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The developmental expression of neurofilament and glial filament proteins in the human pituitary gland: an immunohistochemical study with monoclonal antibodies.

Monoclonal antibodies (MA) specific for neurofilaments (NF) and glial filaments (GF) were used to study the development of the normal human pituitary gland in fetuses, premature infants and adults. A total of 16 serially sectioned pituitary glands was examined. The expression of both NF and GF proteins correlated with maturation of the pituitary gland. Axons, but not cell bodies, were observed to contain immunoreactive NF proteins and these labeled axons were restricted almost exclusively to the pars nervosa. However, in early stages of development, intra-axonal NF proteins were not detectable. Aggregates of NF material in ' blobs ' were also observed in the pars nervosa of adults and a premature infant who survived 6 months following birth. They were never observed in more immature pituitary glands. Cells containing immunoreactive GF proteins were present in all subdivisions of the pituitary gland and they were more common in later stages of development. However, such cells represented only a minority of those present in the pituitary gland and cells in the pars distalis did not express GF protein until after birth. ' Blobs ' comprised of immunoreactive GF proteins were also seen. They were restricted to the pars nervosa and appeared later in development.

Adult↗

Independent differentiation of mammotropes and somatotropes in the chicken embryonic pituitary gland. Analysis by cell distribution and attempt to detect somatomammotropes.

It has been reported that mammotropes in a rodent pituitary gland are derived from somatotropes via somatomammotropes (SMTs), cells that produce both growth hormone (GH) and prolactin (Prl). However, no studies have been done on the transdifferentiation of somatotropes in the chicken pituitary gland. In this study, in order to determine the origin of mammotropes, we studied detail property of appearance of chicken somatotropes, mammotropes and pit-1 cells and then evaluated the existence of SMTs in the chicken embryonic pituitary gland. Immunohistochemical analysis revealed that GH-immunopositive (GH-ip) cells appeared on embryonic day (E) 14 and were mainly distributed in the caudal lobe, while Prl-immunopositive (Prl-ip) cells appeared in the cephalic lobe of the pituitary gland on E16. In situ hybridization (ISH) and RT-PCR analysis showed that expression of GH and Prl mRNA starts at E12 in the caudal lobe and at E14 in the cephalic lobe respectively. Pit-1 mRNA was first detected on E5 by RT-PCR, and pit-1 mRNA-expressing cells were found in the cephalic lobe on E8. Then with the ontogeny of the chicken, these cells spread into both lobes. Using a double staining method with ISH and immunohistochemistry, we could not detect the existence of SMTs in the chicken embryonic pituitary gland even in the marginal region of either lobe. These results suggest that chicken somatotropes and mammotropes independently appear in different lobes of pituitary gland and that transdifferentiation from somatotropes to mammotropes is not the central route for differentiation of mammotropes in the embryonic chicken pituitary gland.

Animals↗

Endoscope-assisted image-guided approach to the pituitary gland: preliminary cadaveric study.

The microscopic transsphenoidal approach to the pituitary gland is the current standard technique used by neurosurgeons to operate the pituitary gland. The endoscopic transsphenoidal approach to the pituitary gland is a current trend because more neurosurgeons are becoming familiar with the use of endoscopes. The use of associated image-guided surgery (or surgical navigation technology; these names are equivalent and are used interchangeably) allows a precise approach that increases the safety and efficacy of a surgical procedure. The InstaTrack system (GE Medical Systems Navigation and Visualization, Inc., Lawrence, MA) is a frameless electromagnetic navigational system used in this study. The objectives of this preliminary and conceptual cadaveric study (three heads) are to get familiarized with the use of image guidance and the study of the endoscopic anatomy of this region and to investigate the technical requirements and benefits of possible future shifting from microscopic towards endoscopic image guidance.

Cadaver↗

Metastatic tumor of the pituitary gland.

Although metastatic tumors of the pituitary gland and the sellar region are not common, they may radiographically mimic a pituitary tumor. Because the metastasis frequently involves the posterior lobe and because lateral extension to the cavernous sinus is common, patients may present with ptosis, diplopia, or diabetes insipidus. Decrease in anterior pituitary function is less common. Metastatic tumors contain abundant vascular networks, as evidenced by frequent blush on cerebral angiography and increased bleeding at operation. We report the case of a 57-year-old woman who presented with rapid onset of bilateral ptosis and ophthalmoplegia and was found to have a metastatic carcinoma within the pituitary gland.

Brain Neoplasms↗

Cell fractionation of anterior pituitary glands from beef and pig.

Fresh anterior pituitary glands from beef and pig were separated by differential centrifugation into subcellular fractions. Nuclei and debris were obtained at 700 g for 15 minutes, secretory granules at 7000 g for 20 minutes, mitochondria at 34,000 g for 15 minutes, and microsomes at 78,000 g for 3 hours. Electron micrographs were taken of the individual fractions. Each fraction was analyzed for nitrogen, pentosenucleic acid (PNA), and phospholipide. Beef and pig anterior lobes were quite similar in their intracellular composition as seen in the subcellular fractions. Succinic dehydrogenase was localized in mitochondria, while alkaline phosphatase was concentrated in the microsomes. A proteinase with pH optimum at 8.2 was exclusively localized. in microsomal and supernatant fractions. Acid phosphatase, acid ribonuclease, and acid proteinase were distributed among the subcellular fractions in another pattern, indicating the presence of a particle type distinct from mitochondria and microsomes. The distribution of cytoplasmic PNA paralleled that of alkaline phosphatase.

Acid Phosphatase↗

Magnetic resonance imaging of the pituitary gland in patients with secondary hypogonadism due to transfusional hemochromatosis.

To identify pituitary iron overload in patients with transfusional hemochromatosis causing secondary hypogonadism, we prospectively evaluated signal intensity abnormalities of the anterior lobe of the pituitary gland of 18 patients affected by transfusion-dependent thalassemia major and secondary hypogonadism. Magnetic resonance (MR) imaging is useful to assess pituitary iron overload in patients with transfusional hemochromatosis and secondary hypogonadism by detection of a significant decreased signal intensity of the anterior lobe of the pituitary gland on GRE T2*-weighted images. The decreased signal intensity of the anterior lobe of the pituitary gland on GRE T2*-weighted images was correlated to increasing serum ferritin level (r = -0.84, r2 = -0.70, P < 0.001). Indeed, the lower the signal intensity of the pituitary gland, the greater the serum ferritin level. However an exact quantification of pituitary iron overload by correlation with serum ferritin level is not allowed. No correlation was found between MR imaging results and hormonal status; however, the detection of pituitary iron overload on GRE T2*-weighted images is consistent with the hypothesis of hypogonadotrophic pituitary insufficiency due to iron-induced cellular damage.

Adolescent↗

Malignant tumors in the pituitary gland.

Malignant tumors of the pituitary gland may mimic pituitary adenomas both in clinical presentation and in imaging, and often present with neurologic findings including visual field loss and extraocular movement palsies. We describe a 58-year-old woman without known malignancy who presented with extraocular movement weakness, loss of facial sensation, and a sellar plasmacytoma; a 49-year-old woman with oculomotor palsy, no known malignancy, and rapidly failing vision who had metastatic lung carcinoma; and a 70-year-old woman with metastatic breast carcinoma who presented with rapidly failing vision and a metastasis to the anterior lobe of the pituitary. These cases illustrate several important features of malignancy in the pituitary fossa: that it can mimic a "nonfunctioning" pituitary adenoma in clinical presentation and imaging; that rapidly progressive visual loss, extraocular movement palsies, or facial sensory loss may help to distinguish it from a benign adenoma; and that when the pathologist evaluates an alleged "nonsecretory" or "nonfunctional" adenoma, metastases should be included in the differential diagnosis.

Adenocarcinoma↗

Induced expression of c-fos in the diencephalon and pituitary gland of goats following transportation.

To identify regions of the caprine diencephalone and pituitary gland related to transportation stress, the expression of c-fos protein was examined immunohistochemically as an indicator of neural activation. Ten castrated Shiba goats (Capra hircus), five transported and five controls, were used. Transported goats were trucked for 1 h and killed by transcardiac perfusion 1 h after the end of transportation. Control goats were housed in single pens killed in the same manner and at the same time as the transported goats. The diencephalon and the pituitary gland were removed after perfusion and used for immunostaining. Plasma cortisol concentrations during and after transportation also were investigated. During transportation, plasma cortisol concentrations increased (P < 0.05) compared with those in the controls. In the diencephalon, c-fos immunoreactive cells were detected in the subcallosa, the lateral septal area, the bed nucleus of stria terminalis (BNST), the preoptic hypothalamic area (POA), the suprachiasmatic nucleus (SCN), the supraoptic nucleus, the paraventricular hypothalamic nucleus parvocellular (PVNp), the paraventricular hypothalamic nucleus magnocellular (PVNm), the arcuate nucleus (ARC), the paraventricular thalamic nucleus, and the stria medullaris in both control and transported goats. The numbers of c-fos immunoreactive cells were increased (P < 0.05) by transportation in the PVNm, the PVNp, the BNST, the POA, the ARC, and the SCN (P < 0.10). In the anterior pituitary gland, the number of c-fos immunoreactive cells in transported goats was 4 to 30 times as much as in control goats; however, there were no differences in the intermediate and posterior lobes between control and transported goats. This study has identified regions in the caprine diencephalon and pituitary gland that show transport-induced increases in c-fos immunoreactive cells. In conclusion, the PVNm, the PVNp, the BNST, the POA, the SCN in the diencephalons, and the anterior lobe of pituitary gland may be involved in the stress responses of goats to transportation.

Animal Husbandry↗

[Histopathological findings of the pituitary gland in cases of subarachnoid hemorrhage].

Histopathological change of the pituitary gland in cases of the central nervous system disorder, especially in the cases of subarachnoid hemorrhage, was studied. Clinical materials were 23 cases who were died from subarachnoid hemorrhage due to aneurysmal rupture in the acute stage. Histopathological change was examined not only of the pituitary gland but also hypothalamus and the change due to increased intracranial pressure (midbrain hemorrhage and uncal herniation). Main histopathological findings of the pituitary gland are anterior pituitary necrosis and they are found in 8 cases out of 23 subarachnoid hemorrhage cases (34.9%). Histopathological changes in hypothalamus were hemorrhage or infarction, and these changes were present in 16 cases (70%). Eight cases with pituitary necrosis had shown hypothalamic lesions. Three cases out of 23 cases (17.4%) showed midbrain hemorrhage and uncal herniation and 3 cases out of these 4 cases had anterior pituitary necrosis. According to the angiographic findings, vasospasm tended to be severe and widespread in cases of anterior pituitary necrosis, meanwhile vasospasm did not tend to be severe or widespread in cases without anterior pituitary necrosis. It was suspected that the mechanism of the development of pituitary necrosis is related not only to the circulatory disturbance of the portal vessels due to mechanical compression on the pituitary stalk and acutely raised intracranial pressure at the moment of aneurysmal rupture, but also circulatory disturbance of the portal vessels due to vasospasm.

Adult↗

Angiopoietins are expressed in the normal rat pituitary gland.

Interaction of vascular endothelial growth factor (VEGF) with the angiopoietins (Ang) is an essential component of angiogenesis. Localization of VEGF in the anterior pituitary raises the possibility that Ang must be present in the pituitary gland as well. In this study Ang expression was detected in the normal rat pituitary gland at the gene level by reverse-transcriptase polymerase chain reaction and at the protein level by immunohistochemistry. The latter was analyzed by both light and confocal microscopy. Constitutive expression of Ang1, Ang2, and their receptor Tie2 was detected at both the mRNA and protein level in all the pituitary glands studied. Of interest was the localization of both Ang1 and Ang2 in scattered PAS positive adenohypophysial cells rather than in endothelial cells. Confocal microscopy showed colocalization of both Ang1 and Ang2 proteins within the same adenohypophysial cells. Dual immunostaining for Ang1 and the anterior pituitary hormones that show PAS positivity demonstrated colocalization of Ang1 with follicle stimulating hormone and luteinizing hormone. In the posterior pituitary, strong Ang1 signal observed in vascular endothelial cells masked the weak Ang2 signal, a pattern that is similar to that reported in brain endothelial cells. The presence of both angiopoietins and VEGF in the pituitary gland suggest that these ligands interact during angiogenesis as they are known to do in other systems to maintain the rich vascular network of the gland. This first report of angiopoietin localization in the rat pituitary gland opens a new line of investigation on angiogenesis in pituitary glands that will impact human endocrinology in the future.

Angiopoietin-1↗

Carbonic anhydrase isoenzyme II is located in corticotrophs of the human pituitary gland.

We studied the location of carbonic anhydrase (CA) isoenzymes I, II, and VI in human pituitary gland using specific antisera in conjunction with immunoblotting, immunoperoxidase, and double immunofluorescence staining techniques. Stainings with anti-CA II serum showed intense cytoplasmic reaction in the anterior lobe of the pituitary gland. Double immunofluorescence staining was used to identify the cells that expressed CA II. Confocal laser scanning microscopy revealed that, of the anterior pituitary hormones studied, ACTH coincides mainly with CA II in these cells. Stainings with anti-CA I and VI sera were negative in the endocrine cells of the pituitary gland. Western blotting of the pituitary gland with anti-CA II revealed a distinct 29-KD polypeptide band corresponding in molecular weight to CA II, suggesting that the antiserum does not detect any nonspecific protein. Anti-CA I serum similarly showed a major 29-KD band, possibly recognizing the enzyme, which is abundantly present in erythrocytes. The results indicate that CA II is expressed in corticotrophs of human pituitary gland, in which its physiological role may be linked to the regulation of optimal pH in the secretory vesicles for the cleavage of ACTH from its precursor.

Adult↗

Presence by radioimmunoassay of a calcitonin-like substance in porcine pituitary glands.

We studied acidic acetone extracts of whole porcine pituitary glands for the presence of immunoreactive calcitonin (CT) using a porcine CT (pCT) RIA which did not react with other known pituitary hormones. Four preparations of porcine pituitary extract contained immunoreactive CT. Three of these displayed inhibition of binding parallel to that of authentic pCT in the pCT RIA and contained a single peak of immunoreactivity similar to pCT when studied by two different gel filtration chromatography systems. One preparation of porcine pituitary extract showed nonparallelism in RIA dose-dilution experiments and multiple immunoreactive species both similar to and larger than pCT on gel filtration in 6 M guanidine HCl. The effect of the reduction of disulfide bonds, followed by carboxymethylation of sulfhydryl groups, on immunoreactivity and apparent molecular size was similar for the CT-like substance in porcine pituitary extract and for authentic pCT. Preliminary immunohistological studies showed cytoplasmic staining in cells of the porcine adenohypophysis. These results demonstrate that the porcine pituitary gland contains a substance which has some of the immunochemical and biochemical properties of thyroidal pCT.

Animals↗

Pituitary gland metastases.

BACKGROUND: Symptomatic pituitary metastasis is an uncommon clinical problem. It may be difficult to distinguish pituitary metastasis from pituitary adenomas both clinically and radiographically. We present our experience with these tumors and compare it with the findings in the literature. METHODS: Eight cases are reported here. The medical records were reviewed concerning clinical features, radiographic findings, treatment, and outcome. RESULTS: Diabetes insipidus is associated with each case and was the initial manifestation of systemic malignancy in two of our patients. Half of the patients had headaches as well. Panhypopituitarism and visual field defects were noted in 25% of the patients. In 50% of the patients metastasis was limited to the pituitary gland only. All patients received radiation treatment and exogenous vasopressin. Two patients underwent resection of the tumor. Five patients died within a few months of diagnosis of pituitary metastasis. One patient died 2 years after the diagnosis and two patients were lost to follow-up. CONCLUSIONS: When a patient with known metastatic cancer develops diabetes insipidus and has radiographic evidence of a pituitary mass, the diagnosis of metastasis is highly probable. Reasonable treatment is palliative with exogenous vasopressin and radiotherapy.

Adult↗

Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas.

PURPOSE: To compare the MR appearance of the pituitary glands of healthy volunteers with that of patients with microadenomas. METHODS: Unenhanced coronal T1-weighted MR of the pituitary gland was performed on 52 healthy adult volunteers and 14 consecutive patients with evidence of pituitary adenomas. The MRs were interpreted in a randomized, blinded fashion. Notation was made of pituitary gland size, symmetry, stalk position, and the gland's signal uniformity. RESULTS: Focal pituitary gland hypointensities were seen in 20 of 52 volunteers and in all 14 patients. In the volunteers, on average the areas of low signal were smaller and not as dark as in the patient group, but there was some overlap between the two groups. Pituitary gland size, symmetry, and stalk position did not differ between the two groups. CONCLUSIONS: Focal hypointensities are common incidental MR findings in the healthy population. On average they appear smaller and not as dark as microadenomas.

Adenoma↗

Characterization of neurophysin in the anterior pituitary gland of sheep.

Portions of sheep anterior pituitary lobe tissue were extracted under acid conditions and assayed for the two neurophysins (oN-III and oN-I/II) by radioimmunoassay. In all tissues examined, oN-III and oN-I/II immunoreactivities were detected. Using a combination of isoelectric focusing and polyacrylamide gel electrophoresis, the neurophysins of the anterior pituitary gland behaved like oN-III and oN-I/II. oN-III of the anterior pituitary was purified by affinity chromatography and high-performance liquid chromatography. This corticotroph oN possessed an amino acid analysis similar to that of oN-III and an N-terminal amino acid sequence, including residues 1-24, identical to that of authentic oN-III. These findings support the work of others who have identified neurohypophysial hormones in the anterior pituitary gland.

Amino Acid Sequence↗