Metallothionein Synthesis in Foetal, Neonatal and Maternal Rat Liver

Abstract

The synthesis of hepatic metallothionein relative to other cytosol proteins was measured by [35S]cysteine incorporation in foetal, neonatal and pregnant rats. The relative rate of hepatic metallothionein synthesis reached a maximum in foetal liver on days 18 -21 of gestation. Metallothionein synthesis then declined until weaning, when adult levels were established. The rate of metallothionein synthesis was greater in pregnant rats at term than in nulliparous rats.To determine if circulating inducing agents could play a role in the regulation of metallothionein synthesis in foetal liver we treated pregnant rats with inducers at a time prior to the normal rise in foetal liver metallothionein synthesis. Injections of copper, cadmium or hydrocortisone to 17-day-pregnant dams failed to induce foetal metallothionein synthesis. In contrast, zinc injection to the dam was an effective inducer in the foetuses.Maternal laparotomy (performed to expose the foetus for direct injection of inducers) induced foetal metallothionein synthesis. Metallothionein synthesis in the livers of 17-day-gestation dams was induced by all metal injections and laparotomy but, surprisingly, not by hydrocortisone injection. Maternal adrenalectomy did not influence the subsequent normal elevation in foetal or maternal metallothionein synthesis. These results, in conjunction with previous reports, suggest that mobilization of zinc in serum during late gestation may regulate foetal and maternal changes in metallothionein synthesis.Metallothioneins are low-molecular-weight, cysteine-rich proteins normally found in association with Zn2 Metallothioneins have been found in increased concentration, relative to adults, in foetal and neonatal rat liver 211. Porter [22] has demonstrated that 'neonatal mitochondrocuprein', a coppercontaining high-molecular-weight complex in the particulate fractions of foetal bovine liver is, in fact, a polymeric form of metallothionein. The large amounts of metallothionein present in these early developmental stages correlate with increased copper and zinc concentrations in the liver. Such elevated concentrations of metallothionein, binding copper and zinc in foetal and neonatal liver, suggest that this protein may play an important role in metal storage or transport during development [23]. We now report increased levels of metallothionein biosynthesis in rat liver during both foetal and neonatal development. We also report on the inducibility of hepatic metallothionein in response to varying metal, hormone, and/or physiological conditions in rat pups and dams during these developmental stages. MATERIALS A N D METHODS MaterialsMaterials were obtained from the following sources : Tris, hydrocortisone sodium succinate, hydrocortisone, and Sephadex G-75 were from Sigma; [35S]cystine (427 Ci/mmol and lo9Cd (chloride salt, carrier-free) were from New England Nuclear; sucrose and guanidine/HCl were from Schwarz Mann; 2-mercaptoethanol was from Fisher; 5,5'-dithiobis-(2-nitrobenzoic acid) was from Aldrich; cadmium chloride was ...

Arctic char (Salvelinus alpinus) metallothionein: cDNA sequence, expression, and tissue‐specific inhibition of cadmium‐mediated metallothionein induction by 17β‐estradiol, 4‐OH‐PCB 30, and PCB 104

“…The higher MT levels in kidney than liver on day 7 would thus indicate differences in posttranscriptional regulation in these two organs. This is in agreement with the observations on Antarctic icefish and the developmental MT regulation in rat [25, 29, 30]. Further studies are necessary to clarify the mechanisms regulating the observed differences in posttranscriptional regulation of MT in fish.…”

Metallothioneins pattern during ontogeny of coastal dolphin, Pontoporia blainvillei, from Argentina

“…These dolphins are the result of spontaneous abortions, and being these relevant situations of stress, probably it was the cause of the lack of a defined pattern regarding adult females of this group geographic. In relation to the pregnant female, coincidentally with previous studies in pregnant women (Mc Ardle and Ashworth, 1999) and rats (Piletz et al, 1983), MT concentrations are higher than nonpregnant females.…”

Evidence for differences in the post-transcriptional regulation of rat metallothionein isoforms

“…For instance, it has been shown that in itro translation of polyribosomal mRNA from Cd-treated rats did not consistently give greater synthesis of MT protein than that from control rats [28]. In addition, studies of rat development have shown that, after birth, total MT-1 and MT-2 mRNA levels remained high, although MT protein levels [12,13], and MT synthesis rates [29], decreased. Furthermore, during the induction of MT by Zn, MT mRNA levels remained higher than control values for up to 36 h, whereas the rate of synthesis of MT was the same as the control by 24 h [30].…”