Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules

Dopamine (DA) regulates both prolactin (PRL) secretion and gene expression, whereas somatostatin (SRIF) inhibits GH secretion with unclear effects on GH gene expression. We therefore tested the effects of SRIF analogs and chimeric SRIF/DA compounds BIM 23A760 and BIM 23A761 on GH and PRL secretion and gene expression in primary rat pituitary cultures and pituitary tumor GH(3) and MMQ cells. Chimeric SRIF/DA molecules suppressed GH release with a similar efficacy to SRIF receptor subtype 2 agonists in rat pituitary and GH(3) cells. After 24 h, BIM 23A760 and BIM 23A761 did not exert additive effects on GH secretion, and after 48 h were less effective than the combination of respective mono-receptor agonists in GH(3) cells. Real-time PCR did not reveal changes in GH mRNA levels after treatment with SRIF analogs and SRIF/DA molecules. SRIF/DA compounds suppressed PRL and PRL mRNA in rat pituitary and MMQ cells with a similar efficacy to D(2)-DA receptor agonist. In GH(3) cells, they suppressed PRL and PRL mRNA levels with a similar efficacy to SRIF receptor subtype 2 agonists. SRIF/DA molecules did not exhibit additive effects on PRL secretion and mRNA levels as compared with cotreatment with mono-receptor ligands. The results show that SRIF analogs and SRIF/DA molecules inhibit GH and PRL secretion and suppress PRL but not GH gene expression.     

A comparison between previous and present histologic assessments of chronic hepatitis C viral infections in humans

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Molecular characterization of a novel form of (A gamma delta beta)zero thalassemia deletion in a Chinese family

We have identified and molecularly characterized a novel deletion in the beta-globin gene cluster that is associated with elevated fetal hemoglobin in the adult. The propositus is a homozygote from the Yunnan province of China. The deletion spans about 90 kb of DNA and removes the A gamma, delta, and beta-globin genes. The 5' breakpoint of the deletion is located about 0.13 kb upstream from the A gamma-globin gene, whereas the 3' breakpoint is located about 66 kb downstream from the beta-globin gene, about 13 kb upstream from the breakpoint of the Chinese (A gamma delta beta)zero-thalassemia. Heterozygotes for this Yunnanese form of (A gamma delta beta)zero-thalassemia express between 9% and 17% of fetal hemoglobin, whereas the homozygote present with a mild anemia (Hb = 10.7 g/dl). Comparison of the sites of 3' breakpoints of the Yunnanese and the Chinese (A gamma delta beta)zero-thalassemia mutants is compatible with the hypothesis that an enhancer element is located between the 3' breakpoints of these two mutants. Juxta-position to the G gamma gene of this element may be responsible for the efficient gamma-gene expression in the Yunnanese mutant.     

Identification and characterization of a high-affinity granulocyte- macrophage colony-stimulating factor receptor on primary rat oligodendrocytes

We previously showed the presence of receptors for granulocyte- macrophage colony-stimulating factor (GM-CSF) on tumor tissues and tumor cell lines that are derived from the neural crest. To determine whether normal neural cells express functional GM-CSF receptors, we isolated and analyzed primary rat brain cells, including microglia, astrocytes, and oligodendrocytes. Scatchard analysis of equilibrium binding of 125I-GM-CSF to primary rat oligodendrocytes showed an average of 1,110 GM-CSF binding sites per cell, with a kd of 20 pmol/L. In six separate experiments, no specific binding was detectable on the astrocyte population. Microglia were used in competitive binding experiments with oligodendrocytes, and addition of microglia did not increase the specific binding of labeled ligand to oligodendrocytes. In dose-response assays, we measured 3H-thymidine uptake in rat oligodendrocytes, microglia and control murine 32D cells stimulated with various concentrations of GM-CSF. Over concentration ranges of 0.025 to 1000 pmol/L, cell proliferation and peak 3H-thymidine incorporation was observed at approximately 30 pmol/L for both the control cells and the oligodendrocytes. However, the microglial cells did not proliferate in response to GM-CSF. These data indicate the presence of a functional receptor for GM-CSF on primary rat oligodendrocytes, and suggest that hematopoietic growth factors such as GM-CSF may play a role in nerve cell development, function, or response to injury.