BioMetals 12: 347–352, 1999. © 2000 Kluwer Academic Publishers. Printed in the Netherlands. 347 Effect of zinc administration on thyrotropin releasing hormone-stimulated prolactinemia in healthy men Ana Val´ eria B. Castro 1 , Berenice B. Mendonça 2 , Walter Bloise 2 , Tadao Shuhama 3 & Jos´ e Brandão-Neto *4 1 Unidade de Endocrinologia e Metabologia, Faculdade de Medicina, UNESP, Botucatu, São Paulo, Brazil 2 Unidade de Endocrinologia, Faculdade de Medicina, USP, São Paulo, Brazil 3 Laborat´ orio de Qu´ ımica Anal´ ıtica, Faculdade de Ciências Farmacêuticas, USP, Ribeirão Preto, São Paulo, Brazil 4 Unidade de Endocrinologia e Metabologia, Faculdade de Ciências da Sa´ ude, UnB, Bras´ ılia, DF, Brazil * Author for correspondence (E-mail: jbn@brnet.com.br.) Received 22 July 1999; accepted 5 August 1999 Key words: zinc tolerance test, thyrotropin tolerance test, prolactin secretion, healthy men Abstract Previous in vitro studies have demonstrated zinc (Zn ++ ) inhibition of basal and of potassium (K + ) or thyrotropin- releasing hormone (TRH)-stimulated prolactin (PRL) secretion, in a selective, reversible, and dose-dependent manner. Thus, Zn ++ may regulate physiologically pituitary PRL secretion. Furthermore, studies with patients with uremia, cirrhosis or prolactinoma, have shown the coexistence of hypozincemia and hyperprolactinemia and zinc supplementation did not correct hyperprolactinemia in these patients. In normal individuals Zn ++ administration produced controversial results on PRL secretion. Here, we investigated whether zinc administration affects TRH- stimulated PRL in healthy men. We found that Zn ++ administration does not change the TRH-stimulated PRL. Therefore, in normal conditions, Zn ++ does not inhibit TRH-stimulated prolactinemia. In addition, we found that acute increases of blood PRL and TRH do not alter blood Zn ++ levels. Introduction Zn ++ is virtually present in all tissues, including the brain, hypothalamus and pituitary (Vallee et al. 1993). LaBella et al. (1973) have shown that Zn ++ within bovine hypothalamic extracts inhibited in a dose- dependent manner PRL pituitary secretion, which was later confirmed by Login et al. (1983). In addition, Judd et al. (1984) and Cooper et al. (1987) found that Zn ++ reversibly inhibited PRL secretion stimulated by TRH and K + , respectively. Based on these findings, Koppelman (1988) proposed the hypothesis that Zn ++ and PRL were involved in a negative feedback regula- tory loop, similar to the one that exists for parathyroid hormone (PTH) and calcium (Ca ++ ). There are few in vivo studies about Zn ++ and PRL relationship, which resulted in controversial re- sults. In rats, hypozincemia was associated to normal (Root et al. 1979), high (Mansour et al. 1989) or low plasma PRL levels (Hafiez et al. 1989). In hu- mans, hypozincemia and hyperprolactinemia were ob- served in patients with hepatic cirrhosis (Morley et al. 1981), uremia (Caticha et al. 1996), prolactinoma (Madureira et al. 1993, 1999) and idiopathic hyper- prolactinemia (Koppelman et al. 1989). Mahajan et al. (1985) reported that normalization of zincemia in uremic patients supplemented with Zn ++ reduced their prolactinemia levels. However, these results were contrasted with other studies (Nishi et al. 1988; Kop- pelman et al. 1989; Travaglini et al. 1989; Bonomini et al. 1993). The objectives of the present study were to investi- gate the effect of acute Zn ++ administration on TRH- stimulated PRL secretion, and, inversely, the effect of acute increment of TRH and PRL on zincemia.