6 research outputs found
The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice
Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally
believed to inhibit IGF action in the circulation. In contrast, IGFBP-1
has been reported to interact with cell surfaces and enhance IGF-I action
locally in some tissues. Renal IGFBP-1 levels are found elevated in
various conditions characterized by renal growth (e.g. diabetes mellitus,
hypokalemia). To test whether IGFBP-1 is a renotropic factor, IGFBP-1 was
administered alone or in combination with IGF-I to Snell dwarf mice, an in
vivo model without compensatory feedback effects on growth hormone (GH)
secretion. In three control groups of Snell dwarf mice, placebo, GH or
IGF-I was administered. Compared with placebo, kidney weight increased in
all treated groups, however, with different effects on kidney morphology.
Administration of IGF-I, alone or in combination with IGFBP-1, tended to
increase glomerular volume, while no changes were seen in the other
groups. Administration of IGFBP-1 or IGFBP-1+IGF-I both caused dilatation
of the thin limbs of Henle's loop, while GH or IGF-I administration had no
visible effect. Furthermore, IGF-I administration resulted in an increased
mean number of nuclei per cortical area and renal weight, whereas GH,
IGF-I+IGFBP-1 or IGFBP-1 caused a decreased renal nuclei number. In situ
hybridization and immunohistochemistry showed specific changes of the
renal IGF system expression patterns in the different groups.
Particularly, IGFBP-1 administration resulted in extensive changes in the
mRNA expression of the renal IGF system, whereas the other administration
regimen resulted in less prominent modifications. In contrast,
administration of IGFBP-1 and IGFBP-1+IGF-I resulted in identical changes
in the protein expression of the renal IGF system. Our results indicate
that IGFBP-1, alone or in combination with IGF-I, demonstrated effects on
the renal tubular system that differ from the effects of IGF-I
Growth hormone expression in murine bone marrow cells is independent of the pituitary transcription factor Pit-1
GH has beer shown to promote the development and function of leukocytes. The expression of both GH and GH-receptors in lymphoid cells has led to the hypothesis that GH acts in an autocrine or paracrine fashion. The described effects of GH on hematopoiesis and B cell development, led us to investigate GH expression in bone marrow cells. By immunocytochemistry, we show that bone marrow-derived granulocytes and macrophages contain immunoreactive GH. We found that 65 ± 24% of the granulocytes were stained with anti-GH, whereas 5.8 ± 1.5% of the granulocytes contained detectable amounts of GH mRNA as assessed by in situ hybridization. To address a possible alternative regulation mechanism in bone marrow and to establish whether locally derived GH might still play a role in pituitary-deficient dwarf mice, we also addressed GH expression in bone marrow from hypopituitary Snell dwarf mice. These mice have a mutated gene for the pituitary transcription factor Pit-1 that is deficient in DNA binding. Our finding that GH expression (immunoreactive protein and mRNA) in bone marrow cells from dwarf mice is similar to that in normal mice points to a Pit-1 independent regulation of GH in mouse bone marrow.SCOPUS: ar.jinfo:eu-repo/semantics/publishe