied to enable general linear model-based analyses. However, to date, data transformation techniques substantially vary across studies and the question of which is the optimum power transformation remains to be addressed. The present report aims to provide a common solution for the analysis of endocrine time series by systematically comparing different power transformations with regard to their impact on data normality and homoscedasticity. For this, a variety of power transformations of the Box-Cox family were applied to salivary cortisol data of 309 healthy participants sampled in temporal proximity to a psychosocial stressor (the Trier Social Stress Test). Whereas our analyses show that un- as well as log-transformed data are inferior in terms of meeting normality and homoscedasticity, they also provide optimum transformations for both, cross-sectional cortisol samples reflecting the distributional concentration equilibrium and longitudinal cortisol time series comprising systematically altered hormone distributions that result from simultaneously elicited pulsatile change and continuous elimination processes. Considering these dynamics of endocrine oscillations, data transformation prior to testing GLMs seems mandatory to minimize biased results. PMID:23063878
Miller, Robert; Plessow, Franziska
Glucocorticoids serve important regulatory functions for many physiological processes and are critical mediators of the stress response. The stress response is a set of bodily processes aimed at counteracting a state of threatened homeostasis. Proper stress response is critical for the survival of an animal, however prolonged or abnormal stress response can be detrimental and is implicated in a number of human diseases such as depression and metabolic diseases. To dissect the underlying mechanism of this complex and important response, the zebrafish, Danio rerio offer important advantages such as ease of genetic manipulations and high-throughput behavioral analyses. However, there is a paucity of suitable methods to measure stress level in larval zebrafish. Therefore, an efficient low-cost method to monitor stress hormone levels will greatly facilitate stress research in zebrafish larvae. In this study, we optimized sample collection as well as cortisol extraction methods and developed a home-made ELISA protocol for measuring whole-body cortisol level in zebrafish larvae. Further, using our customized protocols, we characterized the response of larval zebrafish to a variety of stressors. This assay, developed for efficient cortisol quantification, will be useful for systematic and large-scale stress analyses in larval zebrafish. PMID:24223943
Yeh, Chen-Min; Glöck, Mario; Ryu, Soojin
While much attention has been devoted to examining the beneficial effects of Mindfulness-Based Stress Reduction programs on patients' ability to cope with various chronic medical conditions, most studies have relied on self-report measures of improvement. Given that these measures may not accurately reflect physiological conditions, there is a need for an objective marker of improvement in research evaluating the beneficial effects of stress management programs. Cortisol is the major stress hormone in the human organism and as such is a promising candidate measure in the study of the effects of Mindfulness-Based Stress Reduction programs. In conjunction with other biological measures, the use of cortisol levels as a physiological marker of stress may be useful to validate self-reported benefits attributed to this program. In the current manuscript, we review the available literature on the role of cortisol as a physiological marker for improvement with regards to mindfulness practice, and make recommendations for future study designs. PMID:20129404
Matousek, Rose H; Dobkin, Patricia L; Pruessner, Jens
Summary Seventeen male physical education students performed three types of treadmill exercise: (1) progressive exercise to exhaustion, (2) prolonged exercise of 50 min duration at the anaerobic threshold of 4 mmol·1–1 blood lactate (AE), (3) a single bout of short-term high-intensity exercise at 156% of maximal exercise capacity in the progressive test, leading to exhaustion within 1.5 min (ANE).Immediately before and
W. Kindermann; A. Schnabel; W. M. Schmitt; G. Biro; J. Cassens; F. Weber
Diurnal cortisol is a marker of HPA-axis activity that may be one of the biological mechanisms linking stressors to age-related health declines. The current study identified day-centered profiles of diurnal cortisol among 1101 adults living in the United States. Participants took part in up to four consecutive days of salivary cortisol collection, assessed at waking, 30min post-waking, before lunch, and before bedtime. Growth mixture modeling with latent time basis was used to estimate common within-day trajectories of diurnal cortisol among 2894 cortisol days. The 3-class solution provided the best model fit, showing that the majority of study days (73%) were characterized by a Normative cortisol pattern, with a robust cortisol awakening response (CAR), a steep negative diurnal slope, coupled with low awakening and bedtime levels. Relative to this profile, diurnal cortisol on the remainder of days appeared either elevated throughout the day (20% of days) or flattened (7% of days). Relative to the normative trajectory, the elevated trajectory was distinguished by a higher morning cortisol level, whereas the flattened trajectory was characterized by a high bedtime level, with weaker CAR and diurnal slope parameters. Relative to the normative profile, elevated profile membership was associated with older age and cigarette smoking. Greater likelihood of the flattened cortisol pattern was observed among participants who were older, male, smoked cigarettes, used medications that are known to affect cortisol output, and reported poorer health. The current study demonstrates the value of a day-centered growth mixture modeling approach to the study of diurnal cortisol, showing that deviations from the classic robust rhythm of diurnal cortisol are associated with older age, male sex, use of medications previously shown to affect cortisol levels, poorer health behaviors, and poorer self-reported health. PMID:23770247
Dmitrieva, Natalia O; Almeida, David M; Dmitrieva, Julia; Loken, Eric; Pieper, Carl F
It has long been held that cortisol, acting through a single receptor, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. The recent finding that fish express a gene with high sequence similarity to the mammalian mineralocorticoid receptor (MR) suggests the possibility that a hormone other than cortisol carries out some mineralocorticoid functions in fish. To test for this possibility, we examined the effect of in vivo cortisol, 11-deoxycorticosterone (DOC) and aldosterone on salinity tolerance, gill Na+,K+-ATPase (NKA) activity and mRNA levels of NKA ?1a and ?1b in Atlantic salmon. Cortisol treatment for 6–14 days resulted in increased, physiological levels of cortisol, increased gill NKA activity and improved salinity tolerance (lower plasma chloride after a 24 h seawater challenge), whereas DOC and aldosterone had no effect on either NKA activity or salinity tolerance. NKA ?1a and ?1b mRNA levels, which increase in response to fresh water and seawater acclimation, respectively, were both upregulated by cortisol, whereas DOC and aldosterone were without effect. Cortisol, DOC and aldosterone had no effect on gill glucocorticoid receptor GR1, GR2 and MR mRNA levels, although there was some indication of possible upregulation of GR1 by cortisol (p = 0.07). The putative GR blocker RU486 inhibited cortisol-induced increases in salinity tolerance, NKA activity and NKA ?1a and ?1b transcription, whereas the putative MR blocker spironolactone had no effect. The results provide support that cortisol, and not DOC or aldosterone, is involved in regulating the mineralocorticoid functions of ion uptake and salt secretion in teleost fish.
McCormick, S. D.; Regish, A.; O'Dea, M. F.; Shrimpton, J. M.
Are we missing a mineralocorticoid in teleost fish? Effects of cortisol, deoxycorticosterone and aldosterone on osmoregulation, gill Na+,K+ -ATPase activity and isoform mRNA levels in Atlantic salmon.
It has long been held that cortisol, acting through a single receptor, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. The recent finding that fish express a gene with high sequence similarity to the mammalian mineralocorticoid receptor (MR) suggests the possibility that a hormone other than cortisol carries out some mineralocorticoid functions in fish. To test for this possibility, we examined the effect of in vivo cortisol, 11-deoxycorticosterone (DOC) and aldosterone on salinity tolerance, gill Na(+),K(+)-ATPase (NKA) activity and mRNA levels of NKA alpha 1a and alpha 1b in Atlantic salmon. Cortisol treatment for 6-14 days resulted in increased, physiological levels of cortisol, increased gill NKA activity and improved salinity tolerance (lower plasma chloride after a 24h seawater challenge), whereas DOC and aldosterone had no effect on either NKA activity or salinity tolerance. NKA alpha 1a and alpha 1b mRNA levels, which increase in response to fresh water and seawater acclimation, respectively, were both upregulated by cortisol, whereas DOC and aldosterone were without effect. Cortisol, DOC and aldosterone had no effect on gill glucocorticoid receptor GR1, GR2 and MR mRNA levels, although there was some indication of possible upregulation of GR1 by cortisol (p=0.07). The putative GR blocker RU486 inhibited cortisol-induced increases in salinity tolerance, NKA activity and NKA alpha 1a and alpha 1b transcription, whereas the putative MR blocker spironolactone had no effect. The results provide support that cortisol, and not DOC or aldosterone, is involved in regulating the mineralocorticoid functions of ion uptake and salt secretion in teleost fish. PMID:18462736
McCormick, Stephen D; Regish, Amy; O'Dea, Michael F; Shrimpton, J Mark
Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (N = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. While repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.
Bauer, Charles R.; Lambert, Brittany L.; Bann, Carla M.; Lester, Barry M.; Shankaran, Seetha; Bada, Henrietta S.; Whitaker, Toni M.; LaGasse, Linda L.; Hammond, Jane; Higgins, Rosemary D.
Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (n = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. Although repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE. PMID:21546861
Bauer, Charles R; Lambert, Brittany L; Bann, Carla M; Lester, Barry M; Shankaran, Seetha; Bada, Henrietta S; Whitaker, Toni M; Lagasse, Linda L; Hammond, Jane; Higgins, Rosemary D
To fall in love is the first step in pair formation in humans and is a complex process which only recently has become the object of neuroscientific investigation. The little information available in this field prompted us to measure the levels of some pituitary, adrenal and gonadal hormones in a group of 24 subjects of both sexes who had recently (within the previous six months) fallen in love, and to compare them with those of 24 subjects who were single or were part of a long-lasting relationship. The following hormones were evaluated by means of standard techniques: FSH, LH, estradiol, progesterone, dehydroepiandrosterone sulphate (DHEAS), cortisol, testosterone and androstenedione. The results showed that estradiol, progesterone, DHEAS and androstenedione levels did not differ between the groups and were within the normal ranges. Cortisol levels were significantly higher amongst those subjects who had recently fallen in love, as compared with those who had not. FSH and testosterone levels were lower in men in love, while women of the same group presented higher testosterone levels. All hormonal differences were eliminated when the subjects were re-tested from 12 to 24 months later. The increased cortisol and low FSH levels are suggestive of the "stressful" and arousing conditions associated with the initiation of a social contact. The changes of testosterone concentrations, which varied in opposite directions in the two sexes, may reflect changes in behavioural and/or temperamental traits which have yet to be clarified. In conclusion, the findings of the present study would indicate that to fall in love provokes transient hormonal changes some of which seem to be specific to each sex. PMID:15177709
Marazziti, Donatella; Canale, Domenico
Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000nM) for 4h either in the presence or absence of ACTH (0.5IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of cortisol production in trout. PMID:21396343
Sandhu, Navdeep; Vijayan, Mathilakath M
Methods: Twelve premenopausal female patients with RA (39.8 (1.8) years) and nine healthy control women matched for age and body mass index (42 (3.3) years) were enrolled in the study. None of the patients had previously been receiving treatment with glucocorticoids. After dexamethasone suppression (2 mg by mouth) the evening before the study, 20 mg of hydrocortisone was given. Blood and saliva samples were drawn six hours after injection of hydrocortisone. Plasma and salivary cortisol were measured. Results: Dexamethasone administration suppressed plasma cortisol concentrations to an almost undetectable level in all subjects, except one with RA. In this subject, a raised concentration of plasma cortisol was verified by repeated analysis despite the fact that cortisol concentration in the saliva sample measured simultaneously was not raised. No significant difference in the disappearance curve of cortisol in plasma or in salivary cortisol levels was found between the patients with RA and the healthy controls. Conclusions: The profile of disappearance of total cortisol from plasma, and salivary cortisol levels during the elimination phase after its intravenous administration, are unchanged in premenopausal women with RA. Alterations in cortisol clearance are not likely to have a role in cortisol availability in patients with RA.
Rovensky, J; Imrich, R; Koska, J; Kovalancik, M; Killinger, Z; Payer, J; Vigas, M; Jezova, D
Background Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity. Aims To investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort. Method Young people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years. Results We found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14) before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression. Conclusions Our findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.
Carnegie, Rebecca; Araya, Ricardo; Ben-Shlomo, Yoav; Glover, Vivette; O'Connor, Thomas G.; O'Donnell, Kieran J.; Pearson, Rebecca; Lewis, Glyn
Objective: Basal cortisol and cortisol stress responsivity are valuable biological characteristics of children with disruptive behavior disorder (DBD). In this study, the predictive value of cortisol to outcome of intervention was investigated. Method: Basal cortisol levels and cortisol levels under stress were studied in 22 children with DBD…
van de Wiel, Nicolle M.H.; van Goozen, Stephanie H.M.; Matthys, Walter; Snoek, Heddeke; van Engeland, Herman
Summary Background Cortisol, a stress-related hormone, has been measured in many psychoimmunological studies via collection of saliva; however, patterns of participant adherence to protocol procedures are rarely described in the literature. Objectives In this paper we examine adherence to a cortisol morning rise collection protocol and explore its associations with demographic predictors and fatigue. Method Participants included 262 breast cancer survivors enrolled in a National Institute of Nursing Research funded longitudinal intervention study (5R01NR010190, M. Mishel, P.I.). Self-reported times of salivary cortisol collection were recorded for each of 12 saliva samples. Adherence was assessed with respect to various demographic factors and fatigue. Participants were categorized as having high, moderate, or low adherence to the saliva collection protocol. Results Overall, 117 (45%) participants had high adherence to the protocol, 117 (45%) participants had moderate adherence, and 28 (~11%) participants had low adherence. Tests for proportionality for the polytomous logistic regression indicated that demographic predictors in our model had a similar association with each level of participant adherence. Women who did not adhere to the saliva collection were more likely to be African American (OR .50, CI .29 – .88) and to report a high impact of fatigue on their behaviors (OR .88, CI .79 – .98). Though other predictors in the model were not statistically significant (working full time and living with at least one child under 18 years of age), the overall model was significant (?2(4) = 17.35, p<.01). Discussion To our knowledge, this is the first study to examine profiles of participant adherence to a cortisol sampling protocol over multiple timepoints. By conceptualizing adherence as a polytomous outcome, future studies may give us insights into adherence trends in other populations with the aim of promoting adherence and designing more informed saliva collection protocols.
Hall, Daniel; Blyler, Diane; Allen, Deborah; Mishel, Merle H; Crandell, Jamie; Germino, Barbara B; Porter, Laura S
The stress hormone cortisol (CORT) is slowly incorporated into the growing hair shaft of humans, nonhuman primates, and other mammals. We developed and validated a method for CORT extraction and analysis from rhesus monkey hair and subsequently adapted this method for use with human scalp hair. In contrast to CORT "point samples" obtained from plasma or saliva, hair CORT provides an integrated measure of hypothalamic-pituitary-adrenocortical (HPA) system activity, and thus physiological stress, during the period of hormone incorporation. Because human scalp hair grows at an average rate of 1 cm/month, CORT levels obtained from hair segments several cm in length can potentially serve as a biomarker of stress experienced over a number of months. In our method, each hair sample is first washed twice in isopropanol to remove any CORT from the outside of the hair shaft that has been deposited from sweat or sebum. After drying, the sample is ground to a fine powder to break up the hair's protein matrix and increase the surface area for extraction. CORT from the interior of the hair shaft is extracted into methanol, the methanol is evaporated, and the extract is reconstituted in assay buffer. Extracted CORT, along with standards and quality controls, is then analyzed by means of a sensitive and specific commercially available enzyme immunoassay (EIA) kit. Readout from the EIA is converted to pg CORT per mg powdered hair weight. This method has been used in our laboratory to analyze hair CORT in humans, several species of macaque monkeys, marmosets, dogs, and polar bears. Many studies both from our lab and from other research groups have demonstrated the broad applicability of hair CORT for assessing chronic stress exposure in natural as well as laboratory settings. PMID:24513702
Meyer, Jerrold; Novak, Melinda; Hamel, Amanda; Rosenberg, Kendra
Changes in oxytocin and cortisol levels were tested in healthy volunteers during hypnotic interactions in standardized laboratory sessions. Pre- to posthypnosis changes of oxytocin and cortisol were related to the hypnotic susceptibility of subjects and the relational experiences reposted by subjects and hypnotists on several paper-and-pencil tests. Results show that the changes in oxytocin are not related to hypnotic susceptibility but to relational experiences. After the hypnotic interaction, the subject's oxytocin level increased if perceived harmony with the hypnotist was high, whereas it increased in the hypnotist if the subject had memories of less warm emotional relationships with his or her parents. The results are interpreted within the social-psychobiological model of hypnosis. PMID:24256482
Varga, Katalin; Kekecs, Zoltán
The measurement of cortisol in saliva provides the basic scientist as well as the clinician with a reliable tool for investigations of hypothalamus-pituitary-adrenal axis activity. Since saliva samples can be obtained stress-free and independent from medically trained personnel this method may be well suited for use in psychobiological studies. This overview intends to give a comprehensive introduction to the method
Clemens Kirschbaum; Dirk H. Hellhammer
Emerging research suggests that rumination increases risk for negative health outcomes. In the first experiment to investigate\\u000a cortisol responses during angry rumination, participants were provoked and induced to engage in self-focused rumination, provocation-focused\\u000a rumination, or distraction. Consistent with social threat theory, self-focused rumination maintained high levels of cortisol\\u000a following provocation, whereas provocation-focused rumination and distraction facilitated decreases in cortisol. However,
Thomas F. Denson; Emma C. Fabiansson; J. David Creswell; William C. Pedersen
A rapid and semi-quantitative immunochromatographic strip (ICS) test for cortisol analysis in serum was developed. The test strip was based on a competitive assay format. Colloidal gold nanoparticles were synthesized and coupled with cortisol-3-carboxymethyloxime–adipic acid dihydrazide–bovine serum albumin (F-3-CMO–ADH–BSA) antigen to directly compete with cortisol in human serum samples. F-3-CMO–ADH–BSA–gold label and uncoupled colloidal gold nanoparticles were appropriately characterized using
Seema Nara; Vinay Tripathi; Harpal Singh; Tulsidas G. Shrivastav
The awakening cortisol response (ACR) is a discrete and distinctive part of the cortisol circadian cycle. In healthy adults salivary free cortisol concentrations increase by between 50 and 160% in the first 30 min immediately post-awakening (approximate average increase of 9 nmol\\/l, range 4 - 15 nmol\\/l, estimated to be equivalent to about three secretory episodes). However there are no
A. Clow; L. Thorn; P. Evans; F. Hucklebridge
It is hypothesized that hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes function together to maintain adaptive functioning during stressful situations differently in adolescence than the characteristic inverse relations found in adulthood. We examined within-person correlated changes (coupling) in cortisol, DHEA and testosterone in response to parent-adolescent conflict discussion, social performance, and venipuncture paradigms. Data are derived from two samples of boys and girls from the Northeastern US (213 adolescents aged 11-16, M=13.7, SD=1.5 years; 108 adolescents aged 9-14, M=11.99, SD=1.55) using different biological sampling vehicles (saliva and blood). Results consistently show that across samples, vehicles, and contexts, cortisol and DHEA and cortisol and testosterone are positively coupled in response to environmental stimuli. Findings underscore the importance of considering the effects of multiple hormones together in order to further our understanding of the biological underpinnings of behavior, especially during adolescence, as adolescence is a developmental transition period that may be qualitatively different from adulthood in terms of hormone functioning. PMID:24495606
Marceau, Kristine; Shirtcliff, Elizabeth A; Hastings, Paul D; Klimes-Dougan, Bonnie; Zahn-Waxler, Carolyn; Dorn, Lorah D; Susman, Elizabeth J
The present study was carried out to assess the endocrine status and liver function in adult cows reared in polluted environment around different industrial units in India.The effect on endocrine system was examined by determination of plasma level of thyroid hormones, thyroxin (T4) (n=269) and triidothyronin (T3) (n=269), stress hormone cortisol (n=266), and reproductive hormones such as estradiol (n=84) and
D. Swarup; Ram Naresh; V. P. Varshney; M. Balagangatharathilagar; P. Kumar; D. Nandi; R. C. Patra
Heat shock protein 70 (HSP70) expression was assessed in hepatic tissue of a marine teleost Sparus sarba after exogenous hormone administration. Using a PCR-amplified, homologous HSP70 cDNA clone, as a probe in Northern analysis, we detected a 2.3 kb transcript which was elevated after exposure to a temperature 7 degrees C above the ambient. For our studies on hormonal effects on HSP70 expression, groups of fish were administered recombinant bream GH (rbGH), ovine prolactin (oPRL) or cortisol daily over a 7-day period. Quantification of hepatic HSP70 transcript revealed that the administration of GH and PRL significantly reduced HSP70 mRNA abundance by 42% and 54% from saline-injected fish respectively. Also hepatic HSP70 levels were reduced by 76% and 64% as determined by immunoblotting after rbGH and oPRL treatment respectively. The administration of exogenous cortisol did not alter hepatic HSP70 mRNA or protein levels in S. sarba. The results obtained in this study are the first evidence for hormonal modulation of heat shock protein expression in fish. The significance of these results is discussed within the context of current knowledge on the roles of these hormones in teleostean stress response. PMID:10333544
Deane, E E; Kelly, S P; Lo, C K; Woo, N Y
Background The salmon louse is an ectoparasitic copepod that causes major economic losses in the aquaculture industry of Atlantic salmon. This host displays a high level of susceptibility to lice which can be accounted for by several factors including stress. In addition, the parasite itself acts as a potent stressor of the host, and outcomes of infection can depend on biotic and abiotic factors that stimulate production of cortisol. Consequently, examination of responses to infection with this parasite, in addition to stress hormone regulation in Atlantic salmon, is vital for better understanding of the host pathogen interaction. Results Atlantic salmon post smolts were organised into four experimental groups: lice + cortisol, lice + placebo, no lice + cortisol, no lice + placebo. Infection levels were equal in both treatments upon termination of the experiment. Gene expression changes in skin were assessed with 21 k oligonucleotide microarray and qPCR at the chalimus stage 18 days post infection at 9°C. The transcriptomic effects of hormone treatment were significantly greater than lice-infection induced changes. Cortisol stimulated expression of genes involved in metabolism of steroids and amino acids, chaperones, responses to oxidative stress and eicosanoid metabolism and suppressed genes related to antigen presentation, B and T cells, antiviral and inflammatory responses. Cortisol and lice equally down-regulated a large panel of motor proteins that can be important for wound contraction. Cortisol also suppressed multiple genes involved in wound healing, parts of which were activated by the parasite. Down-regulation of collagens and other structural proteins was in parallel with the induction of proteinases that degrade extracellular matrix (MMP9 and MMP13). Cortisol reduced expression of genes encoding proteins involved in formation of various tissue structures, regulators of cell differentiation and growth factors. Conclusions These results suggest that cortisol-induced stress does not affect the level of infection of Atlantic salmon with the parasite, however, it may retard repair of skin. The cortisol induced changes are in close concordance with the existing concept of wound healing cascade.
In this multi-level investigation, resilience in adaptive functioning among maltreated and nonmaltreated low-income children (N = 677) was examined in relation to the regulation of two stress-responsive adrenal steroid hormones, cortisol and dehydroepiandosterone (DHEA), as well as the personality constructs of ego resiliency and ego control. Maltreatment status was not related to differences in average levels of morning or afternoon cortisol or DHEA. However, lower morning cortisol was related to higher resilient functioning, but only in nonmaltreated children. In contrast, among physically abused children, high morning cortisol was related to higher resilient functioning. Morning and afternoon DHEA was negatively related to resilient functioning. Although diurnal change in cortisol was not related to resilience, for DHEA, maltreated children with high resilience showed an atypical rise in DHEA from morning to afternoon. Morning and afternoon cortisol/DHEA ratios were positively related to resilient functioning, but did not interact with maltreatment status. Ego resiliency and ego control strongly differentiated maltreated and nonmaltreated children, and the personality variables were substantially predictive of resilience. When considered together, demonstrated effects of personality, cortisol, and DHEA maintained independent contributions in predicting resilience among high-risk youth.
Cicchetti, Dante; Rogosch, Fred A.
This study reports acute and sub-chronic effects of cathinone on hormonal alterations in single-caged vervet monkeys. Fourteen adult vervet monkeys were used, 12 of which were treated and 2 controls. Pre-treatment phase of 1 month aimed at establishing baseline levels of hormones while treatment phase of 4 months considered the dose- and time-response effects of cathinone on serum cortisol and prolactin levels. Test animals were allocated four groups of three animals each and administered 0.8, 1.6, 3.2 and 6.4 mg/kg body weight of cathinone orally while controls were administered normal saline. Treatment was done at alternate days of each week. Serum prolactin and cortisol immunoassays were done. Hormonal data was analysed by repeated measures ANCOVA. Results indicate a dose [F (4, 8)?=?218, P?0.001] and time [F (18, 142)?=?21.7, P?0.001] dependent effect of cathinone on cortisol levels with a significant dose by week interaction [F (71, 142)?=?4.86, P?0.001]. Similarly, there was a decrease in serum prolactin [F (4, 8)?=?267, P?0.001] with escalating doses of cathinone with a significant dose x week interaction [F (59, 118)?=?13.03, P?0.001]. The findings demonstrate that at high doses and long-term exposure, cathinone causes hormonal alterations probably via changes in hypothalamo-hypophyseo-adrenocortical and gonadal axes integrity. PMID:24190428
Nyongesa, Albert W; Oduma, Jemimah A; Nakajima, Motohiro; Odongo, Hesbon O; Adoyo, Pius A; al'Absi, Mustafa
Objective The aim of this study was to examine the effect of acute tobacco abstinence on cortisol levels in regular smokers, and whether abstinence-induced changes in cortisol levels are correlated with various signs and symptoms of the tobacco withdrawal syndrome. Methods Smokers (N = 77, ?15 cigarettes/day) attended two counterbalanced sessions (avg = 1 h), one following 12–20 h of abstinence and the other following ad lib smoking. At both sessions, salivary cortisol levels were measured at three time points. Additionally, a battery of self-report questionnaires, physiological assessments, and cognitive performance tasks were administered to measure signs and symptoms of tobacco withdrawal. Results Salivary cortisol levels were significantly lower during the abstinent session versus the non-abstinent session. No significant associations were found between abstinence-induced changes in cortisol and other tobacco withdrawal measures, although there was suggestive evidence that abstinence-induced changes in cortisol levels and hunger were inversely associated to a modest degree. Conclusion Acute tobacco abstinence was associated with decreased cortisol levels. Cortisol dampening during acute tobacco abstinence may reflect nicotine-mediated modulation of hypothalamic–pituitary–adrenal axis activity, which may be relevant to the maintenance of tobacco dependence. Tobacco-withdrawal cortisol changes do not appear to be a cause or consequence of many manifestations of acute tobacco withdrawal with the possible exception of hunger.
Wong, Jordan A.; Pickworth, Wallace B.; Waters, Andrew J.; al'Absi, Mustafa; Leventhal, Adam M.
Circadian rhythm characteristics in healthy male and female humans were studied at 4-hour intervals for urine volume, cortisol, 5-hydroxyindoleacetic acid (5-HIAA), Na, K, Na/K ratios in the urine, as well as plasma cortisol. While plasma and urinary cortisol rhythms were very similar in both sexes, the described rhythms in urine volume, electrolyte, and 5-HIAA excretion differ for the two sexes. The results suggest that sex differences exist in the circadian patterns of important hormone and metabolic functions and that the internal synchrony of circadian rhythms differs for the two sexes. The results seem to indicate that the rhythmical secretion of cortisol does not account for the pattern of Na and K excretion.
Vernikos-Danellis, J.; Winget, C. M.; Goodwin, A. E.; Reilly, T.
The physiological function of 5-HT7 receptors is not yet fully determined. This study was designed to characterize the involvement of 5-HT7 receptor in rat body temperature regulation and in adrenocorticotropic hormone (ACTH) and corticosterone secretion. In the first part of our study, acute administration of SB-269970 (0.1–1mg\\/kg, i.p.), a potent and selective 5-HT7 receptors antagonist, dose-dependently prevented 5-HT1A\\/7 receptor agonist
Céline Faure; Ouissame Mnie-Filali; Hélène Scarna; Guy Debonnel; Nasser Haddjeri
Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (?=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (?=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (?=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (?=0.36; 95% CI: 0.32-0.40), bedtime cortisol (?=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure. PMID:23890985
Golden, Sherita Hill; Sánchez, Brisa N; Wu, Meihua; Champaneri, Shivam; Diez Roux, Ana V; Seeman, Teresa; Wand, Gary S
To verify availability of skin conductance (SC) as an indicator for the sympathetic nervous system (SNS) activity in dogs, the changes in SC and blood levels of stress-related hormones induced by drugs were compared. SC and cortisol, adrenaline and noradrenaline levels were measured in 5 dogs on 4 occasions with or without drug-induced sedation at 7-day intervals (no treatment, intramuscular medetomidine 0.01 mg/kg, intramuscular acepromazine 0.1 mg/kg and intravenous fentanyl 0.02 mg/kg). The fentanyl treatment produced significantly higher levels of SC and plasma cortisol and adrenaline compared with the other 3 treatments. The plasma noradrenaline level also tended to be higher following the fentanyl treatment. These results indicate that SC may reflect changes in the SNS activities in dogs. PMID:23358494
Ishibashi, Maki; Akiyoshi, Hideo; Iseri, Toshie; Ohashi, Fumihito
Rationale Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity\\u000a to stress.\\u000a \\u000a \\u000a \\u000a Objectives We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans.\\u000a As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function.\\u000a \\u000a \\u000a \\u000a Materials and methods Fifty healthy young men received a
Ulrike Rimmele; Maria Spillmann; Carmen Bärtschi; Oliver T. Wolf; Cora S. Weber; Ulrike Ehlert; Petra H. Wirtz
Objectives The objective of this study was to examine the association between cortisol response to mental stress and high-sensitivity cardiac troponin T (hs-cTnT) in healthy older individuals without history of cardiovascular disease (CVD). Background Mental stress is a recognized risk factor for CVD, although the mechanisms remain unclear. Cortisol, a key stress hormone, is associated with coronary atherosclerosis and may accentuate structural and functional cardiac disease. Methods This cross-sectional study involved 508 disease-free men and women aged 53 to 76 years drawn from the Whitehall II epidemiological cohort. We evaluated salivary cortisol response to standardized mental stress tests (exposure) and hs-cTnT plasma concentration using a high-sensitivity assay (outcome). We measured coronary calcification using electron-beam dual-source computed tomography and Agatston scores. Results After adjustment for demographic and clinical variables associated with CVD as well as for inflammatory factors, we found a robust association between cortisol response and detectable hs-cTnT (odds ratio [OR]: 3.98; 95% confidence interval [CI]: 1.60 to 9.92; p = 0.003). The association remained when we restricted the analysis to participants without coronary calcification (n = 222; OR: 4.77; 95% CI: 1.22 to 18.72; p = 0.025) or when we further adjusted for coronary calcification in participants with positive Agatston scores (n = 286; OR: 7.39; 95% CI: 2.22 to 26.24; p = 0.001). Conclusions We found that heightened cortisol response to mental stress was associated with detectable plasma levels of cTnT using high-sensitivity assays in healthy participants, independently of coronary atherosclerosis. Further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage.
Lazzarino, Antonio I.; Hamer, Mark; Gaze, David; Collinson, Paul; Steptoe, Andrew
1 Treatment of eight healthy males with propranolol (80 mg twice daily) for 6 weeks resulted in a significant reduction in overnight plasma levels of prolactin and LH. 2 Plasma testosterone levels were elevated whilst GH and cortisol were unchanged by such treatment. 3 Measurement of overnight hormone levels 48 h after discontinuing treatment showed no evidence of a 'rebound' phenomenon. 4 Cortisol, GH, prolactin, and testosterone plasma levels all showed time dependent changes: propranolol treatment significantly altered the time course of cortisol but not of the other hormones. 5 The effects of chronic propranolol treatment are discussed in terms of a probable direct central action of the drug. In addition the lowered plasma prolactin levels may directly contribute to the hypotensive action of propranolol.
Dart, A M; Lewis, M J; Groom, G V; Meek, E M; Henderson, A H
Depression, type 2 diabetes (T2D), and metabolic syndrome (MetS) are often comorbid. Depression per se increases the risk for T2D by 60%. This risk is not accounted for by the use of antidepressant therapy. Stress causes hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, by triggering the hypothalamic corticotropin-releasing hormone (CRH) secretion, which stimulates the anterior pituitary to release the adrenocorticotropin hormone (ACTH), which causes the adrenal secretion of cortisol. Depression is associated with an increased level of cortisol, and CRH and ACTH at inappropriately “normal” levels, that is too high compared to their expected lower levels due to cortisol negative feedback. T2D and MetS are also associated with hypercortisolism. High levels of cortisol can impair mood as well as cause hyperglycemia and insulin resistance and other traits typical of T2D and MetS. We hypothesize that HPA axis hyperactivation may be due to variants in the genes of the CRH receptors (CRHR1, CRHR2), corticotropin receptors (or melanocortin receptors, MC1R-MC5R), glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), and of the FK506 binding protein 51 (FKBP5), and that these variants may be partially responsible for the clinical association of depression, T2D and MetS. In this review, we will focus on the correlation of stress, HPA axis hyperactivation, and the possible genetic role of the CRHR1, CRHR2, MCR1–5, NR3C1, and NR3C2 receptors and FKBP5 in the susceptibility to the comorbidity of depression, T2D, and MetS. New studies are needed to confirm the hypothesized role of these genes in the clinical association of depression, T2D, and MetS.
Participation in electoral politics is affected by a host of social and demographics variables, but there is growing evidence that biological predispositions may also play a role in behavior related to political involvement. We examined the role of individual variation in hypothalamic-pituitary-adrenal (HPA) stress axis parameters in explaining differences in self-reported and actual participation in political activities. Self-reported political activity, religious participation, and verified voting activity in U.S. national elections were collected from 105 participants, who were subsequently exposed to a standardized (nonpolitical) psychosocial stressor. We demonstrated that lower baseline salivary cortisol in the late afternoon was significantly associated with increased actual voting frequency in six national elections, but not with self-reported non-voting political activity. Baseline cortisol predicted significant variation in voting behavior above and beyond variation accounted for by traditional demographic variables (particularly age of participant in our sample). Participation in religious activity was weakly (and negatively) associated with baseline cortisol. Our results suggest that HPA-mediated characteristics of social, cognitive, and emotional processes may exert an influence on a trait as complex as voting behavior, and that cortisol is a better predictor of actual voting behavior, as opposed to self-reported political activity. PMID:24835544
French, Jeffrey A; Smith, Kevin B; Alford, John R; Guck, Adam; Birnie, Andrew K; Hibbing, John R
Bovine adrenal zona fasciculata (AZF) cells express a noninactivating K 1 current (I AC ) that is inhib- ited by adrenocorticotropic hormone and angiotensin II at subnanomolar concentrations. Since I AC appears to set the membrane potential of AZF cells, these channels may function critically in coupling peptide receptors to membrane depolarization, Ca 2 1 entry, and cortisol secretion. I
John J. Enyeart; Juan Carlos Gomora; Lin Xu; Judith A. Enyeart
Evaluated the susceptibility of radioimmunoassays (RIA) for saliva cortisol to interference effects caused by oral stimulants (drink mix crystals) used to facilitate saliva collection in studies with children. Found that oral stimulants artificially inflated estimated cortisol concentrations, with the magnitude of the interference-effect…
Schwartz, Eve B.; Granger, Douglas A.; Susman, Elizabeth J.; Gunnar, Megan R.; Laird, Brandi
Children with chronic renal insufficiency have a normal diurnal rhythm and normal nocturnal values for serum cortisol when determined by competitive protein binding. Falsely raised values were obtained when a fluorimetric technique was used for the cortisol determination in these patients. Images FIG. 1
Betts, P R; Howse, P M; Morris, R; Rayner, P H
Summary This study was performed to determine the endocrinological starting point of parturition in ewes and to study correlations between the viability of offspring and the concentrations of faecal cortisol metabolites in the dam using 11- oxoetiocholanolone EIA (measuring 11,17- dioxoandrostanes). The levels of faecal cortisol metabolites of 10 ewes positive for ovine pulmonary adenocarcinoma (OPA) were compared against 10
Emanuela Rossi; Domenico Robbe; Paolo Dalla Villa; Angelo Giammarino; Raffaele Luigi Sciorsci
This paper's primary objective is to analyse the physiological (cortisol) and behavioral responses of military working dogs (MWD). Dogs (N=27) were submitted twice to environmental challenges (challenge 1 and 2, 20 days in-between) composed of social (training), visual (mobile toy car) and auditory (air blast) stimuli. Cortisol levels decreased back to the baseline after the second challenge. The behavioral observations showed
A. Haverbeke; C. Diederich; E. Depiereux; J. M. Giffroy
Examined relations between reactivity (peak response) and regulation (response dampening) in 6-month-olds' cortisol and behavioral responses to inoculation. Found that reactivity and regulation were unrelated for both cortisol and behavior, suggesting both measures are needed to characterize more accurately infant response to stress. Found…
Ramsay, Douglas; Lewis, Michael
The relationship of salivary testosterone and cortisol concentrations to personality, criminal violence, prison behavior, and parole board decisions was examined among 113 late-adolescent male offenders. Offenders high in testosterone committed more violent crimes, were judged more harshly by the parole board, and violated prison rules more often than those low in testosterone. No main effects for cortisol emerged. However, as
James M. Dabbs; Gregory J. Jurkovic; Robert L. Frady
This article descibes an ethical experimental module of human biological parameters. The enzyme immunoassay (EIA) kit measures human salivary cortisol levels, which can rise due to circadian and environmental changes. This easy to use sampling kit is described as an ideal procedure for students in behavioral neurobiology or physiological psychology laboratory class to examine cortisol levels.
Brian A. Kalman, Ruth E. Grahn (Conneticut College;)
The current study is one of the first prospective examinations of longitudinal associations between observed father caregiving behaviors and child cortisol reactivity and regulation in response to emotional arousal. Observations of father and mother caregiving behaviors and child cortisol levels in response to challenges at 7 months and 24 months…
Mills-Koonce, W. Roger; Garrett-Peters, Patricia; Barnett, Melissa; Granger, Douglas A.; Blair, Clancy; Cox, Martha J.
Recent studies of the function of adrenal “incidentalomas” have revealed that a proportion of those tumors secrete cortisol insufficiently to produce overt clinical Cushing s syndrome, but that their autonomous cortisol production can suppress the hypothalamo-pituitaryadrenal (HPA) axis to various degrees; this needs to be recognized to avoid acute adrenal insufficiency after adrenalectomy. Several diagnostic approaches have been utilized to
Hélène Lavoie; André Lacroix
Child maltreatment increases the risk for impaired social functioning and cortisol regulation. However, the longitudinal interplay among these factors is still unclear. This study aimed to shed light on the effect of maltreatment on social functioning and cortisol regulation over time. The sample consisted of 236 children (mean age 7.64 years, SD…
Alink, Lenneke R. A.; Cicchetti, Dante; Kim, Jungmeen; Rogosch, Fred A.
The aim of this investigation was to study the action of enkephalins on changes in hormonal-metabolic constants in stress of varied severity. Catecholamine excretion with the urine was determined fluorometrically, serum cortisol and insulin concentrations were measured radioimmunologically and glucose was determined by the standard orthotoluidine method. The results of the investigation indicate that enkephalins have a modulating effect on
Yu. B. Lishmanov; T. V. Lasukova; L. A. Alekminskaya
This study was designed to assess the effects of hypohydration (-5% body weight) and heat acclimation on plasma cortisol and growth hormone responses to exercise (1.34 m/sec -1) in a thermoneutral (20 C, 40% rh), hot-wet (35 C, 79% rh), or hot-dry (49 deg...
K. B. Pandolf M. N. Sawka R. P. Francesconi
Lifetime contaminant and hormonal profiles have been reconstructed for an individual male blue whale (Balaenoptera musculus, Linnaeus 1758) using the earplug as a natural aging matrix that is also capable of archiving and preserving lipophilic compounds. These unprecedented lifetime profiles (i.e., birth to death) were reconstructed with a 6-mo resolution for a wide range of analytes including cortisol (stress hormone), testosterone (developmental hormone), organic contaminants (e.g., pesticides and flame retardants), and mercury. Cortisol lifetime profiles revealed a doubling of cortisol levels over baseline. Testosterone profiles suggest this male blue whale reached sexual maturity at approximately 10 y of age, which corresponds well with and improves on previous estimates. Early periods of the reconstructed contaminant profiles for pesticides (such as dichlorodiphenyltrichloroethanes and chlordanes), polychlorinated biphenyls, and polybrominated diphenyl ethers demonstrate significant maternal transfer occurred at 0–12 mo. The total lifetime organic contaminant burden measured between the earplug (sum of contaminants in laminae layers) and blubber samples from the same organism were similar. Total mercury profiles revealed reduced maternal transfer and two distinct pulse events compared with organic contaminants. The use of a whale earplug to reconstruct lifetime chemical profiles will allow for a more comprehensive examination of stress, development, and contaminant exposure, as well as improve the assessment of contaminant use/emission, environmental noise, ship traffic, and climate change on these important marine sentinels.
Trumble, Stephen J.; Robinson, Eleanor M.; Berman-Kowalewski, Michelle; Potter, Charles W.; Usenko, Sascha
The release of hypothalamic-pituitary-adrenocortical hormones was studied in intact and neutered gray wolves (Canis lupus) to determine how these hormones interact and affect reproductive hormones. Experiments were performed on adult wolves anesthetized with 400 mg ketamine and 50 mg promazine. Intravenous (i.v.) injections with 50 micrograms ovine corticotropin releasing factor (oCRF) significantly increased adrenocorticotropin (ACTH; P < or = 0.01), cortisol (CORT; P < or = 0.004), and progesterone (P < or = 0.036), but not beta-endorphin (P > or = 0.52). Since neutered wolves demonstrated dose-dependent elevations in response to ACTH, it was concluded that the progesterone was secreted from the adrenal gland. Basal luteinizing hormone (LH) concentrations in neutered wolves were similar before and 60 min after i.v. injection of 1, 5, or 25 IU ACTH (P > or = 0.36) or 2.2 mg/kg cortisol (P = 0.42). Neither 25 IU ACTH (P = 0.55) nor 0.22 mg/kg dexamethasone (P = 0.49) altered the LH response to injection of LH releasing hormone in neutered wolves. Chronic administration of 0.22 mg/kg/day dexamethasone for 3 d did not alter baseline LH concentrations (P = 0.75). Injection of 1.0 mg/kg naloxone (NAL), however, increased LH concentrations relative to baseline values in both intact (P = 0.032) and neutered (P = 0.0005) female wolves, but not in intact (P = 0.19) or neutered males (P = 0.07). These results indicated that in gray wolves (1) oCRF stimulated the release of pituitary and adrenal hormones in a fashion similar to that of other mammals; (2) the adrenal cortex was capable of secreting progesterone into the systemic circulation; (3) exogenous glucocorticoids did not alter LH concentrations; and (4) endogenous opioids may modulate LH secretion in female wolves. PMID:1333004
Kreeger, T J; Seal, U S; Plotka, E D
The effect of common husbandry conditions (crowding, social environment, water quality, handling, and background color) on the cortisol stress response in adult zebrafish, Danio rerio, was investigated to check the usefulness of zebrafish as a model organism in aquaculture research. In addition, a noninvasive methodology for assessing stress was evaluated. Zebrafish showed a fast cortisol response with high values at 30 min that returned to basal levels within 2 h of poststress. There was a significant positive correlation between trunk cortisol concentrations and the free water cortisol rate (r(2)=0.829-0.850, p<0.001), indicating that measurement of the water-borne cortisol release rate may serve as a noninvasive and reliable stress indicator at the population level. Crowding resulted in 13- to 21-fold greater mean trunk cortisol concentrations compared with controls. However, even at low stocking density (2-5 fish/L), the maintenance cost was higher than the one at higher densities (10 fish/L) due to the formation of dominance hierarchies. The background color affected trunk cortisol concentrations, with fish exposed to brighter backgrounds (green and white) showing 3- to 8-fold greater mean trunk cortisol concentrations than fish exposed to a black background or transparent aquaria. Fish exposed to high stocking densities for 2 h or 5 days had similar high mean trunk cortisol levels, indicating that exposure of fish for the period of 2 h to a specific stressor may represent a chronic situation in zebrafish. It is concluded that adult laboratory zebrafish had a preference for a transparent or black background aquarium, at a number of 10 individuals per 2 L of available water volume, to express their normal behavior and avoid increased cortisol stress reaction. PMID:23886279
Pavlidis, Michail; Digka, Nikoletta; Theodoridi, Antonia; Campo, Aurora; Barsakis, Konstantinos; Skouradakis, Gregoris; Samaras, Athanasios; Tsalafouta, Alexandra
GH-releasing peptides (GHRPs), a class of small synthetic peptide and non-peptide compounds, act on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in both humans and other animals. GHRPs, like corticotropin-releasing hormone (CRH), also possess acute ACTH- and cortisol-releasing activity, although the mechanisms underlying the stimulatory effect of GHRPs on the hypothalamo-pituitary-adrenal (HPA) axis
A E Rigamonti; S M Bonomo; S G Cella; E E Müller
In this research we examined biological and behavioural correlates of handedness in free-ranging adult male rhesus macaques (Macaca mulatta). Specifically, we examined relationships between handedness and cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma concentrations of the hormones cortisol and adrenocorticotropin (ACTH), and multiple indices of social behaviour, including occurrences
G. C. Westergaard; T. J. Chavanne; I. D. Lussier; L. Houser; A. Cleveland; S. J. Suomi; J. D. Higley
We recently found increased adrenal cortisol responses to adrenocorticotropic hormone (ACTH)1–24 and increased pituitary ACTH and adrenal cortisol responses to corticotropin-releasing factor in premenopausal women with chronic post-traumatic stress disorder (PTSD) compared to healthy nontraumatized subjects. This pattern of hypothalamic–pituitary–adrenal axis (HPA) hyper-reactivity has been previously seen in healthy individuals treated with the antiglucocorticoid mifepristone. We therefore investigated whether endogenous
Ann M Rasmusson; Jitka Vasek; Deborah S Lipschitz; Dolores Vojvoda; Mary Ellen Mustone; Quihu Shi; Gretchen Gudmundsen; Charles A Morgan; Jessica Wolfe; Dennis S Charney
We studied the suppressibility of cortisol secretion in 15 patients with Cushing's disease by measuring morning plasma cortisol level as well as the 24-hour urinary free corisol (UFC) excretion following single doses of increasing amounts of dexamethasone (ranging from 0.5 to 32 mg) given at 11 p.m. The mean plasma cortisol level in patients with Cushing's disease was twice as high as in normal subjects, whereas the mean UFC in these patients was 6 times as high. Plasma cortisol in seven patients were suppressed by less than 4 mg of dexamethasone (in 2 cases, less than 0.5 mg; in 3 cases, less than 2 mg; and in 2 cases less than 4 mg). In these cases, basal plasma cortisol and UFC were less than 25 micrograms/dl and 350 micrograms/day, respectively. Among the other eight patients, plasma cortisol was partially suppressed in 5 cases and not suppressed in 3 cases by high doses of dexamethasone (16-32 mg). In these cases the basal plasma cortisol and UFC were more than 25 micrograms/dl and 350 micrograms/day, respectively. There was a significant correlation between the basal plasma cortisol and UFC (r = 0.687, p less than 0.01). These data suggest that the suppression by increasing amounts of dexamethasone in most cases with Cushing's disease was related to the severity of hypercortisolism. PMID:3250858
Odagiri, E; Demura, R; Demura, H; Suda, T; Ishiwatari, N; Abe, Y; Jibiki, K; Shizume, K
Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 micro g/dl and in thyroid-stimulating hormone (TSH) of 4 microunits ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.
Leach, C. S.; Johnson, P. C.; Driscoll, T. B.
A primary culture system of rainbow trout gill pavement cells grown on permeable support (single-seeded insert, SSI) was used\\u000a to examine histological and physiological changes induced by the addition of the corticosteroid hormone cortisol. Pavement\\u000a cell epithelia were cultured under symmetrical conditions (L15 apical\\/L15 basolateral) and developed a high transepithelial\\u000a resistance (TER, 6.84 ± 1.99 k? cm2, mean ± SEM) with a low phenol red diffusion
Adolf Michael Sandbichler; Julia Farkas; Willi Salvenmoser; Bernd Pelster
Dietary chromium(III) picolinate (CrPic) effects on circulating steroid hormones have been reported in various experimental\\u000a animals. However, direct effects of CrPic on adrenocortical steroidogenesis are uncertain. Therefore, the objective was to\\u000a determine the effects of CrPic on cortisol and dehydroepiandrosterone sulfate (DHEAs) secretion from H295R cells. In experiment\\u000a 1, a 24-h exposure to CrPic (0 to 200 ?M) had both linear
Beob G. Kim; Julye M. Adams; Brian A. Jackson; Merlin D. Lindemann
Rationale Individuals with a family history of alcoholism may present a dysfunction in the activity of the hypothalamic–pituitary–adrenal\\u000a (HPA) axis that predates the development of alcoholism.\\u000a \\u000a \\u000a \\u000a Objective The present study investigated the hypothesis that this HPA-axis dysfunction is associated with alterations in the pattern\\u000a of the circadian (24 h) secretions of adrenal corticotropic hormone (ACTH), cortisol, and ?-endorphin.\\u000a \\u000a \\u000a \\u000a Methods Men with [high risk (HR)
Christina Gianoulakis; Xing Dai; Joseph Thavundayil; Thomas Brown
Transplantation of endocrine cells, especially when protected from immune destruction, is an attractive alternative to whole organ transplantation. The current treatment for adrenal insufficiency whether congenital or acquired is hormone replacement, which is not considered fully physiological. In this study, we isolated porcine adrenal cortical cells by collagenase digestion. The cells were microencapsulated in alginate-polylysine-alginate membranes using electrostatic droplet generator. In vitro, ACTH stimulation of both free and microencapsulated adrenal cortical cells produced comparable cortisol response. It can be concluded that the microencapsulation process is not injurious to the adrenal cortical cells and that it does not hamper their secretory function. PMID:8050809
Abobakr, A M
In order to grade motion sickness objectively, the following 11 adrenal hormones were investigated in subjects with different motion sickness susceptibility: Aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-OH-progesterone, 11-deoxycortisol, cortisol, cortisone, testosterone, androstendione, dehydroepiandrosterone sulfate. Motion sickness was induced by the coriolis effect on a rotary chair. Both severe kinetosis after short rotation time and mild motion sickness after 30 min of rotation occurred together with small hormonal changes. Androstendione and 11-deoxycortisol appear to be sensitive indicators of motion sickness if the rotation time is taken into consideration. A significant increase of all hormones except progesterone, cortisone, testosterone, and dehydroepiandrosterone sulfate was observed when pronounced malaise had come after a long rotation stress (24.6 min). The changes in plasma aldosterone concentration appeared to correlate with time only. The present study demonstrates that hormonal analysis can be helpful in estimating the degree of motion sickness. PMID:4062773
Stalla, G K; Doerr, H G; Bidlingmaier, F; Sippel, W G; von Restorff, W
Two hundred adult male white rats with chronically implanted aortic cannulas were randomly divided into two groups. Animals in the first group were exposed to low-level (1.0 mW/cm2) pulsed-wave 435-MHz radiofrequency radiation (RFR) for approximately 22 h...
C. B. Honeycutt J. C. Toler P. P. Popovic S. J. Bonasera V. P. Popovic
binding to the endogenous murine Dax-1 promoter 10- and 3.5-fold over baseline. Serial ChIP assays reveal that that GR and SF-1 are part of the same complex on the Dax-1 promoter, whereas coimmu- noprecipitation assay confirms the presence of a protein complex that contains both GR and SF-1. ACTH stimulation disrupts the formation of this complex by abrogating SF-1 binding
Brian M. Gummow; Joshua O. Scheys; Victoria R. Cancelli; Gary D. Hammer
Using Northern blotting with a human genomic DNA probe for the pro-opiomelanocortin (POMC) gene, we have shown specific mRNA in normal human peripheral mononuclear cells (PBMC); the presence of specific mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We then demonstrated that PBMC translate the message into protein. Thus, using a radioimmunoassay with an antibody for ACTH, a median of 29 pg of ACTH-like immunoreactivity (ACTH-LIR) was found in 10(7) PBMC. ACTH-LIR was also detected in seven different cell lines derived from patients with lymphoid and myeloid malignancies, two of them JM and U937 showing the highest values 135 and 108 pg/10(7) cells, respectively. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH with molecular weights of the order of 31,000 POMC, 22,000 ACTH, and 4,500 ACTH, in addition to high-molecular-weight material (greater than 43,000). We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator in a similar way to lymphokines and/or may signal the adrenal gland to secrete glucocorticoids. Images
Buzzetti, R; McLoughlin, L; Lavender, P M; Clark, A J; Rees, L H
To better interpret previously described hormonal changes observed during the natural postweaning fast (2-3 months) endured by pups of the northern elephant seal (Mirounga angustirostris), we compared plasma cortisol, thyroid hormones, and leptin in pups (n=5) measured during nursing and fasting periods. Blood samples were taken at four times; early (9 days postpartum) and late (18-22 days postpartum) nursing, and early (second week postweaning) and late (eighth week postweaning) fasting. Plasma cortisol increased 39% between early and late nursing and almost 4-fold by late fasting. After the early nursing period, cortisol and body mass were negatively correlated (y=28.3-0.19 x; R=0.569; p=0.027). Total thyroxine (tT(4)), free T(4) (fT(4)), total triiodothyronine (tT3) and reverse T(3) (rT(3)) were greatest at early nursing and reduced by late nursing and remained so throughout the fast, with the exception of tT(4), which increased between late nursing (17.7+/-2.1 ng mL(-1)) and late fasting (30.1+/-2.8 ng mL(-1)) periods. Leptin remained unaltered among the four sampling periods and was not correlated with body mass. Pups appear to exhibit a shift in the relationship between cortisol and body mass suggesting a potential role for cortisol in the regulation of body fat. The higher concentrations of tT(3) and tT(4) during early nursing may reflect enhanced growth and development during this period, however the increase late in fasting is likely physiologically insignificant and an artifact of reduced metabolic clearance of these hormones. Transition of the pups from nursing to fasting states is characterized by a striking lack of change in cortisol, thyroid hormones, and leptin suggesting that any metabolic alterations associated with this transition may occur independent of these hormones.
Ortiz, Rudy M.; Houser, Dorian S.; Wade, Charles E.; Ortiz, C. Leo
Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.
Sudheimer, Keith D.; O'Hara, Ruth; Spiegel, David; Powers, Bevin; Kraemer, Helena C.; Neri, Eric; Weiner, Michael; Hardan, Antonio; Hallmayer, Joachim; Dhabhar, Firdaus S.
Child maltreatment increases the risk for impaired social functioning and cortisol regulation. However, the longitudinal interplay among these factors is still unclear. This study aimed to shed light on the effect of maltreatment on social functioning and cortisol regulation over time. The sample consisted of 236 children (mean age 7.64 years, SD = 1.36; 125 maltreated children and 111 nonmaltreated children, 128 boys and 108 girls) who attended a week-long summer camp for 2 consecutive years. Saliva was collected during 5 days at 9:00 a.m. and 4:00 p.m. Means of morning and afternoon cortisol levels and cortisol change (difference between morning and afternoon levels, controlled for morning levels) were used to group the children into low-, medium-, and high-cortisol groups. Prosocial, disruptive/aggressive, and withdrawn behaviors were assessed using information from peers and counselors. Maltreated children showed less prosocial and more disruptive/aggressive and withdrawn behavior. Results of structural equation modeling analyses indicated that there were indirect effects of maltreatment on Year 2 morning cortisol via prosocial and disruptive/aggressive behavior: Lower levels of prosocial behavior and higher levels of disruptive/aggressive behavior were related to lower morning cortisol levels 1 year later. Withdrawn behavior was related to higher afternoon cortisol values 1 year later. Results of this study suggest that maltreated children are more likely to experience difficulties in social functioning, which in turn is related to cortisol regulation 1 year later. This altered hypothalamic-pituitary-adrenocortical (HPA) axis functioning may put children at risk for later psychopathology. PMID:21823793
Alink, Lenneke R A; Cicchetti, Dante; Kim, Jungmeen; Rogosch, Fred A
Recent laboratory studies have shown that men display more risk-taking behavior in decision-making tasks following stress, whilst women are more risk-aversive or become more task-focused. In addition, these studies have shown that sex differences are related to levels of the stress hormone cortisol (indicative of activation of the hypothalamus-pituitary-adrenocortical-axis): the higher the levels of cortisol the more risk-taking behavior is shown by men, whereas women generally display more risk-aversive or task-focused behavior following higher levels of cortisol. Here, we assessed whether such relationships hold outside the laboratory, correlating levels of cortisol obtained during a job-related assessment procedure with decision-making parameters in the Cambridge Gambling Task (CGT) in male and female police recruits. The CGT allows for discriminating different aspects of reward-based decision-making. In addition, we correlated levels of alpha-amylase [indicative of activation of the sympatho-adrenomedullary-axis (SAM)] and decision-making parameters. In line with earlier studies men and women only differed in risk-adjustment in the CGT. Salivary cortisol levels correlated positively and strongly with risk-taking measures in men, which was significantly different from the weak negative correlation in women. In contrast, and less strongly so, salivary alpha-amylase levels correlated positively with risk-taking in women, which was significantly different from the weak negative correlation with risk-taking in men. Collectively, these data support and extend data of earlier studies indicating that risky decision-making in men and women is differently affected by stress hormones. The data are briefly discussed in relation to the effects of stress on gambling. PMID:24474909
van den Bos, Ruud; Taris, Ruben; Scheppink, Bianca; de Haan, Lydia; Verster, Joris C
Effects of short-term administration of corticosterone and cortisol on plasma levels of thyroid hormones, gonado-somatic index and testicular histology have been reported in catfish, Clarias gariepinus during different phases of its breeding cycle. Corticosterone administration had no significant effect on plasma levels of T4, T3 and T3/T4 ratio, irrespective of doses and phases of breeding cycle. However, 5 microg dose of cortisol significantly increased plasma levels of T3 and the T3/T4 ratio during quiescent and regressive phases, while it significantly decreased plasma levels of T4 during progressive phase. During breeding phase, 2 microg and 5 microg doses of cortisol significantly decreased plasma levels of T4 and T3, respectively, while 5 microg dose of cortisol alone reduced T3/T4 ratio. Irrespective of phases of annual breeding cycle and doses, short-term administration of corticosterone and cortisol had no significant effect either on GSI or testicular histology. These findings suggest that corticosterone is ineffective in stimulating plasma levels of thyroid hormones, while cortisol, depending on dose and phase/season, may differentially increase, decrease or have no effect on plasma levels of thyroid hormones in C. gariepinus. PMID:22734250
Suchiang, P; Varkey, S; Gupta, B B P
To elucidate the mechanism of insulin resistance due to insulin counterregulatory hormones (ICRHs) and evaluate ICRH secretion kinetics, ICRH concentrations were measured and correlated with blood glucose levels in 28 type 1 diabetic patients. Blood glucose was measured before bedtime. Early morning urine samples were collected the next morning before insulin injection and breakfast. Fasting blood glucose, cortisol, glucagon and HbA1c levels were measured. Growth hormone (GH), adrenaline, cortisol and C-peptide levels in morning urine samples were measured; SD scores were calculated for urine GH. The laboratory values (mean ± SD) were as follows; HbA1c of 8.1% ± 1.4%; pre-bedtime glucose of 203 ± 105 mg/dl; fasting blood glucose of 145 ± 87 mg/dl; serum cortisol of 21.6 ± 5.5 µg/dl; plasma glucagon of 98 ± 41 pg/ml; urinary GH, 27.2 ± 13.0 ng/gCr; urinary cortisol of 238 ± 197 ng/gCr; and urinary Adrenaline of 22.9 ± 21.0 ng/gCr. The mean urinary GH SD score was increased (+1.01 ± 0.70; p=0.000); the mean plasma glucagon lebel (98 ± 41 pg/ml) was not. Fasting blood glucose was positively correlated with plasma glucagon (R=0.378, p=0.0471) and negatively correlated with urinary cortisol (R=–0.476, p=0.010). Urinary adrenaline correlated positively with urinary GH (R=0.470, p=0.013) and urinary cortisol (R=0.522, p=0.004). In type 1 diabetes, GH, glucagon and cortisol hypersecretion may contribute to insulin resistance, but the mechanism remains unclear.
Nishimura, Akiko; Kobayashi, Kisho; Yagasaki, Hideaki; Saito, Tomohiro; Nagamine, Kenjiro; Mitsui, Yumiko; Mochizuki, Mie; Satoh, Kazumasa; Kobayashi, Koji; Sano, Tomoaki; Ohta, Masanori; Cho, Hideo; Ohyama, Kenji
\\u000a Human growth hormone (hGH) is a proteohormone secreted by the pituitary gland. It acts through binding to the hGH receptor,\\u000a inducing either direct effects or initiating the production of insulin-like growth-factor I (IGF-I), the most important mediator\\u000a of hGH effects. Growth hormone is primarily known to promote longitudinal growth in children and adolescents, but has also\\u000a various important metabolic functions
Martin Bidlingmaier; Christian J. Strasburger
Species differences in physiological and biochemical attributes exist even among closely related species and may underlie species-specific sensitivity to toxicants. Rainbow trout (RT) are more sensitive than brook trout (BT) to the teratogenic effects of selenium (Se), but it is not known whether all tissues exhibit this pattern of vulnerability. In this study, primary cultures of RT and BT adrenocortical cells were exposed to selenite (Na(2)SO(3)) and selenomethionine (Se-Met) to compare cell viability and ACTH-stimulated cortisol secretion in the two fish species. Cortisol, the primary stress hormone in fish, facilitates maintenance of homeostasis when fish are exposed to stressors, including toxicants. Cell viability was not affected by Se, but selenite impaired cortisol secretion, while Se-Met did not (RT and BT EC(50)>2000mg/L). RT cells were more sensitive (EC(50)=8.7mg/L) to selenite than BT cells (EC(50)=90.4mg/L). To identify the targets where Se disrupts cortisol synthesis, selenite-impaired RT and BT cells were stimulated with ACTH, dbcAMP, OH-cholesterol, and pregnenolone. Selenite acted at different steps in the cortisol biosynthesis pathway in RT and BT cells, confirming a species-specific toxicity mechanism. To test the hypothesis that oxidative stress mediates Se-induced toxicity, selenite-impaired RT cells were exposed to NAC, BSO and antioxidants (DETCA, ATA, Vit A, and Vit E). Inhibition of SOD by DETCA enhanced selenite-induced cortisol impairment, indicating that oxidative stress plays a role in Se toxicity; however, modifying GSH content of the cells did not have an effect. The results of this study, with two closely related salmonids, provided additional evidence for species-specific differences in sensitivity to Se which should be considered when setting thresholds and water quality guidelines. PMID:21466817
Miller, L L; Hontela, A
Spontaneous prolactin and cortisol patterns were determined at 20 min intervals over 3 hr during the night in eight patients with melancholia, both during illness and after treatment with amitriptyline. Mean plasma prolactin levels were greater after recovery in the seven patients who responded to treatment. Mean cortisol secretion decreased upon recovery from melancholia, and such changes in two patients paralleled normalization of dexamethasone suppression test responses. The influence of assumptions of lack of interaction on the statistical significance of the analysis of variance with repeated measures for prolactin and cortisol values was evaluated. PMID:3659229
Lisansky, J; Fava, G A; Zielezny, M A; Morphy, M A; Kellner, R
Abstract Background: Antiepileptics may affect cortisol metabolism through CYP3A4. There is little known about ethosuximide. Clinical Case: Our patient is a 12-year-old girl with salt-wasting congenital adrenal hyperplasia (CAH) owing to 21 hydroxylase deficiency. A standard treatment regimen was initiated with satisfactory results until the age of 6 years, when she developed absence seizures treated with ethosuximide. She received such therapy until the age of 12 years, at which point ethosuximide was discontinued. During ethosuximide administration, she experienced worsening control of CAH disease activity that responded to progressive increases in hydrocortisone dose up to 28 mg/m2 per day. Despite high doses of hydrocortisone, she suffered no cushingoid symptoms. Her requirements for high glucocorticoid replacement doses resolved shortly after ethosuximide was discontinued. We provide data over 6 years demonstrating a correlation between adrenal hormone secretion, cortisol requirements and ethosuximide dose. Conclusion: This is the first case demonstrating an interaction between ethosuximide and hydrocortisone clearance in the treatment of salt-wasting CAH. PMID:24468605
Yau, Mabel; Rao, Niva; Nimkarn, Saroj; Vogiatzi, Maria
Thyroxine (T(4)) and triiodothyronine (T(3)), the principal thyroid hormones (THs) secreted from the hypothalamic-pituitary-thyroid (HPT) axis, produce a plethora of physiologic actions in fish. The diverse actions of THs in fishes are primarily due to the sensitivity of thyroid axis to many physical, chemical and biological factors of both intrinsic and extrinsic origins. The regulation of THs homeostasis becomes more complex due to extrathyroidal deiodination pathways by which the delivery of biologically active T(3) to target cells has been controlled. As primary stress hormones and the end products of hypothalamic-pituitary-interrenal (HPI) and brain-sympathetic-chromaffin (BSC) axes, cortisol and adrenaline exert its actions on its target tissues where it promote and integrate osmotic and metabolic competence. Despite possessing specific osmoregulatory and metabolic actions at cellular and whole-body levels, THs may fine-tune these processes in accordance with the actions of hormones like cortisol and adrenaline. Evidences are presented that THs can modify the pattern and magnitude of stress response in fishes as it modifies either its own actions or the actions of stress hormones. In addition, multiple lines of evidence indicate that hypothalamic and pituitary hormones of thyroid and interrenal axes can interact with each other which in turn may regulate THs/cortisol-mediated actions. Even though it is hard to define these interactions, the magnitude of stress response in fish has been shown to be modified by the changes in the status of THs, pointing to its functional relationship with endocrine stress axes particularly with the interrenal axis. The fine-tuned mechanism that operates in fish during stressor-challenge drives the THs to play both fundamental and modulator roles in stress response by controlling osmoregulation and metabolic regulation. A major role of THs in stress response is thus evident in fish. PMID:21362420
Peter, M C Subhash
This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed, and children's saliva was sampled before, during, and after standardized procedures designed to elicit emotional arousal. Results revealed cocaine-exposed infants had a high amplitude trajectory of cortisol reactivity compared to non-cocaine-exposed infants. Infant gender and caregiving instability moderated this association. The findings support a dual hazard vulnerability model and have implications for evolutionary-developmental theories of individual differences in biological sensitivity to context.