Anterior pituitary hormone control by interleukin 2.

Several monokines, proteins secreted by monocytes and macrophages, alter release of hormones from the anterior pituitary. We report here the ability of femtomolar 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(-17) to 10(-9) M on anterior pituitary hormone release were evaluated in vitro. Hemipituitaries were preincubated in 1 ml of Krebs-Ringer 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 of pretreatment 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(-15) M, respectively. Conversely, IL-2 significantly lowered the basal release of GH at 1 hr, with a MED of 10(-15) 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.