Enlightening the adrenal gland

The secretion of glucocorticoid hormones is tightly regulated by the circadian clock and by negative humoral feedback loops, both acting on the hypothalamic-pituitary gland-adrenal axis. However, a new study Ishida et al., 2005 [this issue of Cell Metabolism) shows that light can influence the adrenal's glucocorticoid output by a more direct pathway.     

Dynorphin and enkephalins in adrenal paraneurones. Opiates in the adrenal medulla

Immunoreactive dynorphin (ir-Dyn), immunoreactive leucine-enkephalin (ir-Leu-Enk) and various other neuropeptides were measured in acid extracts of bovine adrenal medulla and isolated adrenal chromaffin cells. Their respective levels ranged as follows: Leu-Enk greater than Dyn greater than bombesin greater than vasoactive intestinal peptide (VIP) greater than neurotensin greater than substance P. Comparisons of the total catecholamine levels with the levels of Leu-Enk in both extracts gave ratios in the same order of magnitude (2600, tissue extract and 5000, cell extract). However, the catecholamine/Dyn ratio in the tissue extract (138 000) was much higher than that found in the cell extract (20 180), suggesting a possible selective degradation of Dyn in tissue extract as compared with cell extract or an induction of Dyn biosynthesis in cells which have been isolated from their natural microenvironment. Immunofluorescence staining of isolated chromaffin cell sections revealed the presence of ir-Dyn in 5 to 10% of the total cell population. To localize ir-Dyn in regard to Leu-Enk and catecholamines, adrenal chromaffin cells were separated into three populations (I, II, and III) on a stepwise bovine serum albumin (BSA) gradient. Relative high levels of ir-Dyn were measured in cell layer I (4 pmol/10(6) cells), a cell population enriched in noradrenaline. However, ir-Leu-Enk was more concentrated in cell layers II and III (5.3 and 8.3 pmol/10(6) cells), two populations enriched in adrenaline. Isolation and high pressure liquid chromatography (HPLC) analysis of adrenomedullary Dyn indicated the presence of at least five molecular forms corresponding to Dyn-(1-11), Dyn-(1-12), Dyn-(1-13), Ala-containing-Dyn-(1-13) and a nonidentified molecule eluting closely to Dyn-(1-13). These data indicate that adrenal ir-Dyn and ir-Leu-Enk have distinct cellular distributions. In addition, the identification of Dyn fragments in bovine adrenal medulla indicates that these short peptides may be considered as natural active forms of Dyn.     

Operations on the adrenal glands

Various conditions of the adrenal gland are amenable to surgical treatment. Removal of a pheochromocytoma is almost always indicated when the tumor is diagnosed. The results of extirpation have been excellent in cases in which patients were operated upon before the onset of chronic hypertension. Removal of the "nerve cell" tumors of the adrenal is indicated if metastasis cannot be demonstrated. Hypofunction of the adrenal cortex may be partially alleviated by the repeated implantation of pellets of desoxycorticosterone acetate. Hyperfunction of the adrenal cortex causes a variety of clinical manifestations depending upon which of the numerous hormones are affected. Removal of a cortical tumor alleviates these symptoms. These tumors are malignant in more than 50 per cent of cases, and recurrence is frequent. Bilateral hyperplasia of the glands rather than a tumor may be present. In such circumstances, resection of 95 per cent of the adrenal tissue is effective in controlling the symptoms of the disease. Total bilateral excision of the adrenals is, at present, under investigation as a means of treatment for a variety of conditions.     

Hypertrophy of the adrenal cortex

The human adrenal cortex in essential hypertension and in the salt-losing form of the adrenogenital syndrome and the adrenal cortex in spontaneously hypertensive rats were studied by morphometry. Under long-term functional loading hypertrophy of adrenocortical cells is the common way of increasing the mass of the cortex. The correlation between the morphological parameters of the adrenocortical structures increases in this condition. Hyperplasia along with hypertrophy has been found in man at an early age. The differences in the degree of hypertrophy of the nuclei and nucleoli may be connected with different intensity of adrenocortical function in different pathological conditions.     

Immunohistochemical localization of adrenal ferredoxin and distribution of adrenal ferredoxin and cytochrome P-450 in the rat adrenal

Adrenal ferredoxin, the iron-sulfur protein associated with cytochromes P-450 in adrenocortical mitochondria, has been localized immunohistochemically at the light microscopic level in rat adrenals by employing rabbit antiserum to bovine adrenal ferredoxin in both an unlabeled antibody peroxidase-antiperoxidase method and an indirect fluorescent antibody method. When sections of rat adrenals were exposed to the adrenal ferredoxin antiserum in both procedures, positive staining for adrenal ferredoxin was observed in parenchymal cells of the three cortical zones but not in medullary chromaffin cells. Marked differences in the intensity of staining, however, where observed among the three cortical zones: the most intense staining being found in the zona fasciculata, less in the zona reticularis, and least in the zona glomerulosa. Furthermore, differences in staining intensity were also observed among cells within both the zona fasciculata and the zona reticularis. In agreement with these immunohistochemical observations, determinations of adrenal ferredoxin contents by electron paramagnetic resonance (EPR) spectrometry in homogenates prepared from capsular and decapsulated rat adrenals revealed that the concentration of adrenal ferredoxin in the zona glomerulosa was lower than that in the zona fasciculata-reticularis. Similar results were obtained when the contents of cytochrome P-450 were determined in capsular adn decapsulated rat adrenal homogenates. These observations indicate that adrenal ferrodoxin and cytochrome P-450 are not distributed uniformly throughout the rat adrenal cortex.     

The adrenal

During the past 15 years, considerable progress has been made in our understanding of the genetic basis of adrenal development and function. More than 30 single gene disorders have now been identified that can affect the hypothalamic-pituitary-adrenal axis in humans (fig. 1, 2; table 1). This review highlights recent advances in the molecular pathology of: (1) adrenal hypoplasia, (2) adrenal destruction, (3) disorders of adrenal steroidogenesis, (4) adrenal steroid resistance and (5) activation of the adrenal axis/tumorigenesis. Characterizing the molecular basis and natural history of these conditions is providing fascinating insight into adrenal development and function and can help to focus treatment and counselling of patients appropriately. However, ongoing translation of research findings into clinical practice is needed if patient care is to be influenced significantly.