Noradrenergic and peptidergic innervation of the mouse femur bone marrow.

The innervation of bone marrow from femur bones of BALB/c mice was studied by means of immunohistochemistry and fluorescence histochemistry. The immunoperoxidase method with nickel amplification was applied to visualize the topographical distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), catecholamine synthesizing enzyme tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Glyoxylic acid-induced fluorescence was also applied to demonstrate catecholamine-containing nerves. Both staining methods revealed dense innervation by fibers seen predominantly around blood vessels but also ramifying among marrow cells. Recent findings on adrenergic and peptidergic influences on marrow physiology combined with anatomical data indicate the existence of a neural modulation of hematopoiesis.

Modulation of the respiratory burst in human neutrophils by isoproterenol and dibutyryl cyclic AMP.

The effects of a beta-adrenergic agonist and a cyclic AMP analogue on activation, activity, and termination of FMLP-stimulated superoxide anion production were investigated. Incubation with isoproterenol resulted in a 50% reduction in the maximal rate of superoxide production and a 3-4-fold increase in the rate of termination of superoxide production. Exposure to 1 mM dibutyryl cyclic AMP resulted in a 40% decrease in the maximal rate and a 3-fold increase in the rate of termination of FMLP-induced superoxide production. Neither agent had a significant effect on the lag time prior to superoxide anion generation.

Continuous and pulsatile infusions of luteinizing hormone have identical effects on steroidogenic capacity and sensitivity of Leydig cells in rats passively immunized against gonadotropin-releasing hormone.

Adult male rats were passively immunized against GnRH and given iv infusions of saline or 60 or 300 ng NIDDK ovine LH-24/100 g BW.24 h in continuous regimens of 2.5 or 12.5 ng/100 g BW.h and pulsatile regimens of 1-min pulses of 5 or 25 ng/100 g BW every 2 h. Control animals were treated with nonimmune serum and saline. After 10 days of in vivo treatment, Leydig cells were purified and incubated in vitro with 1) increasing concentrations of hCG (0-50 mIU/ml) in the presence or absence of methylisobutylxanthine, 2) a maximally stimulatory concentration of 8-bromo-cAMP (8-Br-cAMP; 1 mM), and 3) a saturating concentration of 25-hydroxycholesterol (10 microM). LH receptor concentrations were quantified by [125I]hCG binding assay. Maximum testosterone production in the presence of hCG, 8-Br-cAMP, or 25-hydroxycholesterol was reduced by more than 90% in Leydig cells from anti-GnRH serum-treated rats (compared to that in cells from control rats), and this reduction in steroidogenic capacity was prevented in a dose-dependent manner by concurrent infusion of LH in either the continuous or pulsatile regimens. These results confirm that the trophic actions of LH on Leydig cells in vivo 1) do not depend on pulsatile secretion of the hormone, and 2) include induction/maintenance of one or more of the enzymes catalyzing the conversion of cholesterol to testosterone. Trophic actions on constituents or processes before cholesterol side-chain cleavage were not apparent; in vivo treatments had no obvious differential effects on hCG-stimulated, 8-Br-cAMP-stimulated, or 25-hydroxycholesterol-supported testosterone production. Sensitivity to hCG was increased (EC50 for stimulation of testosterone production was decreased) by passive immunization against GnRH, and this effect was prevented in a dose-dependent manner by concurrent infusion of LH in either the continuous or pulsatile regimens. Thus, intermittent exposure to low concentrations of LH in vivo desensitizes Leydig cells as effectively as continuous exposure. Neither specific binding of [125I]hCG nor the effect of methylisobutylxanthine on sensitivity to hCG in vitro differed among treatment groups. Therefore, both the trophic and desensitizing actions of LH appear to occur by mechanisms that are independent of changes in available LH receptor concentration and phosphodiesterase activity.