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The Journal of Clinical Investigation Jul 1992Recent experimental data have revealed that activins and inhibins exert pivotal effects on development. As part of our studies on growth and differentiation of the human...
Recent experimental data have revealed that activins and inhibins exert pivotal effects on development. As part of our studies on growth and differentiation of the human fetal adrenal gland, we examined the subunit localization, as well as the mitogenic and steroidogenic actions of activin and inhibin in human fetal and adult adrenals. All three activin and inhibin subunit proteins (alpha, beta A, and beta B) were detected in the fetal and adult adrenal cortex. Immunoreactive activin-A dimer was demonstrated in midgestation fetal and neonatal adrenals. ACTH1-24-stimulated fetal adrenal cell expression of alpha and beta A subunit messenger RNA. In addition, ACTH elicited a rise in levels of immunoreactive alpha subunit secreted by fetal and adult adrenal cells. Human recombinant activin-A inhibited mitogenesis and enhanced ACTH-stimulated cortisol secretion by cultured fetal zone cells, but not definitive zone or adult adrenal cells. Recombinant inhibin-A had no apparent mitogenic or steroidogenic effects. Thus, activin selectively suppressed fetal zone proliferation and enhanced the ACTH-induced shift in the cortisol/dehydroepiandrosterone sulfate ratio of fetal zone steroid production. These data indicate that activin-A may be an autocrine or paracrine factor regulated by ACTH, involved in modulating growth and differentiated function of the human fetal adrenal gland.
Topics: Activins; Adrenal Glands; Adrenocorticotropic Hormone; Cell Differentiation; Fetus; Humans; Hydrocortisone; Immunohistochemistry; Inhibins; RNA, Messenger
PubMed: 1321838
DOI: 10.1172/JCI115827 -
Diagnostic Pathology Aug 2014Spironolactone is often used to treat hypertension caused by hyperaldosteronism, and as a result, can form concentrically laminated electron dense spironolactone body...
BACKGROUND
Spironolactone is often used to treat hypertension caused by hyperaldosteronism, and as a result, can form concentrically laminated electron dense spironolactone body inclusions within the adrenal gland. Spironolactone bodies have not been investigated in a contemporary cohort or in patients treated with the more recently approved aldosterone antagonist, eplerenone.
METHODS
Spironolactone bodies were retrospectively investigated in patients treated for hyperaldosteronism (n=15) from 2012-2013 that underwent a subsequent adrenalectomy.
RESULTS
Inclusions were identified in 33% of patients treated with aldosterone antagonists, far less than previously reported. Remarkably, 50% of patients treated with spironolactone had inclusions while no patients using eplerenone alone had inclusions. Two patients treated with spironolactone had bodies present longer than the duration described in prior studies. Inclusions unexpectedly persisted in 1 patient despite increased duration of discontinued pharmacological treatment. A spectrum of histologic and ultrastructural findings were encountered within an adrenal cortical adenoma from a patient treated with both spironolactone and eplerenone. Ultrastructural examination revealed laminated electron dense bodies with the appearance of classic spironolactone inclusions as well as electron dense bodies without laminations and laminated bodies without electron dense cores.
CONCLUSIONS
Our incidence rate of spironolactone bodies was much lower than previously reported, with no inclusions seen in patients treated solely with the newer aldosterone antagonist, eplerenone. Pathologists should be aware of these infrequently encountered inclusions, particularly as the clinical history of hyperaldosteronism and pharmacologic treatment may not be provided.
VIRTUAL SLIDES
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4597918761268031.
Topics: Adrenal Glands; Adrenalectomy; Adult; Aged; Eplerenone; Female; Humans; Hyperaldosteronism; Hypertension; Incidence; Inclusion Bodies; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Retrospective Studies; Spironolactone
PubMed: 25108298
DOI: 10.1186/1746-1596-9-147 -
The American Journal of Pathology Jul 1985For determination of the kinetics of uptake and subcellular localization of lipopolysaccharide (LPS) from LPS-high density lipoprotein (LPS-HDL) complexes in the adrenal...
For determination of the kinetics of uptake and subcellular localization of lipopolysaccharide (LPS) from LPS-high density lipoprotein (LPS-HDL) complexes in the adrenal gland, LPS-HDL complexes were isolated by immunoaffinity chromatography of 125I-Salmonella minnesota Re595 LPS that had been incubated with 20 mM EDTA-rabbit plasma. After intravenous injection of LPS-HDL complexes in rabbits, preferential uptake of the LPS was observed in the adrenal, so that by 5 hours, adrenal-tissue-bound LPS concentrations (determined by use of 131I-BSA blood marker) exceeded all other tissues examined, including liver and spleen, by at least three-fold. For determination of the subcellular localization of LPS, cholesterol-rich (lipid droplet) fractions and cholesterol-depleted fractions were obtained by ultracentrifugation of homogenates of adrenal tissue from rabbits killed at various times after injection of LPS-HDL complexes. As much as 40% of the adrenal-tissue-bound LPS was recovered in the cholesterol-rich fraction 2.5-24 hours after injection of LPS-HDL complexes. Electron-microscopic autoradiographic and immunocytochemical analysis of adrenal cortex of animals killed 5 hours after injection of LPS-HDL complexes demonstrated specific localization of LPS in lipid droplets. These data thus provide direct evidence for the uptake of LPS into the adrenal cortex of animals with intravascular LPS-HDL complexes and indicate that further study of the effect of LPS on adrenocortical function is warranted.
Topics: Adrenal Cortex; Adrenal Glands; Animals; Autoradiography; Cholesterol; Histocytochemistry; Immunochemistry; Kinetics; Lipopolysaccharides; Lipoproteins, HDL; Rabbits; Salmonella; Subcellular Fractions; Tissue Distribution
PubMed: 4014444
DOI: No ID Found -
Scientific Reports Sep 2018Bilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and bear a lifetime risk of adrenal crisis. Adrenal autotransplantation is...
Bilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and bear a lifetime risk of adrenal crisis. Adrenal autotransplantation is considered useful to avoid adrenal crisis and glucocorticoid replacement therapy. However, the basic process of regeneration in adrenal autografts is poorly understood. Here, we investigated the essential regeneration factors in rat adrenocortical autografts, with a focus on the factors involved in adrenal development and steroidogenesis, such as Hh signalling. A remarkable renewal in cell proliferation and increase in Cyp11b1, which encodes 11-beta-hydroxylase, occurred in adrenocortical autografts from 2-3 weeks after autotransplantation. Serum corticosterone and adrenocorticotropic hormone levels were almost recovered to sham level at 4 weeks after autotransplantation. The adrenocortical autografts showed increased Dhh expression at 3 weeks after autotransplantation, but not Shh, which is the only Hh family member to have been reported to be expressed in the adrenal gland. Increased Gli1 expression was also found in the regenerated capsule at 3 weeks after autotransplantation. Dhh and Gli1 might function in concert to regenerate adrenocortical autografts. This is the first report to clearly show Dhh expression and its elevation in the adrenal gland.
Topics: Adrenal Glands; Animals; Autografts; Cell Proliferation; Hedgehog Proteins; Male; Rats; Rats, Wistar; Regeneration; Signal Transduction; Zinc Finger Protein GLI1
PubMed: 30266964
DOI: 10.1038/s41598-018-32870-9 -
Modulation of autotransplanted adrenal gland by endothelin-1: a morphological and biochemical study.The Anatomical Record Sep 1996Adrenal gland autotransplantation, a model of cortical tissue regeneration, provides the reconstruction of distinct functional and morphological zonae. A morphological...
BACKGROUND
Adrenal gland autotransplantation, a model of cortical tissue regeneration, provides the reconstruction of distinct functional and morphological zonae. A morphological and biochemical study of the adrenal gland of adult male rats after autotransplantation and endothelin-1 (ET-1) administration was made.
METHODS
The technique involved bilateral adrenalectomy and placement of pieces of the adrenal gland in a dorsal plane between the skin and muscle. The animals were killed 90 days after the autotransplantation and 1 hr after intravenous ET-1 administration (0.5 microgram/kg body weight). The autotransplanted pieces were removed, fixed, and processed for light and electron microscopic morphologic studies. Trunk blood was collected for steroid assay.
RESULTS
Saline-treated control autotransplanted animals showed no remarkable differences in adrenal organization; grafts exhibiting a mass of regenerated cortical tissue were arranged in nests of glandular cells surrounded by a fibrous capsule and intersected by layers of connective tissue. The adrenal medulla was systematically absent. Ultrastructure of ET-1-treated animals revealed an inner area in the graft, consisting mainly of fasciculatalike cells. Cytoplasmic changes were evident, with high variations in mitochondrial size and arrangement. Profiles of smooth endoplasmic reticulum sometimes exhibited evidence of hypertrophy. Glandular cells in the graft outer area (subcapsular) were almost invariably like glomerulosa; however, some of them showed mitochondria with a peculiar arrangement of the cristae. "Hybrid" cells with mitochondria resembling those of the zona reticularis were also observed in the subcapsular environment. ET-1-stimulated animals showed significant increases in plasma corticosterone and aldosterone concentrations.
CONCLUSIONS
Endothelin-1, previously reported to stimulate acutely the aldosterone secretion by the adrenal zona glomerulosa in the rat, seems to exert a modulator role on the physiology of adrenal autotransplants, their regeneration and secretion.
Topics: Adrenal Glands; Animals; Endothelin-1; Hormones; Injections, Intravenous; Male; Microscopy, Electron; Osmolar Concentration; Rats; Rats, Wistar; Transplantation, Autologous; Transplantation, Heterotopic
PubMed: 8876828
DOI: 10.1002/(SICI)1097-0185(199609)246:1<98::AID-AR11>3.0.CO;2-# -
Development (Cambridge, England) Dec 2012Adrenal and gonadal steroids are essential for life and reproduction. The orphan nuclear receptor SF1 (NR5A1) has been shown to regulate the expression of enzymes...
Adrenal and gonadal steroids are essential for life and reproduction. The orphan nuclear receptor SF1 (NR5A1) has been shown to regulate the expression of enzymes involved in steroid production in vitro. However, the in vivo role of this transcription factor in steroidogenesis has not been elucidated. In this study, we have generated steroidogenic-specific Cre-expressing mice to lineage mark and delete Sf1 in differentiated steroid-producing cells of the testis, the ovary and the adrenal gland. Our data show that SF1 is a regulator of the expression of steroidogenic genes in all three organs. In addition, Sf1 deletion leads to a radical change in cell morphology and loss of identity. Surprisingly, sexual development and reproduction in mutant animals were not compromised owing, in part, to the presence of a small proportion of SF1-positive cells. In contrast to the testis and ovary, the mutant adult adrenal gland showed a lack of Sf1-deleted cells and our studies suggest that steroidogenic adrenal cells during foetal stages require Sf1 to give rise to the adult adrenal population. This study is the first to show the in vivo requirements of SF1 in steroidogenesis and provides novel data on the cellular consequences of the loss of this protein specifically within steroid-producing cells.
Topics: Adrenal Glands; Animals; Bacterial Proteins; Cholesterol Side-Chain Cleavage Enzyme; DNA-Binding Proteins; Embryo, Mammalian; Female; Gene Deletion; Gonadal Steroid Hormones; Integrases; Luminescent Proteins; Male; Mice; Mice, Transgenic; Ovary; RNA Splicing Factors; Testis; Transcription Factors; Transgenes
PubMed: 23136395
DOI: 10.1242/dev.087247 -
International Journal of Molecular... May 2024Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their... (Review)
Review
Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.
Topics: Humans; Connexins; Gap Junctions; Adrenal Gland Neoplasms; Carcinogenesis; Adrenal Glands; Animals; Gene Expression Regulation, Neoplastic
PubMed: 38791437
DOI: 10.3390/ijms25105399 -
Lakartidningen Apr 2023Adrenohepatic fusion (AHF) is a union of the right adrenal gland and the liver with intermingling of parenchymal adrenal and liver cells. The phenomenon can be of... (Review)
Review
Adrenohepatic fusion (AHF) is a union of the right adrenal gland and the liver with intermingling of parenchymal adrenal and liver cells. The phenomenon can be of clinical importance when evaluating patients with adrenal tumors. Using conventional imaging techniques such as computed tomography, a benign adrenal adenoma developing in an adrenohepatic fusion may mimic an invasive hepatocellular carcinoma or adrenal cortical carcinoma. This study presents a comprehensive review of the literature and shows a prevalence of 5.6 percent in autopsy studies. Moreover, 19 patients with adrenal masses in AHF are presented together with their clinical data.
Topics: Humans; Adrenal Cortex Neoplasms; Liver Neoplasms; Clinical Relevance; Adrenocortical Adenoma; Adrenal Glands; Adrenal Gland Neoplasms
PubMed: 37052304
DOI: No ID Found -
Endokrynologia Polska 2015Over the last 18 months we operated on six patients with large adrenal gland cysts in our centre. This consisted of 8.2% of all patients treated in said period due to... (Review)
Review
MATERIAL AND METHODS
Over the last 18 months we operated on six patients with large adrenal gland cysts in our centre. This consisted of 8.2% of all patients treated in said period due to adrenal gland pathologies. On ruling out malignancy or parasitic nature of the lesions, all patients were surgically treated in order to excise the cysts while leaving the gland untouched. In five patients the cysts were resected but the adrenal gland was spared. However, in one patient the adrenal gland coated the entire cystic mass, which imposed performance of adrenalectomy in addition to cystectomy. During surgeries we tried not to clip the suprarenal vein, which we managed to do in four out of six cases.
RESULTS
A one-year remote follow-up period revealed no cyst recurrence in ultrasound or CT, and it was possible to visualise the remaining part of the adrenal gland in all cases.
CONCLUSION
Thus, in our opinion resection of benign cysts is well justified and recommendable.
Topics: Adrenal Glands; Adult; Cysts; Female; Humans; Laparoscopy; Male; Middle Aged; Treatment Outcome
PubMed: 26457502
DOI: 10.5603/EP.2015.0057 -
BMC Veterinary Research Aug 2016The anatomy of the adrenal glands has been widely studied in many species of domestic and wild mammals. However, there are no available literature reports describing the...
BACKGROUND
The anatomy of the adrenal glands has been widely studied in many species of domestic and wild mammals. However, there are no available literature reports describing the morphology and morphometry of the adrenal glands of the European bison (Bison bonasus).
RESULTS
The study was conducted on 97 European bison of both sexes. The growth of the adrenal glands corresponded to the growth of the whole body, with the largest increase in size occurring in the first 2 years of the animal's life, followed by a slower increase in size until the animal was 5-7 years old. There were no statistically significant differences between ipsilateral adrenal glands of males and females with respect to age. There was no statistically significant difference in weight between the left and the right adrenal gland. However, there was a difference in the length, width and thickness of the two glands. Reference intervals for adrenal gland size and weight were computed separately for two bison age groups (up to 2 years of age and older than two years). The adrenal gland consisted of a cortex and a medulla. The connective-tissue capsule contained two layers. It had a fibrous structure and abundant adipose tissue. The cortex was divided into three zones. The zona glomerulosa contained cells arranged in bundles and curves. Numerous apoptotic cells were observed among regular cells in the zona reticularis. There were vacuoles in the cells of both zona fasciculata and zona reticularis, which formed a foamy cytoplasm. The adrenal medulla was composed of large, dark cells with a highly basophilic cytoplasm in the superficial region and of smaller, lighter cells in deeper layers. Sinusoidal vessels were located in the central part of the medulla.
CONCLUSIONS
The left adrenal gland was significantly longer, narrower and thinner than the right one. There were no significant differences in the structure of the adrenal medulla and cortex of the European bison compared to other species of domestic and wild mammals. There was a thick layer of adipose cells at numerous locations in the adrenal capsule of the bison.
Topics: Adipose Tissue; Adrenal Glands; Animals; Bison; Female; Male
PubMed: 27487830
DOI: 10.1186/s12917-016-0783-8