Influence of dopamine on the altered release of prolactin, luteinizing hormone, and follicle-stimulating hormone induced by interleukin-2 in vitro.
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 were 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 x 10(-5) M) 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 microM) significantly reduced pituitary PRL content. The addition of 0.187, 3.75, 15, or 60 microM DA to IL-2-induced PRL release. IL-2 (10(-15) M) produced a significant decrease in LH and FSH release. The combination of 3.75 or 15 microM DA plus IL-2 failed to alter the IL-2 suppressed LH release, whereas the addition of 0.187 microM DA to IL-2 blocked its suppressive influence, and 60 microM 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 microM DA. DA alone at relatively high concentrations of 30, 60, and 90 microM 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 x 10(-5) M) 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.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040, USA.
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Karanth
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Marubayashi
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McCann
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats
D007376:Interleukin-2; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine