Influence of Dopamine on the Altered Release of Prolactin, Luteinizing Hormone, and Follicle-Stimulating Hormone Induced by Interleukin-2 in vitro

Abstract

Interleukin-2 (IL-2) alters the release of anterior pituitary hormones at femtomolar concentrations from hemipituitaries incubated in vitro. This cytokine significantly lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and stimulated prolactin (PRL) release, thus demonstrating a reciprocal action of the lymphokine on lactotrophs and gonadotrophs. Since dopamine (DA) is a powerful inhibitor of PRL release, in the present experiments we evaluated possible dose dependent effects of DA on IL-2-induced alterations of the release of PRL, LH, and FSH. Hemipituitaries were incubated with varying concentrations of DA, a combination of IL-2 plus DA, or a combination of haloperidol (1 × 10^–5M) with DA for 1 h, followed subsequently by incubation with medium containing only high potassium (K⁺) to study the effects on depolarization-induced hormone release. DA induced a dose-related, significant lowering of the basal PRL release with a minimal effective dose (MED) of less than 19 nM. The depolarization-induced PRL release was also inhibited, but the MED was 100-fold higher than the MED to inhibit basal PRL release. DA at much higher concentrations (30, 60, and 90 µM) significantly reduced pituitary PRL content. The addition of 0.187, 3.75, 15, or 60 µM DA to IL-2 (10^–15 M) blocked IL-2-in duced PRL release. IL-2 (10^–15M) produced a significant decrease in LH and FSH release. The combination of 3.75 or 15 µM DA plus IL-2 failed to alter the IL-2 suppressed LH release, whereas the addition of 0.187 µM DA to IL-2 blocked its suppressive influence, and 60 µM DA added to IL-2 produced an additive inhibitory effect. Thus, the interaction of IL-2 and DA is biphasic on LH release. The significant reduction of FSH release induced by IL-2 was blocked in the presence of 0.187, 3.75, 15, or 60 µM DA. DA alone at relatively high concentrations of 30, 60, and 90 µM suppressed basal LH and FSH release. The effects of DA on PRL, LH, and FSH at all doses tested were blocked by the DA receptor blocker, haloperidol which by itself at the concentration tested (1 × 10^–5M) had no effect. Thus, the actions of DA at all concentrations tested appear to be mediated via DA receptors. In conclusion, DA was capable of blocking the stimulatory action of IL-2 on PRL release and its inhibitory action on FSH release by a DA receptor mediated action. Only a relatively low concentration of DA (0.187 M) blocked the inhibitory action of IL-2 on LH release.

Immunoneuroendocrine Connectivity: The Paradigm of the Thymus-Hypothalamus/Pituitary Axis

“…Also, the IL-2 receptor ß chain has been detected and cloned from AtT20 cells [131]. The presence of the receptor in these cells is in agreement with previous studies showing the action of IL-2 on the secretion of these hormones [44,46]. Using a binding assay and a molecular biology approach, a TNF receptor has also been shown in the pituitary gland cells, such as the AtT20 corticotrophs and TtT/GF folliculostellate cells [132].…”

“…The release pattern of pituitary hormones after IL-2 stimulation closely mimics the alterations of pituitary hormone secretion in response to stress [44]. IL-2-induced PRL secretion is blocked by dopamine [46]. IL-2 enhances ACTH secretion in AtT20 cells [45] and stimulates PRL release from GH3 cells [48]; in the latter, antiestrogens inhibit IL-2-induced PRL secretion.…”

Regulation of Pituitary Function by Cytokines

“…They colocalize with PRL, GH [32] and ACTH [30]. It has been proven that IL-2 alters the secretion of these hormones [33,34,35]. However, there are contradictions regarding the effects of IL-2, and they appear to be species-specific and cell model-specific [36].…”

Effects of acute psychological stress on adhesion molecules, interleukins and sex hormones: implications for coronary heart disease

“…During anticipatory psychological stress, a reduction in plasma testosterone concentrations has been observed (Kreuz et al 1972;Schulz et al 1996), which may be mediated by stress-induced IL-1, IL-2 and IL-6 activation (Karanth et al 1992;Turnbull and Rivier 1995;Cannon 1998). Since testosterone inhibits IL-1 release in vitro (Li et al 1993) and suppresses IL-6 induced corticosterone release in rats (Papadopoulos and Wardlaw 2000), stressassociated reductions in testosterone plasma concentrations may disinhibit immune activation.…”