Interleukin-2 Is a Potent Inhibitor of Ley dig Cell Steroidogenesis*

Abstract

Interstitial tissue of the testis consists of Leydig cells, macrophages, lymphocytes, plasma cells, mast cells and fibroblasts. Previously we have reported that interleukin-1 (IL-1) inhibits Leydig cell androgen production. In the present study, the effect of IL-2 was investigated. Leydig cells (10(5) cells/ml) from adult Sprague-Dawley rats were cultured with or without IL-2 for 24 h. After medium changes, human CG (hCG), 8-bromo-cAMP, or forskolin was added with or without IL-2. Cultures were continued for an additional 24 h, and testosterone and cAMP levels were measured. IL-2 up to 100 U/ml had no effect on basal testosterone production. hCG-stimulated testosterone formation was inhibited in a dose-dependent manner by the addition of IL-2. IL-2 in a concentration of 100 U/ml decreased hCG-induced testosterone formation from 49.6 +/- 3.6 ng/ml (mean +/- SE) to 8.5 +/- 4.2 ng/ml. The hCG dose-response curve was shifted to the right by the addition of IL-2. Maximal testosterone production in response to hCG was reduced 40% in the presence of IL-2 (50 U/ml) without alteration of median effective dose (ED50). IL-2 also inhibited hCG-induced cAMP formation and 8-bromo cAMP- and forskolin-stimulated testosterone production. However, IL-2 did not alter the binding of [125I]hCG to purified Leydig cells. Furthermore, IL-2 significantly inhibited the conversion of 20-OH-cholesterol, 22-OH-cholesterol, pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone to testosterone but did not alter the conversion of dehydroepiandrosterone and androstenedione to testosterone. Our results suggest that a T cell growth factor, IL-2, is a potent inhibitor of steroidogenesis. IL-2 may play a paracrine role in modulating Leydig cell function.

Immunocytochemical Evidence for Interleukin-2 Receptor Regulation on Rat Anterior Pituitary and Adrenal Cells.

“…IL-2-induced increase in ATR-18 immunostaining observed in this study is almost comparable with that reported about the lymphocytes [10,14,23,30]. It is of value to be indicated that IL-2 used in this study was at the half-maximum effective concentration which induced corticosterone biosynthesis in our previous adrenal cell culture study [12]. In this study, we compared the time courses of IL-2 stimulated prostaglandin E2, cyclic AMP and corticosterone synthesis in dispersed rat adrenal cells and found that prostaglandin E2 synthesis began to increase within an hour but the stimulation of cyclic AMP and corticosterone synthesis needed more than 12 hr to be induced [27].…”

“…Among them, IL-2, originally identified as a T cell growth factor, has been reported to affect neuroendocrine functions, stimulating the pituitary-adrenocortical (P-A) axis [4,5,[7][8][9]17] and catecholamine release [7], and suppressing luteinizing hormone [29], testosterone [12] and melatonin levels [16]. No influence was reported on insulin levels [7], and effects on pituitary growth hormone, prolactin, thyroid-stimulating hormone, and folliclestimulating hormone releases are not conclusive [15,16,29].…”

Novel insights into the neuroendocrinology of critical illness

“…A role for in¯ammatory cytokines (IL-1 and IL-2) is possible, as suggested by experimental studies (74,75). It may be considered appropriate that the secretion of anabolic androgens be switched off in circumstances of acute stress, in order to reduce the consumption of energy and substrates for, at that time at least, less vital functions.…”

The pıtuıtary-gonadal-thyroıd and lactotroph axes ın crıtıcally ıll patıents

“…The reason for decreased T is the inhibition of testicular androgenesis or central LHRH secretion or both. Cytokines have been shown to take part in either situation [17,18]. Our patients had high CRP concentrations and APACHE II scores that prove the presence of inflammation and disease severity.…”