title: Modifications of thymulin titers in patients affected with prolonged low or high zinc circulating levels are independent of patients' age.
abstract: Thymulin (FTS) is a thymic hormone, the bioactivity of which depends on zinc (Zn) incorporation in its molecule (FTS bioactive form: Zn-FTS). Many hormones (T3, GH, PRL, Gn-RH 6-endorphin) and Zn are able to increase thymus trophism and Zn-FTS circulating levels, even in old animals, suggesting that age dependent thymic involution is a reversible phenomenon. FTS circulating levels and thymus trophism are age-dependent. In fact, the decrease of Zn-FTS starts from the age of 10-20 years and proceeds progressively. In 19 uremic patients on hemodialysis (mean age +/- SD: 44.7+/-11.7, range 29-60 years) and 58 patients with prolactinoma (mean age 31+/-7; range 18-58) we found low Zn-FTS levels (expressed as scalar dilution in form of 1/log(2)): 1.5+/-0.5 and 2.1+/-0.7, respectively, vs normal age and sex matched controls: 2.9+/-0.4 and 3.6+/-0.3, respectively; p<0.01. On the contrary, in 41 acromegalic patients (mean age 43+/-12; range 20-63 years) Zn-FTS levels were elevated (4.5+/-0.7 vs controls: 2.8+/-0.3, p<0.01). In all these patients, age-related differences of Zn-FTS circulating levels were lost and Zn-FTS titers were homogeneously low or high according to Zn levels. In fact, in uremic patients and in patients with prolactinoma, Zn levels were low (79+/-26 microg/dl and 82+/-23 microg/dl, respectively, vs control levels: 114+/-12 microg/dl, p<0.01), while They were high in acromegalic patients (141+/-44 microg/dl vs control levels: 112+/-11 microg/dl, p<0.01). After ZnSO(4) administration (400 mg per os/day) for six months. Zn levels increased over the normal range, both in patients with uremia and in patients with prolactinoma (136+/-15 microg/dl and 138+/-18 microg/dl, respectively; p<0.01). Also Zn-FTS levels increased homogeneously independently of age (5.2+/-0.7 and 5.3+/-0.8, respectively); p<0.01, both vs basal and control values; PRL circulating levels did not change. In 20 patients affected with prolactinoma and in 10 acromegalic patients, Zn and Zn-FTS decreased to the normal range, 6, or 12 months after surgical or pharmacological normalization of high PRL and GH circulating levels. In these patients, age-related titers of Zn-FTS were found, such as in controls.
  
  
  CONCLUSIONS
  (i) Reduced Zn-FTS levels in patients affected with uremia or prolactinoma and the increased Zn-FTS titers present in acromegalic patients are related to low and high Zn circulating levels, respectively, underlining the importance of Zn in regulating thymulin secretion. (ii) When spontaneous (or induced) hyper- or hypo-zincemia occurs, age-related differences of Zn-FTS titers are lost, suggesting that Zn may overcome the effect of age on thymic function.
authors.affiliation: Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, Via F. Sforza 35, I-20122 Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Travaglini
authors.forename: E
authors.initials: E
authors.lastname: Mocchegiani
authors.forename: C
authors.initials: C
authors.lastname: De Min
authors.forename: T
authors.initials: T
authors.lastname: Re
authors.forename: N
authors.initials: N
authors.lastname: Fabris