Effects of suramin on hormone release by cultured rat anterior pituitary cells

Abstract

Suramin is a polyanionic compound which has been used in the treatment of trypanosomiasis and acquired immunodeficiency syndrome (AIDS), while preliminary success has been reported in the treatment of cancer. However, suramin also causes adrenal insufficiency. We have previously reported that suramin selectively inhibited corticotropin (ACTH)-stimulated corticosterone release by dispersed adrenal cells in a dose-dependent manner via a direct interaction with the ACTH molecule. The present study was undertaken in order to investigate the effect of suramin on hormone release by dispersed rat anterior pituitary cells. Suramin at a concentration of 100 μM inhibited both basal and secretagogue-stimulated ACTH release by cells cultured in minimal essential medium (MEM) only, while it had no effect on ACTH release by cells cultured in MEM + 10% fetal calf serum (FCS) or MEM + 0.1% bovine serum albumin (BSA). In addition, suramin also caused a parallel decrease of prolactin (PRL) and growth hormone (GH) release by cells cultured in MEM only, suggesting a toxic, rather than a selective effect of suramin on anterior pituitary cells cultured in MEM only. In addition, suramin potentiated the effect of thyrotropin-releasing hormone (TRH) on PRL release by cells cultured in MEM + 10% FCS and suppressed the inhibitory effect of dopamine (DA) on PRL release by cells cultured in MEM + 10% FCS and in MEM + 0.1% BSA. Comparable suppressive effects of suramin on growth hormone-releasing hormone (GHRH)-stimulated and somatostatin (SRIH)-inhibited GH release were found in cells cultured in MEM + 0.1% BSA but not in cells cultured in MEM + 10% FCS. Finally, suramin blocked the bovine follicular fluid (bFF)-mediated inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release by cells cultured in MEM + 10% FCS, probably via a direct interaction with inhibin in the bFF. From these results we conclude that: (1) the effect of suramin on the hypothalamo-pituitary-adrenal axis appears to be mainly restricted to the adrenals, because its inhibitory effects on ACTH release by dispersed anterior pituitary cells appears to be nonspecific, being prevented by adding 0.1% BSA or 10% FCS. (2) The effect of suramin on PRL and GH release in response to their secretagogues is variable and dependent on the protein environment of the cells. (3) The effect of suramin on bFF-mediated inhibition of FSH and LH release by pituitary cells seems to be rather specific through an interaction with inhibin and abolishment of its inhibitory effects on FSH and LH release.