Physiology and Therapeutic Potential of the Thymic Peptide Thymulin
Paula C. Reggiani, Jose I. Schwerdt, Gloria M. Console, Eduardo A. Roggero, Mireille Dardenne and Rodolfo G. Goya
Affiliation: INIBIOLP, Faculty of Medicine, UNLP, CC 455; (zip 1900) La Plata, Argentina.
Keywords: Thymulin, neuroendocrine system, anti-inflammatory, nude mice, synthetic gene, gene therapy, regulatable promoters.
Thymulin is a thymic hormone exclusively produced by the epithelial cells of the thymus. After its discovery and initial characterization
in the ‘70s, it was demonstrated that the production and secretion of thymulin are strongly influenced by the neuro-endocrine
system. Conversely, a growing body of evidence, to be reviewed here, suggests that thymulin is a hypophysiotropic peptide. Additionally,
a substantial body of information pointing to thymulin and a synthetic analog as anti-inflammatory and analgesic peptides in the central
nervous system brain and other organs will be also reviewed. In recent years, a synthetic DNA sequence encoding a biologically active
analog of thymulin, metFTS, was constructed and cloned in a number of adenovectors. These include bidirectional regulatable Tet-Off
vector systems that simultaneously express metFTS and green fluorescent protein and that can be down-regulated reversibly by the addition
of the antibiotic doxycycline. A number of recent studies indicate that gene therapy for thymulin may be an effective therapeutic
strategy to prevent some of the hormonal and reproductive abnormalities that typically appear in congenitally athymic (nude) mice, used
as a suitable model of neuroendocrine and reproductive aging. Summing up, this article briefly reviews the publications on the physiology
of the thymulin-neuroendocrine axis and the anti-inflammatory properties of the molecule and its analog. The availability of novel
biotechnological tools should boost basic studies on the molecular biology of thymulin and should also allow an assessment of the potential
of gene therapy to restore circulating thymulin levels in thymodeficient animal models and eventually, in humans.
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