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

Effect of central neurotropic substances on the hypophysisadrenal cortex system during immobilization of animals

The immobilization of guinea pigs for 5, 12, 24 and 48 hours, by securing to a slab, results in a persistent rise of the blood plasma 17-oxycorticosteroid concentration. Repeated administration of phenobarbital (50 mg/kg) and of the sodium salt of gamma-oxybutyric acid (500 mg/kg), as well as the combined administration of central m- and n-cholinolytics with small doses of phenobarbital tends to inhibit activation of the adrenal cortex during 48 hour immobilization of the animals. Repeated administration of aminazine (20 mg/kg) tends to decrease activation of the adrenal cortex. The administration of reserpine (0.1-5 mg/kg) 12-18 hours before immobilization of guinea pigs increases the response of the hypophysis-adrenal cortex system

The human adrenal cortex: growth control and disorders

This review summarizes key knowledge regarding the development, growth, and growth disorders of the adrenal cortex from a molecular perspective. The adrenal gland consists of two distinct regions: the cortex and the medulla. During embryological development and transition to the adult adrenal gland, the adrenal cortex acquires three different structural and functional zones. Significant progress has been made in understanding the signaling and molecules involved during adrenal cortex zonation. Equally significant is the knowledge obtained regarding the action of peptide factors involved in the maintenance of zonation of the adrenal cortex, such as peptides derived from proopiomelanocortin processing, adrenocorticotropin and N-terminal proopiomelanocortin. Findings regarding the development, maintenance and growth of the adrenal cortex and the molecular factors involved has improved the scientific understanding of disorders that affect adrenal cortex growth. Hypoplasia, hyperplasia and adrenocortical tumors, including adult and pediatric adrenocortical adenomas and carcinomas, are described together with findings regarding molecular and pathway alterations. Comprehensive genomic analyses of adrenocortical tumors have shown gene expression profiles associated with malignancy as well as methylation alterations and the involvement of miRNAs. These findings provide a new perspective on the diagnosis, therapeutic possibilities and prognosis of adrenocortical disorders

Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex

Pathology Associated with Hormones of Adrenal Cortex

Adrenal gland is an endocrine organ comprising of an outer cortex and inner medulla. These secrete various hormones that have a vital role in maintaining the normal homeostasis of the body. Lesions of adrenal cortex are quite common to encounter and most of these are related to the hormones secreted by three layers of adrenal cortex: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Also it is very infrequent to encounter metastatic lesions in the adrenal glands too. So it is very important as a part of a clinician as well as a pathologist to know the pattern in which these hormones are secreted along with their physiological roles. Thus this chapter includes the disease that are related to excess as well as deficiencies of the hormones secreted by adrenal cortex. The chapter also includes various genetic syndromes that are associated with the disorders associated with hormones of adrenal cortex. The last part of the chapter includes a brief description of various benign as well as malignant lesions, the pathological as well as the etiological aspects and the hormonal abnormalities associated. This chapter thus mainly focuses on the pathology associated with the adrenal cortex and hormones secreted by the various layers of adrenal cortex

Morphological and functional manifestations of rat adrenal-cortex response to sodium bromide administration under hypodynamic stress

Functional and morphological manifestations of adrenal cortex response to hypodynamia (2-hr immobilization on an operating table) under the influence of bromine preparations were studied. The sodium bromide was administered intraperitoneally in 100, 250, and 500 mg/kg doses once and repeatedly during ten days. The adrenal gland was evaluated functionally by ascorbic acid and cholesterol content and morphologically by coloring it with hematoxylin-eosin and Sudans for lipid revealing at freezing. Results are displayed in two tables and microphotographs. They are summarized as follows: the bromine weakens the functional state of the adrenal cortex in intact rats, causing changes similar to those under stress. During immobilization combined with preliminary bromine administration, a less pronounced stress reaction is noticeable

Immunohistochemical demonstration of LH/CG receptors in non-neoplastic human adrenal cortex and adrenocortical tumors

Introduction. Numerous data indicate that luteinizing hormone and/or chorionic gonadotropin (LH/CG) exert direct actions on the adrenal cortex and are involved in the adrenal pathology. However, the immunohistochemical studies on the expression of LH/CG receptors (LH/CGR) in the human adrenal cortex and in the adrenocortical tumors are scarce. Material and methods. Paraffin sections of samples of 6 human non-neoplastic adrenal cortex and 25 adrenocortical tumors were immunostained with anti-LH/CGR polyclonal antibody. Results. All zones of the human non-neoplastic adrenal cortex present a positive immunoreaction with anti-LH/CGR antibody showing the strongest reaction in cell membranes. The LH/CGR immunostaining in the vast majority of hormonally non-functioning adenomas and in all hormone-secreting adenomas does not differ from the non-neoplastic adrenal cortex. In contrast to non-neoplastic adrenal cortex and benign adenomas, in adrenocortical cancers the immunostaining with anti-LH/CGR antibody behaves differently. The immunopositive material is almost totally filling the cytoplasm of the cells but the immunopositivity of cell membranes is weak or lacking. Conclusions. The data presented in our study show that the expression of LH/CGR in adrenocortical tumors is not ectopic but eutopic. The immunohistochemical examination of LH/CGR may be useful in the differentiation between benign and malignant lesions in the adrenal cortex. Moreover, the loss of membrane localization of LH/CGR in adrenocortical cancer suggests the alteration of receptors’ function.

Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal β2-adrenergic receptor (β2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal β2-AR antibody. The results show that immunoreactivity for β2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for β2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates β2-AR expression in the human cortex and provides suggestions on the possible involvement of β2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death

The Interplay between Estrogen and Fetal Adrenal Cortex

Estrogen is a steroid hormone that regulates embryogenesis, cell proliferation and differentiation, organogenesis, the timing of parturition, and fetal imprinting by carrying chemical messages from glands to cells within tissues or organs in the body. During development, placenta is the primary source of estrogen production but estrogen can only be produced if the fetus or the mother supplies dehydroepiandrosterone (DHEA), the estrogen prohormone. Studies show that the fetal zone of the fetal adrenal cortex supplies 60% of DHEA for placental estrogen production, and that placental estrogen in turn modulates the morphological and functional development of the fetal adrenal cortex. As such, in developed countries where humans are exposed daily to environmental estrogens, there is concern that the development of fetal adrenal cortex, and in turn, placental estrogen production may be disrupted. This paper discusses fetal adrenal gland development, how endogenous estrogen regulates the structure and function of the fetal adrenal cortex, and highlights the potential role that early life exposure to environmental estrogens may have on the development and endocrinology of the fetal adrenal cortex

FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development

Developmental signalling pathways are implicated in the formation and maintenance of the adrenal gland, but their roles are currently not well defined. In recent years it has emerged that Sonic hedgehog (Shh) and Wnt/β catenin signalling are crucial for the growth and development of the adrenal cortex. Here we demonstrate that Fibroblast growth factor receptor (Fgfr) 2 isoforms IIIb and IIIc are expressed mainly in the adrenal subcapsule during embryogenesis and that specific deletion of the Fgfr2 IIIb isoform impairs adrenal development, causing reduced adrenal growth and impaired expression of SF1 and steroidogenic enzymes. The hypoplastic adrenals also have thicker, disorganised capsules which retain Gli1 expression but no longer express Dlk1. Fgfr2 ligands were detected in both the capsule and the cortex, suggesting the importance of signalling between the capsule and the cortex in adrenal development