Macrophage migration inhibitory factor production by Leydig cells: evidence for a role in the regulation of testicular function.

Abstract

Macrophage migration inhibitory factor (MIF), described originally as a product of activated T lymphocytes, recently has been found to be released by monocytes/macrophages and the anterior pituitary gland. Immunohistochemical studies of the adult rat testis using an affinity-purified polyclonal antimurine MIF antibody demonstrated strong staining for MIF in Leydig cells and their putative precursors. Peritubular myoid cells and the seminiferous epithelium were negative for MIF staining; however, a weak reaction around the heads of elongated spermatids also was observed. The expression of MIF messenger RNA and protein in whole rat testis was demonstrated by Northern blot and Western blot analyses, respectively. Both MIF messenger RNA and protein immunoreactivity in Leydig cells was observed in testes obtained from long term hypophysectomized rats. Significant concentrations of intracellular MIF were detected in lysates of the TM3 Leydig cell line (7.23 +/- 2.6 pg/microgram protein), and testicular interstitial fluid contained 14.7 +/- 1.6 ng/ml MIF protein, as measured by MIF-specific enzyme-linked immunosorbent assay. To gain insight into the possible biological role of MIF in the testis, cultures of adult rat seminiferous tubules and purified Leydig cells were incubated together with recombinant murine MIF (rMIF). Neither rMIF (50 ng/ml) nor a neutralizing anti-MIF antiserum was found to affect basal or LH-stimulated Leydig cell steroidogenesis in vitro. However, a dose-dependent decrease in the secretion of inhibin by the seminiferous tubules was observed at rMIF concentrations ranging from 10-100 ng/ml. Taken together, these data indicate that Leydig cells produce MIF in vivo and suggest an important regulatory role for this newly discovered mediator of testicular function.

Urine macrophage migration inhibitory factor (MIF) in children with urinary tract infection: a possible predictor of acute pyelonephritis

“…It is constitutively expressed by a variety of cell types and in many tissues [21][22][23][24][25][26][27][28]. Renal MIF mRNA and protein expression is upregulated in different types of experimental kidney disease [29][30][31][32].…”

Macrophage migration inhibitory factor: Cytokine, hormone, or enzyme?

“…Bernhagen and his coworkers recently reported that MIF catalyzes the reduction of disulfides in insulin and small molecular weight substrates via transhydrogenase reactions (Kleeman et al 1998a). The three-dimensional structure of MIF is unlike any other cytokine (Sun et al 1996;Suzuki et al 1996b;Kato et al 1996), Weiser et al 1989Onodera et al 1997Juttner et al 1998Swope et al 1998Bacher et al 1996Apte et al 1998Mikayama et al 1993Calandra et al 1995Waeber et al 1997Meinhardt et al 1996Rosengren et al 1996Rosengren et al 1997Kleeman et al 1998 but bears striking similarity to the global architecture and local active site of two microbial enzymes (Subramanya et al 1996). These biological and structural observations have raised the intriguing possibility that MIF may have a dual role as a cytokine/hormone and enzyme.…”

Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders

“…Recently, many reports have also suggested that MIF is considered to be an endocrine factor. 28,29 Interestingly, MIF has been demonstrated to have various kinds of catalytic activities; for example, tautomerase and oxidoreductase activity. 27,30,31 MIF is ubiquitously expressed in both immune and other cells, including various kinds of local tissues.…”