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  • 1
    Electronic Resource
    Electronic Resource
    Expression of von Hippel-Lindau Protein (VHL-P) in Nontumorous and Adenomatous Human Pituitaries (1999)
    Springer
    Pituitary 1 (1999), S. 227-232 
    Details
    ISSN: 1573-7403
    Keywords: angiogenesis ; immunocytochemistry ; pituitary ; VHL protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the presence of von Hippel-Lindau protein (VHL-P) in 7 nontumorous pituitaries and 68 pituitary adenomas by immunocytochemistry using a polyclonal antibody which detects both normal and mutated forms. In nontumorous pituitary VHL-P was variable expressed in the cytoplasm of most adenohypophysial cells. In addition, weak diffuse staining was noted in the posterior lobe. Among the 53 VHL-P immunopositive adenomas (78%), 32 showed only cytoplasmic, 7 only nuclear, and 14 both cytoplasmic and nuclear immunoreactivity. In densely (8 cases) and sparsely (7 cases) granulated somatotroph adenomas nuclear and weak cytoplasmic immunoreactivity were common; all 4 sparsely granulated lactotroph adenomas had only moderate cytoplasmic immunostaining; all 7 functioning corticotroph adenomas presented intense cytoplasmic immunoreactivity and 4/7 showing nuclear immunostaining as well; all 3 silent subtype 1 adenomas were negative; 3/4 silent subtype 2 and 4/7 silent subtype 3 adenomas exhibited only cytoplasmic immunoreactivity; thyrotroph adenomas showed variable patterns from negative in 1/7, to only cytoplasmic in 2/7, nuclear alone in 2/7, or both in 2/7. Only weak, focal cytoplasmic immunoreactivity was noted in gonadotroph adenomas of female (2/4) and male 1/5 type. Lastly, all 4 null cell and 8 oncocytic adenomas showed moderate to intense cytoplasmic immunoreactivity. It can be concluded that the majority of pituitary adenomas express the VHL-P with variable distributions and intensity in different tumor types. The frequent localization of VHL-P in the nuclei of somatotroph adenomas, the least vascularized tumor type, suggests a possible inhibitory role of VHL-P in pituitary angiogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009990005835
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Distribution and Regulation of Proconvertases PC1 and PC2 in Human Pituitary Adenomas (1999)
    Springer
    Pituitary 1 (1999), S. 187-195 
    Details
    ISSN: 1573-7403
    Keywords: pituitary ; proconvertase ; chromogranin ; pancreastatin ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pituitary adenomas are members of the family of neuroendocrine cells and tumors which have secretory granules containing chromogranins/secretogranins and other proteins. Pituitary adenomas express the neuroendocrine specific proconvertases PC1 (also known as PC3) and PC2, which are important for the proteolytic processing of chromogranins/secretogranins molecules. We examined the distribution of PC1 and PC2 in primary cultures of 20 pituitary adenomas and analyzed the regulation of the proconvertase mRNAs and proteins by various secretagogues including hypothalamic hormones and phorbol ester to determine the role of PC1 and PC2 in CgA processing in pituitary adenomas. Although PC2 was present in all adenomas, there was a differential distribution of PC1 with PRL adenomas expressing lower levels of PC1 compared to other adenoma types by RT-PCR analysis, in situ hybridization and immunostaining. Treatment of primary cultures of pituitary adenomas with phorbol 12-myristrate 13-acetate (PMA) resulted in an increase in pancreastatin (PST) secretion in most pituitary adenomas and increased PC1 mRNA and protein expression in gonadotroph adenomas, but not in other types of adenomas. Analysis of a human pituitary adenoma cell line, immortalized by recombinant defective adenovirus (HP75), which expressed chromogranin A, FSH, PC1 and PC2 showed that PST was secreted by these immortalized cells. Treatment with TGFβ1 resulted in an increase in PST secretion and in PC1 mRNA and protein. These results indicate that a) there is a differential distribution of PC1 in human pituitary adenomas with PRL adenomas expressing very little PC1 mRNA and protein and b) that PC1 expression in gonadotropin hormone-producing adenomas is regulated by PMA and TGFβ1. These findings support the observation that chromogranin A is a substrate for the endoproteinase PC1 in human pituitary adenoma cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009909232243
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Leptin Signal Transduction in the HP75 Human Pituitary Cell Line (2000)
    Springer
    Pituitary 3 (2000), S. 211-220 
    Details
    ISSN: 1573-7403
    Keywords: pituitary ; HP75 cells ; STATs and SOCS-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leptin is an adipocyte-derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor (OB-R). Activation of the long form of OB-R (OB-Rb) results in JAK2 phosphorylation, activation of STATs, and subsequent gene expression. Activated STAT3 induces SOCS-3 expression in some cell types, which in turn down-regulates the JAK/STAT pathway. Although both leptin and OB-R are expressed in pituitary cells, the mechanism of signal transduction and its regulation in this organ has not been studied extensively. In these experiments we show that leptin reduces proliferation in a human pituitary cell line (HP75) and also increased apoptosis in these cells. Leptin also increased SOCS-3 mRNA and protein expression and tyrosine-phosphorylation in the HP75 human pituitary cell line. These findings suggest that SOCS-3 plays an important role in the inhibition of proximal leptin signal transduction in the anterior pituitary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012994712851
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    Paper (German National Licenses)
    Fulltext
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