Comparative studies between hormone contents and morphological appearances in human adrenal cortex. - Special reference to non-functioning tumors (adenoma and adenomatous nodule) and functioning adenoma.
“…Further examination is required to confirm whether there is actually any difference among APA, NFA, and preCS, because the number of preCS cases we investigated was very small. On the other hand, the real-time PCR showed that APA and NFA expressed SYP mRNA at the same, albeit very low, level, which is consistent with the fact that both APA and NFA have the potential for cortisol synthesis within the normal range (33).…”
Design and methods: The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. Results: Immunohistochemical analysis showed that 50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria, and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. Conclusions: We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.European Journal of Endocrinology 161 939-945
“…Further examination is required to confirm whether there is actually any difference among APA, NFA, and preCS, because the number of preCS cases we investigated was very small. On the other hand, the real-time PCR showed that APA and NFA expressed SYP mRNA at the same, albeit very low, level, which is consistent with the fact that both APA and NFA have the potential for cortisol synthesis within the normal range (33).…”
Design and methods: The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. Results: Immunohistochemical analysis showed that 50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria, and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. Conclusions: We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.European Journal of Endocrinology 161 939-945
“…In contrast, the expression level of CYP11B1 mRNA, encoding 11β-hydroxylase, the limiting enzyme in cortisol biosynthesis [18,22], in the control APAs was higher than that in our case. Most APAs have the potential for cortisol as well as aldosterone synthesis [23], while the APA in our patient consisted of only ZG-type cells with no potential for cortisol synthesis [11]. Therefore, it is no surprise that typical APAs expressed CYP11B1 mRNA at higher levels than in our case.…”
C a 2+ is a critical signal for adrenal and gonadal steroid synthesis 1 acting within 2 cellular compartments; Ca 2+ is generated in the cytosol 2,3 and transferred to the mitochondria 4-7 where it activates matrix dehydrogenases to generate reducing equivalents (NAD(P)H) that are essential cofactors for steroid hydroxylation. 8 In aldosterone-producing zona glomerulosa (ZG) cells of the adrenal cortex, the dominant pathway for extra-cellular Ca 2+ entry into the cytoplasmic compartment is plasma membrane voltage-gated Ca 2+ channels, 9 whereas the principal pathway for mitochondrial Ca 2+ uptake is via the mitochon-drial uniporter, a Ca 2+-selective channel. 10 Membrane voltage across each of these compartments regulates Ca 2+ transport and thus the rate of steroid production. Because other ion channels resident in each membrane (plasma and mitochondrial) can change membrane voltage, they too are capable of altering Ca 2+ uptake by mitochondria. 11 Accordingly, it is not surprising that genetic variation in genes encoding ion channels and transporters is now considered central to the pathophysiology of 1 common subtype of primary hyperaldosteronism, unilateral aldosterone-producing adenoma. 12 In aldosterone-producing adenoma, aldosterone synthesis is not strictly controlled by the renin-angiotensin II system and thus is characterized by a large increase in the aldosterone/renin ratio. 13 Yet, the cause of other common endocrine hypertensive disorders in which aldosterone production is inappropriate for the level of renin, such as bilateral adrenal hyperplasia and low renin essential hypertension, 14,15 still remains poorly understood. Our laboratory and that of Barhanin et al have generated mouse models of aldosterone overproduction evoked by deletion of leak potassium channels that generate background currents to establish a negative resting cell membrane voltage. 16-20 The combined deletion of TASK-1 and TASK-3 channels (tandem pore domain acid-sensitive K + channels) leads to excessive aldosterone overproduction and low renin in mice. By contrast, deletion of TASK-3 alone evokes mild hyperal-dosteronism and low renin, 19 whereas that of TASK-1 elicits mild hyperaldosteronism without an accompanying suppression of renin. 21 Genetic variations in the human TASK-1 gene (KCNK3) 21-23 are associated with measures of hypertension (rs1275988, rs13394970) and elevated plasma aldosterone (rs2586886), and KCNK3 mRNA is abundantly expressed in mouse and human adrenal cortex. 24 By contrast, the KCNK9 gene product, TASK-3, is principally expressed in the rodent adrenal cortex, 25 although low levels of message are detected in the human adrenal cortex. 26 The function of TASK-3 in adrenal cortical cells remains unknown. We previously reported that global deletion of TASK-3 in mice produces a mild hyperaldosteronism even though the cell Abstract-Ca 2+ drives aldosterone synthesis in the cytosolic and mitochondrial compartments of the adrenal zona glomerulosa cell. Membrane potential across each of these compartments regu...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.