Anterior pituitary hormone control by interleukin 2.

Abstract

Several monokines, proteins secreted by monocytes and macrophages, alter release of hormones from the anterior pituitary. We report here the ability offemtomolar concentrations of interleukin 2 (IL-2), a lymphokine released from T lymphocytes, to alter directly pituitary hormone release. The effects of concentrations of IL-2 ranging from 10-i7 to 10-9 M on anterior pituitary hormone release were evaluated in vitro. Hemipituitaries were preincubated in 1 ml of KrebsRinger bicarbonate buffer (KRB) followed by incubation for 1 or 2 hr with KRB or KRB containing different concentrations of IL-2. This was followed by incubation for 30 min in 56 mM potassium medium to study the effect ofpretreatment with IL-2 on subsequent depolarization-induced hormone release. Prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticotropin (ACTH), growth hormone (GH), and thyrotropic hormone (TSH) released into the incubation medium were measured by radioimmunoassay. IL-2 stimulated the basal release of PRL at 1 or 2 hr but suppressed the subsequent depolarization-induced PRL release, perhaps because the readily releasable pool of PRL was exhausted. The minimal effective dose (MED) was 10-15 M. Conversely, IL-2 significantly suppressed the basal release of LH and FSH at 1 or 2 hr, with a MED of 10-16 M, thus demonstrating a reciprocal action of the cytokine on lactotrophs and gonadotrophs. The subsequent depolarization-induced release of LH and FSH was suppressed, indicative of a persistent inhibitory action of IL-2. IL-2 stimulated ACTH and TSH release at 1 hr and the MEDs were 10-12 and 10-1' M, respectively. Conversely, IL-2 significantly lowered the basal release of GH at 1 hr, with a MED of 10-'s M. The release of GH was not altered at 2 hr. The high potassium-induced release of ACTH, TSH, and GH was not affected. The results demonstrate that IL-2 at picomolar concentrations affects the release of anterior pituitary hormones. This cytokine may serve as an important messenger from lymphocytes exerting a direct paracrine action on the pituitary by its release from lymphocytes in the gland or concentrations in the blood that reach the gland may be sufficient to activate it.Bidirectional intercellular communication between the neuroendocrine and immune systems is firmly established (1, 2). The interplay between these systems is believed to be mediated by proteins termed cytokines (3). Interleukin 2 (IL-2) is a lymphokine, synthesized and secreted by T lymphocytes activated by antigen or mitogen (4,5). It is a glycoprotein (15.5 kDa) that stimulates the proliferation of T cells, B cells, natural killer cells, and lymphocyte-activated killer cells (3). IL-2 has been reported to enhance the expression of the proopiomelanocortin (POMC) gene by cultured normal and pituitary tumor (AT-20) cells (6). A similar activation of POMC mRNA has already been demonstrated for IL-1 (7). IL-2 increased plasma corticotropin (ACTH) and glucocorticoid levels when injected into patients with cancer or acquired immuno...

The Impact of Escitalopram on IL-2-Induced Neuroendocrine, Immune, and Behavioral Changes in Patients with Malignant Melanoma: Preliminary Findings

“…First, in response to IL-2 administration, over time, there appears to be an enhancement of ACTH response. This increasing ACTH secretion is congruent with previous preclinical and clinical studies showing that IL-2 administration is associated with activation of stress-responsive neuroendocrine pathways [corticotropin releasing hormone (CRH) and HPA axis] (Butler et al, 1989;Denicoff et al, 1987;Hanisch et al, 1994;Karanth and McCann, 1991;Katahira et al, 1998;Raab et al, 1999;Raber et al, 1995;Spina et al, 1994). We postulate that this enhanced ACTH response may be related to IL-2-induced dysregulation of glucocorticoid receptor function at the level of the pituitary, hypothalamus, and/or hippocampus (Raison and Miller, 2003a) and possibly due to interactions between glucocorticoid receptors and innate immune signaling pathways and/or activation of T-cell responses involving DNA binding of nuclear factor of activated T cells and activation protein-1.…”

The Effect of Interleukin-2 on the Release of Gonadotropin and Prolactin in Vivo and in Vitro.

“…Karanth and McCann reported the ability of IL-2 to modulate the release of anterior pituitary hormones by a direct action on hemipituitaries incubated in vitro. They indicated that IL-2 augmented the basal release of PRL, TSH and ACTH and attenuated the basal release of LH, FSH and CH [17]. In the present study, we demonstrate the opposite effect of IL-2.…”

“…There is increasing evidence that interleukins directly act at the pituitary level to modulate the release of anterior pituitary hormones [1,7,8,12,17]. Numerous in vitro studies have addressed the direct effects-with confusing results [1].…”

“…IL-2 was also reported to affect the release of anterior pituitary hormones at the level of the pituitary gland [17]. It is therefore not surprising that IL-2 may play a physiological role in the control of anterior pituitary hormone secretions at the …”

Expression of IL-6 mRNA in normal rat and human pituitaries and in human pituitary adenomas.

“…Various hormones may influence lymphocyte function (1). Conversely, secretory products of macrophages and lymphocytes modulate endocrine function (3)(4)(5)(6)(7)(8). Interleukin-6 (IL-6), for example, is produced by the anterior pituitary (9-11).…”