Human lymphocyte production of immunoreactive thyrotropin.

Abstract

Interferon-a inducers were previously shown to cause human lymphocyte production of a corticotropin (ACTH)-like peptide. Thyrotropin (TSH) was not produced under these conditions. In contrast, this report shows that a T-cell mitogen (staphylococcal enterotoxin A), which does not induce the ACTHlike peptide, caused human lymphocyte production of an immunoreactive (ir) TSH. Lymphocyte synthesis of the ir TSH was first detectable at 24 hr, peaked at 48 hr, and thereafter declined. NaDodSO4/polyacrylamide gel electrophoresis of intrinsically radiolabeled lymphocyte-derived ir TSH showed radiolabeled peaks at 80, 50, and 26 kilodaltons. These peaks presumably correspond to trimeric, dimeric, and monomeric TSH-like proteins, respectively. Acid treatment and reduction caused the ir TSH to migrate as a 14-kilodalton peak with a 12-kilodalton shoulder in a gel filtration column run in 6 M guanidineHCI. Thus, the ir TSH seemed to be composed of subunits with molecular masses corresponding to those of the (3 and a chains of human TSH, respectively. The ir TSH appeared to be glycoprotein because it bound to a concanavalin A affinity column. Taken together these data suggest that in addition to ACTH, human lymphocytes can also produce a TSH-like substance.In general, interactions between the immune and neuroendocrine systems have been studied in terms of hormone effects on immune functions. Recently we have found that the reverse situation may also occur. Specifically, lymphocytes infected with Newcastle disease virus were found to synthesize a peptide that is antigenically, structurally, and functionally related to, if not identical with, the neuroendocrine hormone corticotropin (ACTH) (1-3). In vitro and in vivo (in hypophysectomized animals) this lymphocyte-derived ACTH caused adrenal cell release of corticosteroids (1, 2, 4). Conversely, a pituitary ACTH preparation directly inhibited in vitro antibody production (5). These results suggest that a complete regulatory loop may operate between the immune and neuroendocrine systems through peptide hormones that are common to both systems. As a means to determine the spectrum of peptides that may be common to these two systems, mitogen-stimulated lymphocytes were screened by immunofluorescence for the production of various neuroendocrine hormones. This report describes the production and characterization of an immunoreactive thyrotropin (ir TSH) produced by T-cell mitogen (staphylococcal enterotoxin A, SEA)-stimulated lymphocytes. MATERIALS AND METHODSReagents. Electrophoretically pure SEA was kindly provided by the Microbial Biochemistry Branch of the Food and Drug Administration (Cincinnati, OH) (6). Rabbit anti-human TSH (3 chain antiserum and the purified human TSH ( chain were reference reagents generously donated by the National Pituitary Agency (National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases).Cell Culture and Mitogen Treatment. Human peripheral lymphocytes were purified from whole blood buffy coats by centrifugation on a Ficoll-Hy...

Evidence that somatostatin is localized and synthesized in lymphoid organs.

“…Examples include adrenocorticotropin hormone (24), f3-endorphin (25), vasoactive intestinal polypeptide (26,27), thyrotropin (28), chorionic gonadotropin (29), follicle-stimulating hormone (30), luteinizing hormone (30), growth hormone (31), and finally growth-hormone-releasing hormone (32). In this latter connection, it is tempting to speculate that growth-hormone-releasing hormone and SRIH might have antagonistic paracrine actions on immune cells just as they affect the release of growth hormone from the pituitary gland in an opposing manner.…”

An intrinsic thyrotropin-mediated pathway of TNF-α production by bone marrow cells

“…Studies by Smith and coworkers demonstrated TSH secretion by human peripheral blood leukocytes stimulated with Staphylococcus enterotoxin A. 1 Subsequent work revealed TSH gene expression in activated mouse spleen cells, 2 and secretion of TSH by mouse splenic mononuclear cells, in particular dendritic cells (DCs) and to a lesser extent T cells and B cells. 3 Human peripheral blood leukocytes have been shown to bind TSH in radiolabeled binding studies 4,5 and by flow cytometry using biotin-labeled TSH.…”

Characterization of a novel set of resident intrathyroidal bone marrow-derived hematopoietic cells: potential for immune-endocrine interactions in thyroid homeostasis

“…Such biological intersections are particularly evident between many aspects of the immune system and the neuroendocrine system. Thus, a number of classical neuroendocrine hormones are produced by the cells of the human and murine immune systems (Smith and Blalock, 1981;Smith et al, 1983;Stephanou et al, 1990;Hiestand et al, 1986;Hattori et al, 1990;Wang et al, 2003), and receptors for those are widely distributed across many types of hematopoietic cells (Wang et al, 2003;Chabaud and Lissitzky, 1997;Kruger et al, 1989;Coutelier et al, 1990;Hiruma et al, 1990;Bagriacik and Klein, 2000;Wang et al, 1997). The functional significance of those immune-endocrine circuits, though not fully evident, is nonetheless gradually becoming clear.…”