GH, GH Receptor, GH Secretagogue Receptor, and Ghrelin Expression in Human T Cells, B Cells, and Neutrophils

Abstract

We examined GH and GH receptor expression in human leukemic cell lines and leukocytes of normal subjects to elucidate the cell types expressing GH and GH receptor, the individual variations of their expressions, their correlation and the relationships with serum IgG and IGF-I concentrations. In addition, the expression of GH secretagogue receptor, which enhances GH secretion from the anterior pituitary by synthetic GH secretagogues and that of its endogenous ligand, ghrelin, were also examined in these immune cells. GH expression in human leukemic cell lines was observed mainly in B cell lines at both the mRNA and protein level [3.8 +/- 0.2 pg/10(6) cells in Raji and 19.9 +/- 3.3 pg/10(6) cells in Daudi vs. negligible in T cell lines (Jurkat and Hut-78) and in myeloid cell lines (K-562 and HL-60)]. B cells in normal subjects were also found to be the major immune cells expressing GH mRNA, with significant individual variation. GH receptor mRNA expression was detectable in all human leukemic cell lines, although the expression level varied widely among the cell lines and was weaker than that in the liver. On the other hand, GH receptor mRNA expression was mainly found in B cells, with marked individual variation in normal subjects. There was a positive correlation between the mRNA expressions of GH and GH receptor in B cells of normal subjects (r = 0.89; P < 0.001). Single cell RT-PCR revealed that some B cells expressed both GH and GH receptor transcripts, and others expressed only GH. GH/GH receptor expression levels in B cells did not show any correlation with serum IgG and IGF-I levels in normal subjects. Expression of GH secretagogue receptor and ghrelin was detectable in all immune cells regardless of the maturity and cell types with great individual variations. In summary, GH secreted from B cells may act locally on their own receptors, and their variable expressions may be related to individual immune functions. Widespread distribution of ghrelin and GH secretagogue receptor in human immune cells may indicate unknown biological functions other than enhancing GH secretion in the immune system.

Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis

“…In pituitary-intact rats, treatment with ghrelin reduced the colitis-evoked increase in mucosal concentration of those indices of inflammation. This anti-inflammatory effect of ghrelin could be a result of its direct action on ghrelin receptors present on the membranes of the immune system cells [64,65]. However, experiments performed on hypophysectomized rats indicated that the anti-inflammatory effect of ghrelin in acetic acid-induced colitis is related to the release of endogenous growth hormone and IGF-1.…”

Growth Hormone Resistance—Special Focus on Inflammatory Bowel Disease

“…Within the subset of T cells, GHR expression is the lowest in cluster of differentiation 4+ T cells. Not only do immune cells express GHR, indicating that they may respond to GH, many immune cells also express GH [127]. In agreement with the pattern of GHR expression, GH gene and protein expression is highest in B cells, although the level of secreted GH was near the detection limit.…”

“…The expression of both GH and GHR by B cells indicates that GH action in these cells may be through an autocrine/paracrine pathway. The authors did not find any correlation between B cell GH/GHR expression and serum Immunoglobulin G or IGF-1, respectively [127]. …”

Molecular Ghrelin System in the Pancreatic Acinar Cells: The Role of the Polypeptide, Caerulein and Sensory Nerves

“…The presence of mRNA signal for GHS-R and/or its production has been demonstrated in an organism both in the central structures [57,69,70] and in the peripheral tissues [24,70,71,72]. Genetic expression of GHS-R type 1a has been identified in the thyroid, pancreas, spleen, cardiac muscle and adrenal gland.…”

“…On the other hand, GHS-R type 1b has been widely detected in the following systems: digestive, respiratory, cardiovascular, endocrine, reproductive, excretory and immune. Moreover, it has also occurred in the skin, breast, buccal mucosa, muscle and fat tissue [24,70,71,72]. …”