Biomedical subjects

H Sasano

Publications and source records attributed to H Sasano.

At least 145 records · Page 8Linked to original sources

PubMed1999

Adrenomedullin in monocytes and macrophages: possible involvement of macrophage-derived adrenomedullin in atherogenesis.

Macrophages secrete a variety of growth factors, cytokines and vasoactive peptides, which are related to the progression of atherosclerosis. Adrenomedullin (ADM) is a potent vasodilator peptide and inhibits proliferation and migration of vascular smooth muscle cells. In this study, we investigated the production and secretion of ADM by monocytes and macrophages by Northern blot analysis, RIA and immunocytochemistry. Northern blot analysis showed that ADM mRNA was expressed in human monocytes obtained from peripheral blood and monocyte-derived macrophages. The expression level of ADM mRNA in monocyte-derived macrophages was about five times higher than that in monocytes. Treatment with lipopolysaccharide (100 ng/ml) for 24 h increased ADM mRNA expression levels in both monocytes and monocyte-derived macrophages. The levels of immunoreactive ADM in the media of monocyte-derived macrophages were about three times higher than that of monocytes (0. 718+/-0.046 fmol/24 h/10(5) cells, n=8 compared with 0.259+/-0.018 fmol/24 h/10(5) cells, n=8; mean+/-S.E.M., P<0.01). The secretion was also increased by treatment with lipopolysaccharide. Immunocytochemistry showed positive ADM immunostaining in macrophages in atherosclerotic lesions of human aorta obtained at autopsy. ADM secreted from activated macrophages may play an inhibitory role in atherogenesis.

Adrenomedullin↗

PubMed1998

A new low density lipoprotein receptor related protein, LRP5, is expressed in hepatocytes and adrenal cortex, and recognizes apolipoprotein E.

The isolation and characterization of rabbit and human cDNAs revealed a new low density lipoprotein receptor (LDLR)-related protein (LRP) designated as LRP5. Human LRP5 cDNA encodes a 1, 616-amino acid type I membrane-like protein with three ligand binding repeats in its extracellular region. LDLR-deficient cells transduced by recombinant adenovirus containing human LRP5 exhibited increased binding of apolipoprotein E (apoE)-enriched beta-migrating very low density lipoprotein. Northern blotting and in situ hybridization revealed a high level of LRP5 expression in hepatocytes and the adrenal gland cortex. In LDLR-deficient Watanabe heritable hyperlipidemic rabbits, LRP5 mRNA was increased in the liver and accumulated in cholesterol-laden foam cells of atherosclerotic lesions.

Adrenal Cortex↗

PubMed1998

Apoptosis and cell proliferation in biliary atresia.

Biliary atresia (BA), which is thought to result from progressive destruction of the bile ducts by a necroinflammatory process, is the most common cause of obstructive jaundice in infancy. Abnormalities in the cell turnover of remodelling ductal plates are considered one of the important aetiological factors in this disorder, but little work has been done on this topic. Programmed cell death or apoptosis was therefore examined by TdT-mediated dUTP biotin nick end labelling (TUNEL) and cell proliferation by Ki67 immunostaining in 34 cases of BA. The results were compared with normal control liver (five cases) and congenital dilatation of the bile ducts (CDB, five cases) in order to study the cell turnover or tissue dynamics of BA. The TUNEL labelling index (LI) in bile ducts (48.9 +/- 13.2 per cent) was significantly higher than that of the control normal liver (3.6 +/- 2.8 per cent) and of CDB (2.5 +/- 5.1 per cent). The Ki67 LI in the bile ducts of BA (15.0 +/- 5.57 per cent) was also significantly higher than that of CDB (8.6 +/- 5.4 per cent). No significant differences of the TUNEL and Ki67 LIs in hepatocytes were, however, observed between BA, CDB, and normal liver. The TUNEL LI was significantly higher than the Ki67 LI in the bile ducts of BA. BA is therefore associated with increased and disorganized cell turnover of the bile ducts, which is related to malformation of the ductal plate or abnormal bile duct development.

Apoptosis↗

PubMed1998

Detection of apoptotic cells in cytology specimens: an application of TdT-mediated dUTP-biotin nick end labeling to cell smears.

We applied TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) to cytologic smears in order to detect the cells undergoing apoptosis. These smears were obtained by scraping the cut surface of 9 cases of carcinoma, including renal-cell carcinoma (3 cases), esophageal squamous-cell carcinoma (3 cases), and gastric adenocarcinoma (3 cases), and were fixed and prepared by different methods. The results were also compared with those of tissue sections. TUNEL in smears was generally associated with higher background nuclear stain than in tissue sections. Smears that were fixed in 4% or 8% paraformaldehyde or absolute methanol exhibited results comparable with those of tissue sections, with minimum background in all cases examined. There were no significant differences in TUNEL labeling index among tissue sections and smears fixed in 4% or 8% paraformaldehyde or in absolute methanol. Smears treated in Carnoy's fixative (3:1 methanol:acetic acid) and air-dried smears demonstrated a higher background. TUNEL positivity could not be detected in slides decolorized from May-Grünwald-Giemsa stain. Markedly high background, which may occur as a result of artifactural DNA breaks, was also observed in slides decolorized from Papanicolaou stain, in which TUNEL-positive cells could be evaluated only in 3/8 cases. Application of the TUNEL method to cytology specimens has disadvantages or limitations compared to its application to histological sections, but the method is considered the most suitable one for detecting cells undergoing apoptosis in cytology materials.

Adenocarcinoma↗

PubMed1998

Treatment of severe postmenopausal endometriosis with an aromatase inhibitor.

OBJECTIVE: To treat an unusually aggressive case of recurrent postmenopausal endometriosis. DESIGN: Case report. SETTING: University of Texas Southwestern Medical Center (Dallas, Texas). PATIENT(S): A 57-year-old woman who presented with recurrent severe endometriosis after hysterectomy and bilateral salpingo-oophorectomy. INTERVENTION(S): Oral administration of anastrozole (an aromatase inhibitor) (1 mg/d) and elemental calcium (1.5 g/d) for 9 months. Alendronate (a nonestrogenic inhibitor of bone resorption), 10 mg/d, was added to this regimen. MAIN OUTCOME MEASURE(S): Reduction in size of endometriotic lesion, pain relief, tissue levels of aromatase P450 messenger RNA, bone density. RESULT(S): Circulating levels of estradiol-17beta were reduced to approximately 50% of the baseline value after the onset of treatment with anastrozole. Pain rapidly decreased and completely disappeared after the 2nd month of treatment. The 30 x 30 x 20-mm bright red polypoid vaginal lesion was reduced to a 3-mm gray tissue by the end of 9 months of treatment. Markedly high pretreatment levels of aromatase P450 messenger RNA in the endometriotic tissue became undetectable in a specimen obtained from a repeated biopsy after 6 months of treatment. Bone density of lumbar spine decreased by 6.2% after 9 months of treatment. CONCLUSION(S): This is the first description of the use of an aromatase inhibitor in the treatment of endometriosis. The short-term results were extraordinarily successful in elimination of pain and near-complete eradication of implants associated with severe endometriosis not responsive to other therapy. We conclude that the recently developed potent aromatase inhibitors are candidate drugs in the treatment of endometriosis that is resistant to standard regimens.

Administration, Oral↗

PubMed1998

Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats.

BACKGROUND & AIMS: We recently showed that activation of the hypothalamus-pituitary-adrenal axis may mitigate the progress of acute pancreatitis. To clarify the mechanism, the role of endogenous glucocorticoids in pancreatic acinar cell death was examined. METHODS: The occurrence of apoptosis was studied in adrenalectomized or sham-operated rats with or without cerulein-induced pancreatitis. The effects of RU38486, a glucocorticoid-receptor antagonist, on the survival of cultured acinar cells (AR42J) were also examined. RESULTS: Adrenalectomy caused increases in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) of acinar nuclei depending on the time after adrenalectomy but not of other cell types in the pancreas and in other digestive organs. Electron microscopy showed the characteristic features of apoptosis in the TUNEL-labeled acinar cells. In cerulein pancreatitis of adrenalectomized rats, the TUNEL-labeled acinar nuclei increased remarkably depending on the time after cerulein infusion. Replacement of glucocorticoids blocked the occurrence of apoptosis in these experiments. RU38486 induced dose dependently the apoptosis of AR42J cells. CONCLUSIONS: These results provide evidence that endogenous glucocorticoids are an important factor for acinar cell survival. Endogenous glucocorticoids may protect acinar cells by decreasing their sensitivity to the induction of cell death during acute pancreatitis.

Acute Disease↗

PubMed1998

Involvement of high density lipoprotein as substrate cholesterol for steroidogenesis by bovine adrenal fasciculo-reticularis cells.

Adrenocorticosteroids are known to be synthesized from cholesterol which may arise from de novo synthesis or from the uptake of low-density lipoproteins (LDL) or high-density lipoproteins (HDL). LDL is reported to be a main substrate for corticosteroid synthesis by bovine adrenocortical cells, although the role of HDL, which is well known to be used for steroid biosynthesis in rat adrenals, is still obscure. Therefore, we examined the role of HDL in the regulation of corticosteroidogenesis in bovine adrenals in order to clarify whether or not HDL was selectively utilized for corticosteroid synthesis in vitro. The present data demonstrated that HDL and LDL increased cortisol production in a dose-dependent manner in bovine adrenocortical cells in vitro, and also that HDL cholesterol increased cortisol production significantly higher than LDL cholesterol did. Addition of adrenocorticotrophic hormone (ACTH) with HDL to the incubation media enhanced much higher cortisol production than that with LDL in short time incubation. The present data also demonstrated that uptake of 125I-HDL was significantly greater than that of 125I-LDL. Thus, HDL rather than LDL is thought to be the preferred lipoprotein as a source of steroidogenic substrate cholesterol in bovine adrenal fasciculo-reticularis cells.

Animals↗

PubMed1998

Adrenocortical tumor in a patient with familial adenomatous polyposis: a case associated with a complete inactivating mutation of the APC gene and unusual histological features.

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disorder caused by a germline inactivating mutation of the adenomatous polyposis coli (APC) gene. Patients with FAP sometimes develop various extracolonic manifestations including adrenocortical neoplasms. We present a 14-year-old boy with FAP who had an adrenocortical tumor with atypical histopathologic features, ie, sex-cord-like differentiation. Immunohistochemical studies of adrenal 4 binding protein (Ad4BP) and steroidogenic enzymes showed the capacity of these tumor cells to produce steroids. Genetic analysis of the tumor disclosed a two-hit mutation in APC: a germline 5-base pair deletion accompanied by a loss of the normal allele. Because there were no reports of genetic alterations in adrenocortical tumors developed in FAP patients, we examined 10 sporadic adrenal tumors (four carcinomas and six adenomas) for mutations in APC. However, no mutations were found in these 10 sporadic adrenal tumors. These results suggest that mutation of APC is also responsible for some fraction of the adrenocortical tumors: the tumor in this case is included.

Adenoma↗

PubMed1998

Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain.

Regional distribution of urocortin-like immunoreactivity (UCN-LI) in the human brain was studied by radioimmunoassay and was compared with that of corticotropin-releasing hormone (CRH). In addition, the expression of UCN mRNA was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) method. UCN-LI was detected in every region of brain examined, including hypothalamus, pons, cerebral cortex, and cerebellum. The concentrations of UCN-LI in the human brain were approximately 3 pmol/g wet weight in any brain region, and no marked regional difference was noted. On the other hand, the highest concentrations of CRH-LI were found in the frontal cortex, temporal cortex, and hypothalamus and the lowest in the pons. Reverse phase high-performance liquid chromatography of the UCN-LI in the human brain extract showed two immunoreactive peaks; one peak eluting earlier and one in the position of synthetic human UCN. RT-PCR showed that UCN mRNA was expressed in every region of brain examined. These findings indicated that UCN and UCN mRNA were widely expressed in the human brain.

Adult↗

PubMed1998

Immunolocalization of aromatase in human breast disorders using different antibodies.

Immunolocalization of aromatase can provide important information about the status of intratumoral aromatase of human breast. We have performed immunohistochemistry of aromatase in surgical pathology specimens of human breast disorders using monoclonal and polyclonal antibodies. Both antibodies yielded satisfactory results in immunostaining of aromatase in normal placenta and normal cycling human ovaries. In human breast disorders, immunostaining or aromatase using monoclonal antibodies can only demonstrate immunoreactivity following antigen retrieval. Immunoreactivity can be detected in both carcinoma and stromal cells but nuclear immunoreactivity, which may be represent artefactural changes, can be detected in both normal and neoplastic breasts. Immunostaining using polyclonal antibody revealed aromatase immunoreactivity in cytoplasm of adipocytes, fibroblasts, vascular wall cells and Schwann cells but intense immunoreactivity was detected in adipocytes adjacent to carcinoma invasion in 68/82 carcinoma cases and stromal cells around carcinoma nest in 58/82 cases. Strong aromatase immunoreactivity was detected in 7/69 benign proliferative breast disorder, 5 of which were sclerosing adenosis. Aromatase immunoreactivity was also detected in carcinoma cells in 7/82 cases but aromatase positive carcinoma cells represent less than 5% of tumor cells in all these cases. These results above indicate that polyclonal antibody is considered to be more suitable for aromatase immunohistochemistry in archival materials of breast disorders but further investigations including easy and reproducible scoring system and production of reliable monoclonal antibodies are required to establish aromatase immunohistochemistry as a reliable method of assessing intratumoral aromatase in human breast disorders.

Antibodies, Monoclonal↗

PubMed1998

Comparison of biochemical aromatase activity with aromatase immunohistochemistry in human breast carcinomas.

The role of intratumoural aromatase in human breast cancer growth remains controversial. At the same time as the use of aromatase inhibitors in the clinical setting continues to increase, so does the need for a tool to predict the likely response to this treatment. Intratumoural aromatase is a candidate predictive marker. The presently accepted 'gold standard' methods of assessment of aromatase activity are biochemical assays. However, these are time-consuming and require relatively large amounts of fresh or frozen tissue which are frequently not available. The development of a reliable immunohistochemical technique for the assessment of intratumoural aromatase which could be applied rapidly to more readily available paraffin-embedded material is therefore highly desirable. Unfortunately aromatase immunohistochemistry is also an area of controversy; some authors describe localisation to the stromal compartment but others to the malignant epithelial cells themselves. The aim of this study was therefore to compare immunohistochemical scores using two different antibodies with biochemical aromatase activity. Taking a group of 29 human breast carcinomas we demonstrated a strong correlation between immunoreactivity with a monoclonal antibody (p = 0.01) but not with a polyclonal (p = 0.16). The monoclonal produced reactivity in both epithelial and stromal cells but the polyclonal in only stromal cells. The implications of these results are discussed together with the need for further studies.

Adult↗

PubMed1998

Aromatase in the human central nervous system.

OBJECTIVE: Oestrogen produced locally by aromatase is thought to participate in numerous biological functions in the adult central nervous system (CNS). However, little is known about aromatase expression in the human CNS. DESIGN: We examined aromatase expression in human brain regions, (4 men, 2 women) obtained from autopsy, by reverse transcriptase (RT)-polymerase chain reaction (PCR) and also studied alternative use of multiple exons 1 of its gene, which is involved in tissue specific expression of aromatase in human. RESULTS: The amount of aromatase mRNA determine by RT-PCR assay in 6 cases tended to be highest in pons, thalamus, hypothalamus and hippocampus. Analysis of multiple exons 1 revealed that 1f, considered specific for brain, as well as 1b (fibrolast type) and 1d (gonadal type), were expressed. 1d and 1f tended to be utilized in hypothalamus, thalamus and amygdala. The amount of overall mRNA expression was also higher in hypothalamus, thalamus and amygdala than in other regions of the brain. There were no differences of utilization of exons 1 and mRNA expression of aromatase between female and male brain. CONCLUSIONS: These results demonstrate that aromatase is expressed widely in various regions of human brain tissues in both men and women.

Adult↗

PubMed1998

Cyclic changes of vasculature and vascular phenotypes in normal human ovaries.

In order to study alterations of angiogenesis and blood vessel regression through ovarian cycle in human ovaries we quantitatively examined vascularity in various stages in 24 normal human ovaries. Vascular density (VD; vessel numbers/10(-7) m2) and endothelial area of each vessel (EA; 10(-12) m2/vessel) were evaluated using immunohistochemistry of CD34 and CAS 200 image analysis system. Small-sized vessels were sporadically observed in stroma adjacent to primordial or primary follicles (6.73 +/- 1.83 for VD and 113.58 +/- 21.80 for EA). Formation of capillary network was observed in the theca layer of preantral follicles (PA; 15.28 +/- 2.77 for VD and 113.58 +/- 21.80 for EA), and higher density of the capillary network was detected in non-dominant follicles in follicular phase (ND-F) and dominant follicles (DF; 29.33 +/- 3.84 for VD and 179.69 +/- 41.25 for EA). Dense capillary network was still present in non-dominant follicles in luteal phase (ND-L) and atretic follicles (AF; 26.88 +/- 3.36 for VD and 110.88 +/- 50.53 for EA). After ovulation, developing capillaries were also observed in the luteinized granulosa layers in early corpus luteum (21.95 +/- 2.06 for VD and 167.08 +/- 29.59 for EA). Vessel density markedly increased in mid corpus luteum, reached plateau in late corpus luteum (60.85 +/- 5.92 for VD and 70.99 +/- 15.57 for EA) and remained constant during degenerating corpora lutea. Vascular endothelial growth factor was immunohistochemically observed in the theca cells in PA, ND-F, DF and ND-L in follicular stages, and functioning corpora lutea. Immunoreactivity of intercellular adhesion molecule-1 was detected only in post-capillary venules in early degenerating corpora lutea. These findings suggest that ovarian angiogenesis is a requirement for the early stages of folliculogenesis and luteal growth, and also plays an important role in the process of follicular atresia and luteal regression.

Actins↗

PubMed1998

Leukocytes in normal-cycling human ovaries: immunohistochemical distribution and characterization.

We investigated, using an image analysis system, the immunohistochemical localization of leukocyte subpopulations and human leukocyte antigen (HLA)-DR in 30 normal-cycling human ovaries in order to better understand local immunological events in human ovaries. All subtypes of T lymphocytes examined (CD3+, CD4+ and CD8+ cells) were sporadically observed in the stroma and theca layers of follicles throughout the menstrual cycle (ranging from 4.32 to 6.25 cells/10(-7) m2, 1.67 to 3.33 cells/10(-7) m2 and 2.33 to 3.44 cells/10(-7) m2, respectively for the three subtypes), and subsequently, increased in number in atretic follicles (78.70 +/- 6.90, 31.13 +/- 2.54 and 43.31 +/- 3.35). After ovulation, the number of T lymphocytes was markedly low in the early and mid corpus luteum (13.88 +/- 1.62, 4.18 +/- 0.50 and 6.53 +/- 0.45). The number increased in the late corpus luteum, and was highest in the late degenerating corpus luteum (255.67 +/- 27.10, 102.12 +/- 7.80 and 137.34 +/- 12.50). HLA-DR was sporadically positive in fibroblasts in the stroma and theca layers of follicles (means ranged from 1.25 to 1.82 cells/10(-7) m2), and increased in atretic follicles (24.68 +/- 2.25). HLA-DR+ cells were markedly low in the early and mid corpus luteum (2.16 +/- 0.88), increased in the late corpus luteum, and reached a plateau in the late degenerating corpus luteum (121.84 +/- 17.73). The great majority of these increased HLA-DR+ cells were macrophages. Results of our study suggest that T lymphocytes and/or macrophages play important roles in luteal regression and follicular atresia in normal-cycling human ovaries.

Adult↗

PubMed1998

A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes.

We report here the identification, characterization, and expression of a novel rat acyl-CoA synthetase (ACS) designated as ACS5. ACS5 consists of 683 amino acids and is approximately 60% identical to the previously characterized ACS1 and ACS2. ACS5 was overproduced in Escherichia coli cells and then purified to near homogeneity. The purified enzyme utilized a wide range of saturated fatty acids similar to those utilized by ACS1 and ACS2, but differed in its preference for C16-C18 unsaturated fatty acids. Northern blot analysis revealed that ACS5 mRNA is present most abundantly in the small intestine, and to a much lesser extent in the lung, liver, adrenal gland, adipose tissue, and kidney. In situ hybridization of rat ileum revealed abundant accumulation of ACS5 transcripts in foveolar epithelial cells. The hepatic level of ACS5 mRNA was significantly increased by refeeding a fat-free high sucrose diet and reduced by fasting or refeeding a high cholesterol diet, whereas that in the small intestine was not significantly altered by various dietary conditions. In contrast to the absence of ACS1 mRNA in undifferentiated 3T3-L1 preadipocytes, ACS5 mRNA was present in proliferating 3T3-L1 preadipocytes and its level remained unaltered during differentiation, suggesting that ACS5 may provide the acyl-CoA utilized for the synthesis of cellular lipids in proliferating preadipocytes.

Adipocytes↗

PubMed1998

Serous borderline ovarian tumor with functioning stroma in a postmenopausal woman: immunohistochemical analysis of steroidogenic pathway.

An epithelial ovarian tumor with estrogenic manifestations (vaginal bleeding, vaginal softening) was encountered in a 70-year-old woman. The preoperative serum levels of estrone, estradiol, and testosterone were elevated. A right ovarian serous papillary tumor of borderline malignancy was removed and found to have a cellular, focally luteinized stroma. Steroidogenic enzymes, including 3beta-hydroxysteroid dehydrogenase and P450 cytochromes specific for cholesterol side-chain cleavage (P450scc), 17alpha-hydroxylation (P45017alpha), and aromatization (P450arom), were immunohistochemically demonstrated in the stromal cells. Immunohistochemical evaluation of these enzymes suggest significant functional differences among the enzymatically-activated stromal cells. That only rare stromal cells were immunoreactive for P450arom suggests that most of the testosterone synthesized in the tumor is extragonadally converted to estrogen, resulting in tumor-associated estrinism.

3-Hydroxysteroid Dehydrogenases↗

PubMed1998

Histopathologic and immunohistochemical study of steroidogenic cells in the stroma of ovarian tumors.

The presence of steroidogenic or enzymatically active stromal cells in ovarian tumors can lead to various endocrine manifestations by the overproduction of sex steroids. We studied the clinicopathologic and immunohistochemical features of histologically identified steroid-type cells or enzymatically active cells in the stroma of ovarian lesions. Among 1,249 ovarian tumors or tumorlike lesions, steroid cells were histologically identified in the stroma in 32 ovarian neoplasms, of which 29 were mucinous cystadenomas. The cells were Leydig- or hilus-type cells in 4 of the tumors and were lutein-type cells in the remaining 28. None of the 32 tumors were immuno-reactive for human chorionic gonadotropin or luteinizing hormone. Lutein-like steroid cells were intermingled with spindle-shaped stromal cells and capillaries, while Leydig-type cells were more often associated with dilated vessels. The transcription factor of steroidogenesis, adrenal 4-binding protein (Ad4BP), was present in nearly all steroid-type stromal cells. However, steroidogenic enzymes, 17 alpha-hydroxylase (C17) and 3 beta-hydroxysteroid dehydrogenase (3 beta SD), were expressed only in 10 of 15 cases of histologically identified steroid cells. Steroid cells in which Ad4BP but not C17 or 3 beta HSD were expressed were all lutein-type. Aromatase was rarely detected in lutein-and Leydig-type cells. The presence of morphologically identified steroid cells does not necessarily indicate expression within these cells of steroidogenic enzymes, a finding that merits further attention.

Adult↗

PubMed1998

A composite silent corticotroph pituitary adenoma with interspersed adrenocortical cells: case report.

OBJECTIVE AND IMPORTANCE: A case report of an extraordinary sellar pituitary tumor composed of corticotrophs and adrenocortical cells is presented. To our knowledge, this is only the second one reported in the literature. CLINICAL PRESENTATION: An 18-year-old female patient presented with amenorrhea. INTERVENTION: Investigations revealed a sellar mass, which was excised transsphenoidally. Histologically, two cell types could be readily distinguished, i.e., small basophilic cells that were positive for periodic acid Schiff and adrenocorticotropic hormone and large cells with abundant, slightly vacuolated, eosinophilic cytoplasm that were negative for periodic acid Schiff and adrenocorticotropic hormone. The nature of the tumor was revealed by ultrastructural examination, thus highlighting the importance of this technique in the investigation of pituitary adenomas. Immunohistochemistry with a panel of steroidogenic dehydrogenases and hydroxylases was positive in the large cells, confirming these as adrenocortical cells. CONCLUSION: We suggest that the designation "composite silent corticotroph pituitary adenoma with adrenocortical cells" is an appropriate name for this tumor. The explanation for the presence of the two cell types is obscure. Two theories are considered, as were proposed by the authors of the previous case report regarding the same entity, i.e., 1) the possibility of misplaced embryonic adrenocortical cells and 2) the presence of uncommitted stem cells that differentiate into adrenocortical cells.

Adenoma↗