Effect of Growth Hormone-Releasing Hormone on Human Peripheral Blood Leukocyte Chemotaxis and Migration in Normal Subjects

Żelazowski, Piotr; Döhler, K.-D.; Stępień, H; Pawlikowski, Marek

doi:10.1159/000125228

Cited by 21 publications

(4 citation statements)

References 17 publications

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“…The normal response in the migrating capacity of PMN in other non GH-PRLsecreting pituitary tumors suggests that the alteration is selective for acromegaly and hyperprolactinemia. Our results are in agreement with previous reports showing that in vitro GH and GH-releasing hormone (GHRH) or PRL decrease the chemotactic response of PMN (17,25,26).…”

Section: Discussionsupporting

confidence: 93%

Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia

Mf²,

Ra³

et al. 1994

European Journal of Endocrinology

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Both growth hormone (GH) and prolactin (PRL) modulate immune responses in vitro. We studied chemotaxis under agarose of polymorphonuclear cells from patients with acromegaly or hyperprolactinemia. Polymorphonuclear cells were purified by dextran sedimentation and subjected to stimulation with N-formylmethionyl-phenylalanine. The results showed a decrease in both directed migration (acromegaly: 971 +/- 155 microns; hyperprolactinemia: 1123 +/- 137 microns, expressed as mean +/- SEM) and spontaneous migration (acromegaly: 270 +/- 77 microns; hyperprolactinemia: 298 +/- 77 microns) when compared to similar features from normal controls (directed migration: 2019 +/- 99 microns; spontaneous migration: 590 +/- 49 microns) and from patients with non-GH/PRL-secreting pituitary tumours (directed migration: 1633 +/- 282 microns; spontaneous migration: 562 +/- 116 microns), suggesting that this defect is selective for acromegaly and hyperprolactinemia. Our results point to a putative direct or indirect effect of GH and PRL on polymorphonuclear cell chemotaxis.

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Section: Discussionsupporting

confidence: 93%

Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia

Mf²,

Ra³

et al. 1994

European Journal of Endocrinology

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“…Two GHRH transcripts, one similar to the 0.75-kb hypothalamic species and a larger transcript of approximately 10 kb, were identified in human lymphocytes (10). The physiological function of immune-derived GHRH is unknown, although supraphysiological concentrations significantly inhibited the chemotactic response of human peripheral lymphocytes (11) and natural killer cell activity in vitro (12). GHRH(-1-29), but not GHRH-(1-44) at low concentrations stimulated, whereas high concentrations inhibited phytohemagglutinin (PHA)-induced lymphoproliferation, interleukin-2 secretion, and interleukin-2 receptor expression on activated human peripheral lymphocytes (13).…”

mentioning

confidence: 99%

The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1

Khorram

Garthwaite

2001

The Journal of Clinical Endocrinology &Amp; Metabolism

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GHRH is a neuropeptide that has also been localized to the immune system. The physiological function of GHRH in the immune system has not been elucidated. This study was conducted to determine whether immune GHRH expression is altered in certain pathological states, such as immune cell tumors, and whether gender, aging, and alterations in the sex steroid milieu influence the expression of this peptide in immune cells. Using double color flow cytometry, GHRH protein was found to be expressed in less than 2% of peripheral blood mononuclear cells (PBMC). Monocytes and B and T cells all expressed GHRH protein, although a greater percentage of T cells compared with B cells and monocytes expressed GHRH (5- to 7-fold). Semiquantitative RT-PCR was used to quantify GHRH messenger ribonucleic acid (mRNA) in PBMC and several immune cell-derived tumors. PBMC and granulocytes expressed low levels of GHRH mRNA with relatively higher levels of expression in monocytes. The tumor cell lines CEMX 174 (B/T cells), HUT 78 (T cells), WIL2-N (B cells), U937 (monocytes/macrophages), and JM 1 (pre-B cell lymphoma) all showed greater expression of GHRH mRNA relative to PBMC. However, two cell lines, CCRF-SB, a B lymphoblastoid cell line, and HL-60, a promyelocytic cell line, expressed GHRH mRNA at similar levels as PBMC. A significant decrease in the percentage of lymphocytes (CD45(+) cells) expressing GHRH protein was found in age-advanced men and women compared with young men and women. This decline was noted in B cells (CD20(+)) and monocytes (CD14(+)), but not in T cells (CD3(+)). GHRH mRNA expression in PBMC derived from postmenopausal women was lower than that from premenopausal women. However, no differences in PBMC GHRH mRNA expression were found in young and old men. Although in older men there were fewer peripheral lymphocytes that express GHRH protein, these cells secreted significantly more GHRH in vitro than cells from postmenopausal women with no hormone replacement therapy (HRT), but similar levels as cells from women receiving HRT. PBMC from women receiving HRT secreted more GHRH in vitro than cells from women receiving no hormone replacement. This study demonstrates that the expression of immune GHRH is dynamic, and therefore likely to be regulated. Increased expression of GHRH in certain immune tumors suggests that GHRH may be mitogenic under certain conditions and therefore play a role in the pathogenesis of select immune cell tumors. Collectively, these results suggest a role for GHRH as a local immune modulator and in the pathophysiology of immunosenescence and immune cell tumors.

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“…Northern blot analysis detected two GHRH mRNA transcripts in lymphocytes, one similar in size to the hypothalamic species of 0.75 Kb and a larger transcript of approximately 10 Kb (20). Though the action of lymphocyte-derived GHRH is currently unknown, supraphysiologic concentrations significantly inhibited the chemotactic response of human peripheral lymphocytes (21) and natural killer (NK) cell activity in vitro (22). Different forms and doses of GHRH have different biological properties; GHRH (1-29), but not GHRH , at low concentrations stimulated, whereas high concentrations inhibited phytohemagglutinin (PHA)-induced lymphoproliferation, interleukin (IL)-2 secretion, and IL-2 receptor expression on activated human peripheral lymphocytes (23).…”

mentioning

confidence: 99%

Effects of [Norleucine²⁷]Growth Hormone-Releasing Hormone (GHRH) (1–29)-NH₂Administration on the Immune System of Aging Men and Women¹

Khorram

Yeung

et al. 1997

The Journal of Clinical Endocrinology & Metabolism

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Aging in humans is associated with the decline of functional activities of the GH-insulin-like growth factor I (IGF-I) axis and the immune system. Because lymphocytes express GH-IGF-I, as well as GHRH and their respective receptors, restoration of this axis in ageadvanced individuals, by the administration of GHRH, may enhance immune cell function. This hypothesis was tested by a single blind randomized placebo-controlled trial of 5 months duration, in which healthy elderly subjects (10 women, 9 men) self-administered sc nightly placebo for 4 weeks, followed by 16 weeks of [norleucine 27 ]GHRH (1-29)-NH 2 at a dose of 10 g/kg. Fasting (0800 h-0900 h) blood samples were obtained for immune studies and for measurements of serum concentrations of IGF-I and soluble interleukin (IL)-2 receptor. GH pulsatility was determined in blood samples obtained at 10-min intervals for 12 h (2000 h-0800 h). Freshly isolated peripheral lymphocytes were analyzed by flow cytometric analysis for determination of lymphocyte subsets and monocytes. Mitogen stimulation responses, natural killer cell number and cytotoxicity, basal and stimulated IL-2 secretion from cultured lymphocytes, and IL-2 and IL-2R messenger RNA expression were measured. These studies were conducted at baseline, after placebo, and during GHRH analog administration at 4 and 16 weeks.Treatment with GHRH analog resulted in a significant increase (107 and 70% in men and women, respectively) in the 12-h integrated GH secretion (P Ͻ .05) and serum IGF-I levels (28%) (P Ͻ .001) in both men and women by 4 weeks and lasted 12 weeks for IGF-I and 16 weeks for GH. Activation of the immune system occurred in both sexes within 4 weeks. A 30% increase (P Ͻ .001) in lymphocytes expressing the transferrin receptor (CD71) and in monocytes (CD14) (P Ͻ .05) occurred within 4 weeks. By 16 weeks, there was a significant increase (30%) in B cells (CD20) (P Ͻ .01), in cells expressing the T cell receptor ␣/␤ (20%) (P Ͻ .01), and T cell receptor ␥/␦ (40%) (P Ͻ .0001). There were no changes in the number of T cells (CD3), T cell subsets (CD4, CD8), or natural killer cell (CD57) over the treatment period. The increase in B cell number was associated with enhanced responsiveness (50%) to the B cell mitogens: pokeweed mitogen (P Ͻ .01 or better) and Staphylococus aureus cells (P Ͻ .001), and a transient increase at 4 weeks in circulating IgG (P Ͻ .0001), IgM, and IgA (P Ͻ .001). T cells were functionally activated, as evidenced by a 50% increase in responsiveness to phytohemagglutinin (P Ͻ .01 or better), 70% increase in the number of lymphocytes expressing the IL-2 receptor (IL-2R) (CD25) (P Ͻ .001), and enhanced IL-2R messenger RNA expression and basal IL-2 secretion (50%) (P Ͻ .05) at 16 weeks of treatment. Furthermore, circulating soluble IL-2 receptor rose significantly (15%) (P Ͻ .05) within 4 weeks of treatment and remained elevated for the duration of the study. There were no sex differences in the immune response to GHRH analog and no adverse effects. These results indicate...

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Effect of Growth Hormone-Releasing Hormone on Human Peripheral Blood Leukocyte Chemotaxis and Migration in Normal Subjects

Cited by 21 publications

References 17 publications

Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia

Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia

The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1

Effects of [Norleucine²⁷]Growth Hormone-Releasing Hormone (GHRH) (1–29)-NH₂Administration on the Immune System of Aging Men and Women¹

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Effect of Growth Hormone-Releasing Hormone on Human Peripheral Blood Leukocyte Chemotaxis and Migration in Normal Subjects

Cited by 21 publications

References 17 publications

Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia

Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia

The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1

Effects of [Norleucine27]Growth Hormone-Releasing Hormone (GHRH) (1–29)-NH2Administration on the Immune System of Aging Men and Women1

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Effects of [Norleucine²⁷]Growth Hormone-Releasing Hormone (GHRH) (1–29)-NH₂Administration on the Immune System of Aging Men and Women¹