Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland

The melanocortin-2-receptor (MC2R)/MC2R accessory protein (MRAP) complex is critical to the production of glucocorticoids from the adrenal cortex. Inactivating mutations in either MC2R or MRAP result in the clinical condition familial glucocorticoid deficiency. The localisation of MC2R together with MRAP within the adrenal gland has not previously been reported. Furthermore, MRAP2, a paralogue of MRAP, has been shown in vitro to have a similar function to MRAP, facilitating MC2R trafficking and responsiveness to ACTH. Despite similar MC2R accessory functions, in vivo, patients with inactivating mutations of MRAP fail to be rescued by a functioning MRAP2 gene, suggesting differences in adrenal expression, localisation and/or function between the two MRAPs. In this study on the rat adrenal gland, we demonstrate that while MRAP and MC2R are highly expressed in the zona fasciculata, MRAP2 is expressed throughout the adrenal cortex in low quantities. In the developing adrenal gland, both MRAP and MRAP2 are equally well expressed. The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. Interestingly, expression of MC2R and MRAP in the undifferentiated zone would support the notion that ACTH may play an important role in adrenal cell differentiation and maintenance

Corticosteroid-Binding Globulin is expressed in the adrenal gland and its absence impairs corticosterone synthesis and secretion in a sex-dependent manner

Corticosteroid-binding globulin (CBG) is synthesized by the liver and secreted into the bloodstream where binds to glucocorticoids. Thus CBG has the role of glucocorticoid transport and free hormone control. In addition, CBG has been detected in some extrahepatic tissues without a known role. CBG-deficient mice show decreased total corticosterone levels with missing of classical sexual dimorphism, increased free corticosterone, higher adrenal gland size and altered HPA axis response to stress. Our aim was to ascertain whether CBG deficiency could affect the endocrine synthetic activity of adrenal gland and if the adrenal gland produces CBG. We determined the expression in adrenal gland of proteins involved in the cholesterol uptake and its transport to mitochondria and the main enzymes involved in the corticosterone, aldosterone and catecholamine synthesis. The results showed that CBG is synthesized in the adrenal gland. CBG-deficiency reduced the expression of ACTH receptor, SRB1 and the main genes involved in the adrenal hormones synthesis, stronger in females resulting in the loss of sexual dimorphism in corticosteroid adrenal synthesis, despite corticosterone content in adrenal glands from CBG-deficient females was similar to wildtype ones. In conclusion, these results point to an unexplored and relevant role of CBG in the adrenal gland functionality related to corticosterone production and release

Numerical Evaluation of Microwave Thermal Ablation to Treat Small Adrenocortical Masses

In this paper microwave thermal ablation is numerically evaluated in the context of a treatment for Conn’s Syndrome. This condition is caused by a benign shallow tumour in the cortex of adrenal gland. The modelling and design of microwave applicator to deliver thermal ablation to the adrenal gland requires accurate tissue characterisation. Measuring the dielectric properties of the constituent tissues in the adrenal gland, i.e. cortex and medulla, enables more accurate numerical modelling for electromagnetic and thermal simulations. This study presents an anatomically and dielectrically realistic numerical model of the adrenal gland, and investigates the feasibility of applying controlled heating to small targets in the adrenal cortex. In addition, the use of dielectric contrast between the fat and the cortex of the adrenal gland to focus the thermal energy in the gland has also been studied. Being conscious of limitations of numerical simulation of complex multiphysics problems like the microwave ablative treatment, calculated results provide a preliminary description of the electromagnetic and thermal phenomena involved

Sexual Differentiation of Circadian Clock Function in the Adrenal Gland

Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders

The Influence of Exposure to Stress of Pregnant Rats on the Adrenal Gland Structure of their Offspring. An Unbiased Stereological Study

Many factors may interact with normal differentiation and growth of tissues and cells. Stress might be  experienced during pregnancy and it has been shown that stress may cause low birth weight. The effect of  prenatal manipulations on the HPA axis has been focused on physiological and biochemical alteration of  the adrenal gland. A stereological examination of the influences of prenatal stress on the structure of the  developing adrenal gland of one day and 21 day-old rats has now been performed. In this study experiments were conducted to test the hypothesis that exposure to restraint stress during pregnancy  in rat results in structural changes in the developing adrenal gland of their pups. Female rats were exposed to restraint stress from the first day of pregnancy throughout gestation. Male offspring  of stressed rats (PS= experimental) and of unstressed mothers (C= control) who were one day and 21  days of age were selected. Their body weight (BW), crown-rump length (CRL), biparietal diameter (BPD),  volume of the gland and the cortical layers and medulla were estimated using stereological methods. The results showed that the prenatal stress led to a decrease in BW, but CRL and BPD remained unchanged.  Also, a significant increase in volume of the adrenal gland and cortical layers in one day and 21 day-old  offspring were observed. The volume of the medulla of the adrenal gland of neonate rats remained  unchanged but the volume of the medulla in 21 day-old rats was decreased. Therefore, it can be concluded that prenatal stress alters the structure of the developing adrenal gland.

Electric Countershock and Cold Stress Effects on Liver and Adrenal Gland

OBJECTIVES: Cold exposure induces glycogen and lipid depletion in the liver and the adrenal gland, respectively. However, no previous study has determined the effects of electrical countershock on those tissues. We aimed to evaluate the effects of electrical countershock on lipid depletion in the adrenal gland and on glycogen depletion in the liver. METHODS: We used 40 male Wistar rats divided into four groups: the control group, in which the animals were subjected to a resting period of seven days; the electrical discharge group, in which the animals were subjected to a resting period followed by administration of ten 300-mV electrical discharges; the electrical post-discharge group, in which the animals received ten electrical shocks (300 mV) followed by rest for seven consecutive days; and the cold stress group, in which the animals were subjected to a resting period and were then exposed to -8ºC temperatures for four hours. All animals underwent a laparotomy after treatment. The lipid and glycogen depletions are presented using intensity levels (where + = low intensity and ++++ = high intensity, with intermediate levels in between). RESULTS: The rats exposed to the cold stress presented the highest glycogen and lipid depletion in the liver and the adrenal gland, respectively. Furthermore, we noted that the electrical countershock significantly increased lipid depletion in the adrenal gland and glycogen depletion in the liver. One week after the electrical countershock, the liver and adrenal gland profiles were similar to that of the control group. CONCLUSION: Electrical countershock immediately increased the glycogen depletion in the liver and the lipid depletion in the adrenal gland of rats

Regeneration Studies by Transplantation of Adrenal Tissue

The regeneration ability of the adrenal gland has been observed and recorded by several investigators; however, reports of the method of regeneration have been conflicting. This study was conducted to attempt to learn more of the method of adrenal gland regeneration through transplantation studies

Reaction of chickens to graduated length of exposure to stress

The reactions of 60 day old chickens Arbor Acres 60 X Vantress to immobilization stress lasting 1/2, 1, 2, 4 hours and to application of ACTH, manifested by activity changes in the systems hypophysis-adrenal gland and hypophysis-thyroid gland were studied. The highest activity increase in the two neuro-endocrine systems of the chickens was found to occur after 1/2 hour exposure to stress. With prolonged stress the responses weakened and after 4 hours most of the values gradually regressed to their initial level. The responses of both systems were synchronized. Reactions of the chickens differed from those of laboratory rats in which an increased activity of the hypophysis-adrenal gland system coincided with attenuation of the hypophysis-thyroid gland system

Robot-assisted posterior retroperitoneoscopic adrenalectomy: single port access

Laparoscopic adrenalectomy has become a gold standard in adrenal gland surgery. More recently, some minimally invasive trials have been conducted on single access surgery on the adrenal gland. In this study, we introduce our first experiences of robot-assisted posterior retroperitoneoscopic adrenalectomy using single-port access and the da Vinci system

Metastases or benign adrenal lesions in patients with histopathological verification of lung cancer: Can CT texture analysis distinguish?

INTRODUCTION: Distant metastases are found in the many of patients with lung cancer at time of diagnosis. Several diagnostic tools are available to distinguish between metastatic spread and benign lesions in the adrenal gland. However, all require additional diagnostic steps after the initial CT. The purpose of this study was to evaluate if texture analysis of CT-abnormal adrenal glands on the initial CT correctly differentiates between malignant and benign lesions in patients with confirmed lung cancer. MATERIALS AND METHODS: In this retrospective study 160 patients with endoscopic ultrasound-guided biopsy from the left adrenal gland and a contrast-enhanced CT in portal venous phase were assessed with texture analysis. A region of interest encircling the entire adrenal gland was used and from this dataset the slice with the largest cross section of the lesion was analyzed individually. RESULTS: Several texture parameters showed statistically significantly difference between metastatic and benign lesions but with considerable between-groups overlaps in confidence intervals. Sensitivity and specificity were assessed using ROC-curves, and in univariate binary logistic regression the area under the curve ranged from 36 % (Kurtosis 0.5) to 69 % (Entropy 2.5) compared to 73 % in the best fitting model using multivariate binary logistic regression. CONCLUSION: In lung cancer patients with abnormal adrenal gland at imaging, adrenal gland texture analyses appear not to have any role in discriminating benign from malignant lesions