natriuretic-peptide--c-type and Adenoma

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within -214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas.

Topics: Adenoma; Adult; Aged; Animals; Cells, Cultured; Female; Fetus; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Natriuretic Peptide, C-Type; Pituitary Gland; Pituitary Neoplasms; Pregnancy; Rats; Receptors, Atrial Natriuretic Factor

C-type natriuretic peptide (CNP) in human adrenal glands and adrenal tumors was measured with a specific radioimmunoassay for CNP. Tissue immunoreactive (IR-) CNP concentrations were 0.54 +/- 0.40 pmol/g wet tissue (gwt) (mean +/- SD) in 14 pheochromocytomas, 0.69 +/- 0.19 pmol/gwt in six adrenocortical tumors, and 0.49 +/- 0.22 pmol/gwt in seven normal adrenal glands (cortex and medulla mixed). These concentrations were comparable to those found in tissues from human brains. Sephadex G-50 superfine column chromatography and reverse-phase high performance liquid chromatography revealed that IR-CNP in normal adrenal glands and pheochromocytoma consisted of at least two components: a component in low molecular weight form chromatographically identical to CNP-22 and the other, a high molecular weight form very similar to human CNP-53. This study has shown that IR-CNP is present in human adrenal glands and adrenal tumors with similar molecular forms and comparable concentrations to those in the human brain.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Pheochromocytoma; Radioimmunoassay