Adrenal Response Research Articles

Cardiac vagal tone, plasma cortisol, and dehydroepiandrosterone response to an ACTH challenge in lame and nonlame dairy cows

We studied the adrenocortical and vagal tone responses to a single ACTH challenge in lame (n = 9) vs nonlame (n = 9) dairy cows. Cows were paired according to parity, days in milk, and milk yield. Plasma cortisol and dehydroepiandrosterone concentrations and cardiac vagal tone response (high-frequency component of heart rate variability) were compared after intravenous ACTH administration. Baseline, minimum or maximum, amplitude of the response and area under the response curve were compared. No difference was detected between groups in the cortisol response. Dehydroepiandrosterone was irresponsive to ACTH treatment, and concentrations did not differ between lame and nonlame cows. Vagal tone decreased in response to the ACTH treatment. High frequency component of heart rate variability was lower in the lame group at all sampling times. Lameness was associated with delayed return to baseline. We concluded that the adrenal response capacity is not influenced by lameness, which supports the concept of lameness being a chronic intermittent rather than a chronically persistent stressor. Dehydroepiandrosterone concentrations were not proven to be useful indicators of hypothalamus–pituitary axis dysfunction in cattle. A decreased vagal contribution to heart rate variability—possibly coupled with increased sympathetic modulation—was observed in lame cows, which suggests that lameness affects the mechanisms underlying the action of ACTH on cardiovascular activity.

Sex- and Stress-Dependent Effects on Dendritic Morphology and Spine Densities in Putative Orexin Neurons

We recently found that non-stressed female rats have higher basal prepro-orexin expression and activation of orexinergic neurons compared to non-stressed males, which lead to impaired habituation to repeated restraint stress at the behavioral, neural, and endocrine level. Here, we extended our study of sex differences in the orexin system by examining spine densities and dendritic morphology in putative orexin neurons in adult male and female rats that were exposed to 5 consecutive days of 30-min restraint. Analysis of spine distribution and density indicated that putative orexinergic neurons in control non-stressed females had significantly more dendritic spines than those in control males, and the majority of these were mushroom spines. This morphological finding may suggest more excitatory input onto orexin neurons in female rats. As orexin neurons are known to promote the hypothalamic–pituitary–adrenal response, this morphological change in orexin neurons could underlie the impaired habituation to repeated stress in female rats. Dendritic complexity did not differ between non-stressed males and females, however repeated restraint stress decreased total dendritic length, nodes, and branching primarily in males. Thus, reduced dendritic complexity of putative orexinergic neurons is observed in males but not in females after 5days of repeated restraint stress. This morphological change might be reflective of decreased orexin system function, which may allow males to habituate more fully to repeated restraint than females. These results extend our understanding of the role of orexin neurons in regulating habituation and demonstrate changes in putative orexin cell morphology and spines that may underlie sex differences in habituation.

Determination of salivary cortisol to assess time-related changes of the adrenal response to stress in critically ill patients

BackgroundThe value of salivary cortisol measurement to study stress-related adrenal response is controversial. The study aim was to assess the role of salivary cortisol measurement to detect time-related changes of adrenal response in critically ill patients. Patients and methodsPatients with organ failure, sepsis or trauma were prospectively recruited in the Emergency Department. Serum and salivary cortisol were measured at baseline (T0) and after 48 h (T48). In 33 patients ACTH test was also done. ResultsFifty-five patients were studied and classified as septic (22) or non-septic (33). We found a significant correlation between serum and salivary cortisol at T0 and T48. No patient had baseline serum cortisol < 276 nmol/L and salivary cortisol significantly decreased at T48 in almost all patients. A delta serum cortisol < 250 nmol/L after ACTH was found in only 4 patients who showed elevated baseline cortisol levels. ConclusionWe found that reduced baseline and post-ACTH cortisol levels are uncommon in our samples. In patients able to provide adequate saliva samples, salivary cortisol may be used to check the degree of stress-induced response and appears as a suitable tool for multiple measurements over time.

Attachment Security Moderates Effects of Uncontrollable Stress on Preadolescent Hypothalamic–Pituitary–Adrenal Axis Responses: Evidence of Regulatory Fit

This study examined whether perceived attachment security (i.e., perceptions of caregivers as responsive, available, and open to communication during times of need) and effortful coping work in concert to buffer against uncontrollable life event effects on hypothalamic–pituitary–adrenal axis (HPA) response patterns in preadolescent boys and girls ( N = 121, mean age = 10.60 years). Children completed the Trier Social Stress Test (TSST) and were immediately thereafter exposed to one of two randomly assigned coping conditions: distraction and avoidance. Piecewise growth multilevel modeling of children’s salivary cortisol levels over the course of the experimental protocol suggested that uncontrollable life events in the year prior were associated with exaggerated cortisol reactivity, though this pattern was buffered against by children’s secure attachment beliefs. Furthermore, perceived attachment security, uncontrollable life event, and coping condition interactive effects on cortisol recovery emerged. As expected, distraction supported efficient cortisol recovery for those uncontrollable stress-exposed children with secure beliefs, and avoidance worked in this fashion for those with insecure beliefs. Findings point to perceived attachment security as a putative buffer of stress-exposed preadolescents’ HPA reactivity and possible contributor to regulatory fit, informing how specific coping skills work or backfire in supporting these children’s HPA recovery efficiency.

Seasonal Changes in Fecal Glucocorticoid Metabolite Concentrations in Bison (Bison bison) Living with or without Wolves (Canis lupus)

The threat of predation can cause increased adrenal secretion of glucocorticoids that, if sustained, can result in chronic stress that might predispose animals to disease, reduced growth, or poor fertility. Fecal glucocorticoid metabolite (FGM) concentrations were measured between September 2011 and July 2012 in two Montana bison (Bison bison) herds, one herd living with and the other without wolves (Canis lupus) in their habitat. The relevance of FGM concentrations (as measured by the corticosterone enzyme immunoassay) and a confirmation of an acute adrenal response was demonstrated by transient increases (P<0.001) in FGM concentrations in bison herded through a chute system and following a wolf encounter. The FGM concentrations were higher in the herd with wolves than the herd without wolves overall (P=0.045), but the monthly differences between the herds were inconsistent (magnitude=0.3-3.5 µg/g; P=0.011 month×herd). The herd with wolves had higher FGM in April, June, July, September, and November, but the herd without wolves had higher FGM in January, February, and May. Seasonal changes in FGM concentrations (P<0.001) were measured across the year in both herds (magnitude=10.8 and 6.9 µg/g, respectively), exceeding any differences between herds potentially attributable to wolf presence. Concentrations of FGM were highest in April-July and were lowest in January-February. Evidence of a chronic stress response was not found, and increased disease susceptibility in the bison living with wolves seems unlikely.

Role of Corticotropin Releasing Factor in the Neuroimmune Mechanisms of Depression: Examination of Current Pharmaceutical and Herbal Therapies.

Approximately 3% of the world population suffers from depression, which is one of the most common form of mental disorder. Recent findings suggest that an interaction between the nervous system and immune system might be behind the pathophysiology of various neurological and psychiatric disorders, including depression. Neuropeptides have been shown to play a major role in mediating response to stress and inducing immune activation or suppression. Corticotropin releasing factor (CRF) is a major regulator of the hypothalamic pituitary adrenal (HPA) axis response. CRF is a stress-related neuropeptide whose dysregulation has been associated with depression. In this review, we summarized the role of CRF in the neuroimmune mechanisms of depression, and the potential therapeutic effects of Chinese herbal medicines (CHM) as well as other agents. Studying the network of CRF and immune responses will help to enhance our understanding of the pathogenesis of depression. Additionally, targeting this important network may aid in developing novel treatments for this debilitating psychiatric disorder.

Extra-Adrenal Glucocorticoid Synthesis in the Intestinal Mucosa: Between Immune Homeostasis and Immune Escape.

Glucocorticoids (GCs) are steroid hormones predominantly produced in the adrenal glands in response to physiological cues and stress. Adrenal GCs mediate potent anti-inflammatory and immunosuppressive functions. Accumulating evidence in the past two decades has demonstrated other extra-adrenal organs and tissues capable of synthesizing GCs. This review discusses the role and regulation of GC synthesis in the intestinal epithelium in the regulation of normal immune homeostasis, inflammatory diseases of the intestinal mucosa, and the development of intestinal tumors.

A Long-Acting Neutralizing Monoclonal ACTH Antibody Blocks Corticosterone and Adrenal Gene Responses in Neonatal Rats.

The control of steroidogenesis in the neonatal adrenal gland is of great clinical interest. We have previously demonstrated that the postnatal day (PD) 2 rat exhibits a large plasma corticosterone response to hypoxia in the absence of an increase in plasma ACTH measured by RIA, whereas the corticosterone response to exogenous ACTH is intact. By PD8, the corticosterone response to hypoxia is clearly ACTH-dependent. We hypothesized that this apparently ACTH-independent response to hypoxia in the newborn rat is due to an increase in a bioactive, nonimmunoassayable form of ACTH. To evaluate this phenomenon, we pretreated neonatal rats with a novel, specific, neutralizing anti-ACTH antibody (ALD1611) (20 mg/kg or 1 mg/kg IP) on the morning of PD1, PD7, and PD14. Twenty-four hours later, we measured hypoxia- or ACTH-stimulated plasma ACTH and corticosterone. For long-term effects, ALD1611 was given on PD1 and pups were studied on PD8 and PD15. Pretreatment with ALD1611 significantly decreased baseline corticosterone and completely blocked the corticosterone response to hypoxia and exogenous ACTH stimulation at all ages. The effect of 1 mg/kg ALD1611 on PD1 had dissipated by PD15. The decrease in corticosterone in ALD1611-treated pups was associated with decreases in baseline and hypoxia- and ACTH-stimulated adrenal Ldlr, Mrap, and Star mRNA expression at all ages. The adrenal response to hypoxia in the newborn rat is ACTH-dependent, suggesting the release of nonimmunoassayable, biologically active forms of ACTH. ALD1611 is useful as a tool to attenuate stress-induced, ACTH-dependent adrenal steroidogenesis in vivo.

Role of Epigenetic Mechanisms in Transmitting the Effects of Neonatal Sevoflurane Exposure to the Next Generation of Male, but not Female, Rats

(Br J Anaesth. 2018;121:406–416) Neonatal anesthesia-induced abnormalities and their mechanisms are poorly understood, even in exposed animals. Some studies have shown that rats, especially male rats, develop behavioral deficiencies and exacerbated hypothalamic-pituitary adrenal responses to stress when exposed as neonates to anesthetic. Furthermore, recent studies suggest that these deleterious effects could be carried into the next generation via epigenetic mechanisms (noncoding RNAs, DNA methylation). There is a pressing need for further research, in order to establish safety guidelines for anesthesia in children, The authors of the present study exposed neonatal rats to sevoflurane and evaluated their progeny for inherited behavioral and molecular alterations.

Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals.

BackgroundThe hypothalamic‐pituitary‐adrenal axis regulates the response to sepsis‐associated stress. Relative adrenal insufficiency or adrenocorticotropic hormone (ACTH):cortisol imbalance, defined as a poor cortisol response to administration of ACTH, is common and associated with death in hospitalized foals. However, information on other adrenal steroid response to ACTH stimulation in sick foals is minimal.ObjectiveTo investigate the response of multiple adrenocortical steroids to administration of ACTH in foals.AnimalsHospitalized (n = 34) and healthy (n = 13) foals.MethodsIn this prospective study, hospitalized foals were categorized into 2 groups using cluster analysis based on adrenal steroids response to ACTH stimulation: Cluster 1 (n = 11) and Cluster 2 (n = 23). After baseline blood sample collection, foals received 10 μg of ACTH with additional samples collected at 30 and 90 minutes after ACTH. Steroid and ACTH concentrations were determined by immunoassays. The area under the curve (AUC) and Delta0‐30 were calculated for each hormone.ResultsThe AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α‐OH‐progesterone, and progesterone were higher in critically ill (Cluster 1) compared to healthy foals (P < .01). Delta0‐30 for cortisol and 17α‐OH‐progesterone was lower in Cluster 1 (24%, 26.7%) and Cluster 2 (16%, 11.2%) compared to healthy foals (125%, 71%), respectively (P < .05). Foals that died had increased AUC for endogenous ACTH (269 versus 76.4 pg/mL/h, P < .05) accompanied by a low AUC for cortisol (5.5 versus 15.5 μg/dL/h, P < .05), suggesting adrenocortical dysfunction.Conclusion and Clinical ImportanceThe 17α‐OH‐progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.

RNA-seq analysis of LPS-induced transcriptional changes and its possible implications for the adrenal gland dysregulation during sepsis

Activation of the adrenal gland stress response is of utmost importance to survive sepsis. Experimental and clinical evidence exists demonstrating that adrenal gland often develops functional and structural damage due to sepsis with mechanisms remaining largely unknown. In the present study, we have used RNA Sequencing (RNA-Seq) technology to analyze changes in adrenal transcriptome elucidated by bacterial LPS. We aimed to find particularly alterations in genes that were previously not reported to be involved in the adrenal gland dysregulation in contexts of sepsis. Our results demonstrate that systemic administration of LPS significantly altered expression of 8458 genes as compared to saline injected animals. The subsequent quality and functional analysis of these gene signatures revealed that LPS-induced highly homogenous transcriptional response in total upregulating 4312 and downregulating 4146 genes. Furthermore, functional annotation analysis together with gene enrichment set analysis (GSEA) clearly demonstrated that adrenal response to LPS involved alterations in multiple pathways related to the inflammatory response along with previously unexplored activation of the hypoxia pathway. In addition, LPS strongly downregulated genes involved in the adrenal homeostasis, development, and regeneration. Those alterations were subsequently verified in clinically relevant cecal ligation and puncture (CLP)-induced sepsis model. Collectively, our study demonstrates that RNA-seq is a very useful method that can be applied to search for new unexplored pathways potentially involved in adrenal gland dysregulation during sepsis.

Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia.

The impaired ability of the autonomic nervous system to respond to hypoglycemia is termed “hypoglycemia-associated autonomic failure” (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycemia counterregulation under controlled conditions, hypoglycemia prevention remains the current mainstay therapy for HAAF. Epinephrine-synthesizing neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic neurons that regulate peripheral epinephrine release. Here we determined whether or not C1 and C3 neuronal activation is impaired in HAAF and whether or not 1 wk of hypoglycemia prevention or treatment with naloxone could restore C1 and C3 neuronal activation and improve HAAF. Twenty male Sprague-Dawley rats (250–300 g) were used. Plasma epinephrine levels were significantly increased after a single episode of hypoglycemia (n = 4; 5,438 ± 783 pg/ml vs. control 193 ± 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia (n = 4; 2,179 ± 220 pg/ml vs. 5,438 ± 783 pg/ml, P < 0.05). Activation of medullary C1 (n = 4; 50 ± 5% vs. control 3 ± 1%, P < 0.05) and C3 (n = 4; 45 ± 5% vs. control 4 ± 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 (n = 4; 12 ± 3%, P < 0.05) and C3 (n = 4; 19 ± 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia.

SAT-545 The Response of the Hypothalamic-Pituitary-Thyroid (HPT) Axis to a Palatable Diet or Exercise Depends on Sex and Housing Conditions in Adult Rats

Single housing induces behavioral, neuroendocrine and metabolic alterations. As thyroid hormones (TH) regulate several aspects of metabolism, and HPT axis is modulated by energy status and emotional stress, we evaluated the effect of isolation on HPT axis response to a palatable diet under basal conditions and after an acute stressor as restraint. Weaned female or male rat pups (Wistar) were caged alone (isolated, Iso; n=8) or in groups of 4 (group housed, Gh; n=12) at postnatal day (PND) 22. At adulthood (PND 63), Gh and Iso rats had access to chow or a palatable diet (Pd: peanuts, cookies, chow) for 1 or 3 months and exposed, in the latter, to 1 h of restraint stress (RES). Gh or Iso males and females increased their kcal intake of Pd, inducing white fat (WAT) accumulation (more in females), leptinemia and insulinemia. Pd for1 month increased Trh-degrading enzyme expression in both Gh sexes, and decreased TSH in Gh males. In females, T4 increased in Gh-Pd; TSH and T4 reduced in Iso-Pd rats. After 3 months of Pd, RES activated adrenal axis, but its response was curtailed by Pd in Gh-males, and to a lesser extent in Iso. In Gh-Pd females, corticosterone decreased but not in Iso. RES-induced inhibition of HPT axis was not diminished by Pd in Gh-males, as seen in the adrenal response, on the contrary, it decreased even further to a similar extent as did Iso in Trh expression, TSH and T4 levels; Iso reduced T3 levels independent of diet. In females, the only significant change was an increase in Trh mRNA levels in Iso-chow. Brown adipose tissue (BAT) gene expression was affected in Gh and Iso males by Pd (Adrb3 and Dio2) whereas in females, Dio2 decreased only in Iso-Pd. These results support a differential adrenal and HPT responses due to sex and housing. HPT axis activity increases by energy demands, we thus studied the effect of 2 weeks of voluntary wheel running (WR) in Gh and Iso adult rats. Controls were sedentary (Sed) pair-fed to the amount of food consumed by WR groups. Females ran more than males and, in either sex, Gh and Iso ran equivalently. WR reduced body weight gain in Iso and Gh males, without changes in fat mass. Gh females lost body weight, but not Iso; ovaric and subcutaneous fat decreased in Gh rats, Iso only lost subcutaneous fat. WR diminished PVN Trh mRNA levels and increased serum TSH in female Gh. Iso blunted several TH- and exercise-induced targets in BAT and WAT. WR stimulated BAT expression of Adrb3 and Ucp1 in Gh or Iso males whereas in Iso females, Dio2 and Ucp1. WR increased Adrb3 in WAT of Gh males or females and Pparg in Gh males and in Iso females. These results show the complex and multifactorial modulation of metabolism between males and females. In conclusion, single housing has long-term consequences in metabolism and HPT axis activity, and sex determines the hormonal responses to diet or exercise in adulthood. Grants: PAPIIT-IA200417 (LJH), IN204316 and CONACyT 284883 (PJB)

SUN-424 An Unusual Presentation of Delayed Onset Panhypopituitarism after Cardiac Surgery

Coronary Artery Bypass Grafting (CABG) surgery is identified in case reports as a rare cause of pituitary apoplexy, postulated to be caused by sustained hypotension due to intraoperative extracorporeal circulation. This typically presents with acute neurological manifestations and evidence of pituitary infarction on Magnetic Resonance Imaging (MRI). Here, we present a case of panhypopituitarism without apoplexy weeks after CABG, which presented with nonspecific signs and without definite neuroimaging abnormalities. SM, a 57 year old man with Type 1 Diabetes underwent elective CABG. His initial postoperative course was uneventful. On review at 4 weeks, his sternotomy wound was slow to heal. At 6 weeks, there was wound dehiscence and he was admitted for management of this. He noted a number of significant hypoglycaemic events over the preceding 10 days, despite a 30% reduction in daily insulin over that period. On readmission sodium was reduced at 118mmol/L – normal 6 weeks prior. This was felt to be SIADH secondary to infection, supported by raised urinary sodium and low plasma osmolality. Fluid restriction, however, led to no improvement. He continued to experience hypoglycaemia and erratic glycemic control. Persistent hypotension was then noted, though initially attributed to diuretics. Thyroid function showed low T4 and TSH levels. Panhypopituitarism was confirmed with markedly low Growth Hormone, IGF-1, Prolactin, FSH, LH and 8am cortisol. Adrenal response was absent on short Tetracosactide testing. MRI pituitary was unremarkable. Anterior Pituitary Hormone replacement with Levothyroxine, Hydrocortisone and Somatropin was commenced. Blood pressure improved and electrolytes normalised. 1 year later, SM’s pituitary hormones were maintained within normal ranges with exogenous replacement. However, glycemic control has been challenging, due to loss of counterregulatory hormonal responses to hypoglycaemia. Panhypopituitarism is rarely reported after CABG and mostly involves apoplexy or infarction of a pre-existing pituitary adenoma, with characteristic findings on neuroimaging. These cases relate to alterations in blood flow through the pituitary on ‘bypass’ and highlight the intrinsic vulnerability of the pituitary vasculature. This case is unusual in a number of respects - presentation weeks after surgery with nonspecific findings - poor wound healing and decreased insulin requirements, rather than acute neurological manifestations postoperatively. Previous reports have demonstrated pre-existing pituitary adenomas or evidence of pituitary infarction on MRI. Despite clear biochemical Panhypopituitarism, the MRI here shows a normal gland. Finally, this case reiterates the need for vigilance for subtle and delayed manifestations of pituitary dysfunction post Cardiac Surgery with intervention, prior to life threatening overt glucocorticoid deficiency.

SAT-380 Screening for Central Adrenal Insufficiency in Children with Prader-Willi Syndrome (PWS) with Single Collection Of ACTH and Cortisol Levels

Baseline a.m ACTH and Cortisol levels in Children with Prader-Willi-syndrome are no different from general population. Moris Angulo, MD1 & Mariano Castro-Magaña, MD1 1Dept of Peds, NYU-Winthrop Hospital, New York, NY Background Prader-Willi syndrome (PWS) is a multi-system genetic disorder resulting from the lack of expression of the paternal genes from chromosome 15q11.2-q13 due to paternal deletion, uniparental disomy (UPD) or an imprinting center defect. Many of their features are explained by hypothalamic dysfunction, therefore individuals with PWS are at high risk for pituitary hormonal deficiency. When the pituitary begins to fail, there is generally a specific sequential failure of pituitary hormones, starting with GH, continuing through LH and FSH deficiency, and culminating in loss of TSH and ACTH. Generally, ACTH is the last to be lost. A high prevalence (60%) of central adrenal insufficiency (CAI) however, has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. Many children, including infants have undergone stimulation testing to confirm or rule out CAI. Several studies however, using same test and other different testing methods including insulin tolerance test (ITT), low dose/high dose ACTH stimulation, glucagon stimulation tests have reported differing results with prevalence between 0 to 7·5%. Previous study has shown that basal cortisol is closely correlated with adrenal response to stimulation. Methods: We studied 105 children with genetic diagnosis of PWS, age 2 to__years. (60 males and 45 females) after basal Cortisol and ACTH level collected at 0800 h. Sixty eight children (60 %) had deletion I and II, 24 (23%)UPD and 13 had only positive DNA Methylation testing . All participant were already on GH treatment without illness or any other stressful condition during testing. Results: All had normal morning Cortisol and ACTH level but 2 children, age 2 and 5 years with low and 4 y.o. male with increased cortisol level. These 3 children had normal ACTH level. Repeat sample after a week, revealed normal both Cortisol and ACTH level. Conclusion: suggesting that clinically significant adrenal insufficiency in PWS is rare

Effects of 50 Hz magnetic fields on circadian rhythm control in mice.

Artificial light and power frequency magnetic fields are ubiquitous in the built environment. Light is a potent zeitgeber but it is unclear whether power frequency magnetic fields can influence circadian rhythm control. To study this possibility, 8–12‐week‐old male C57BL/6J mice were exposed for 30 min starting at zeitgeber time 14 (ZT14, 2 h into the dark period of the day) to 50 Hz magnetic fields at 580 μT using a pair of Helmholtz coils and/or a blue LED light at 700 lux or neither. Our experiments revealed an acute adrenal response to blue light, in terms of increased adrenal per1 gene expression, increased serum corticosterone levels, increased time spent sleeping, and decreased locomotor activity (in all cases, P < 0.0001) compared to an unexposed control group. There appeared to be no modulating effect of the magnetic fields on the response to light, and there was also no effect of the magnetic fields alone (in both cases, P > 0.05) except for a decrease in locomotor activity (P < 0.03). Gene expression of the cryptochromes cry1 and cry2 in the adrenals, liver, and hippocampus was also not affected by exposures (in all cases, P > 0.05). In conclusion, these results suggest that 50 Hz magnetic fields do not significantly affect the acute light response to a degree that can be detected in the adrenal response. Bioelectromagnetics. 2019;9999:XX–XX. © 2019 Bioelectromagnetics Society.

Prolactin - a pleiotropic factor in health and disease.

The principal role of prolactin in mammals is the regulation of lactation. Prolactin is ahormone that is mainly synthesized and secreted by lactotroph cells in the anterior pituitary gland. Prolactin signalling occurs via a unique transmembrane prolactin receptor (PRL-R). Thestructure of the PRL-R has now been elucidated and is similar to that of many biologically fundamental receptors of the class 1 haematopoietic cytokine receptor family such as the growth hormone receptor. The PRL-R is expressed in a wide array of tissues, and a growing number of biological processes continue to be attributed to prolactin. In this Review, we focus on the newly discovered roles of prolactin in human health and disease, particularly its involvement in metabolic homeostasis including body weight control, adipose tissue, skin and hair follicles, pancreas, bone, the adrenal response to stress, the control of lactotroph cell homeostasis and maternal behaviour. New data concerning the pathological states of hypoprolactinaemia and hyperprolactinaemia will also be presented and discussed.

Isoflavones Alter Hypothalamic–Pituitary–Adrenal Axis Response Following Photoperiod Alteration

Photoperiod and diet are factors known to modulate the hypothalamic–pituitary–adrenal (HPA) axis. Specifically, shifts in photoperiod have been previously linked with affective and anxiety disorders. Furthermore, isoflavones have been shown to mediate behavioral outcome in response to the environment of the animal. Here, we investigated the effect of photoperiod alteration on the HPA axis and how the addition of isoflavones might modulate the response to stress. Male C57BL/6J mice were maintained on either a 12:12 or a 16:8 light–dark (LD) cycle for 10 days, and fed a diet of either standard rodent chow or an isoflavone free (IF) chow beginning 3 weeks prior to light alteration. Consistent with previous work, mice in the shorter active period (16:8 LD cycle) showed increased basal corticosterone (CORT) secretion. In the absence of isoflavones, this response was attenuated. Increases in mineralcorticoid (MR) and glucocorticoid (GR) receptor mRNA expression were seen in the pituitary following photoperiod alteration. However, animals fed the standard isoflavone rich chow showed increases in the ratio of MR:GR mRNA in the anterior bed nucleus of the stria terminalis following photoperiod alteration. Decreases in corticotrophin-releasing factor receptor 1 (CRFR1) mRNA expression were seen in animals fed the IF chow in the amygdala, prefrontal cortex and ventral hippocampus. These data suggest that alterations in CORT secretion following photoperiod alteration may be mediated through differences in CRFR1 gene expression or changes in MR:GR mRNA ratios. These findings provide insight into the potential mechanisms by which the HPA axis adapts to photoperiod and diet.

Stress as a potential moderator of ovarian hormone influences on binge eating in women.

Previous research has demonstrated significant associations between increased levels of ovarian hormones and increased rates of binge eating (BE) in women. However, whereas all women experience fluctuations in ovarian hormones across the menstrual cycle, not all women binge eat in response to these fluctuations, suggesting that other factors must contribute. Stress is one potential contributing factor. Specifically, it may be that hormone-BE associations are stronger in women who experience high levels of stress, particularly as stress has been shown to be a precipitant to BE episodes in women. To date, no studies have directly examined stress as a moderator of hormone-BE associations, but indirect data (that is, associations between BE and stress and between ovarian hormones and stress) could provide initial clues about moderating effects. Given the above, the purpose of this narrative review was to evaluate these indirect data and their promise for understanding the role of stress in hormone-BE associations. Studies examining associations between all three phenotypes (that is, ovarian hormones, stress, and BE) in animals and humans were reviewed to provide the most thorough and up-to-date review of the literature on the potential moderating effects of stress on ovarian hormone–BE associations. Overall, current evidence suggests that associations between hormones and BE may be stronger in women with high stress levels, possibly via altered hypothalamic–pituitary–adrenal axis response to stress and increased sensitivity to and altered effects of ovarian hormones during stress. Additional studies are necessary to directly examine stress as a moderator of ovarian hormone–BE associations and identify the mechanisms underlying these effects.

The association between the serum total cortisol as an adrenal response biomarker and severe community-acquired pneumonia

IntroductionThe serum total cortisol is a biomarker to adrenal response in stressful conditions including infection. This study aims to estimate the serum total cortisol level in severe community-acquired pneumonia (CAP) and to study its relation to the severity of illness.Patients and methodsThe study included 50 patients, who with severe CAP were admitted to the ICU of National Institute of Chest Diseases (Embaba), and 20 healthy adults as the control. Ethical approval done by ASU ethical approval team as the paper was taken from masters thesis. The severity of CAP was estimated using pneumonia severity index (PSI) and CURB65 scores. The two groups were subjected to the estimation of serum total cortisol level (8 a.m.) by electrochemiluminescence immunoassay.ResultsSerum total cortisol level significantly increased in the patient group than in the control group (20.356±11.198 and 15.070±1.384 μg/dl, respectively). Serum total cortisol level was positively correlated with PSI but not with CURB65 score.ConclusionSevere CAP is associated with increased serum total cortisol level compared to normal. Serum total cortisol level was positively correlated with the disease severity as estimated by PSI.