Thymulin Gene Therapy Prevents the Histomorphometric Changes Induced by Thymulin Deficiency in the Thyrotrope Population of Mice

Martines, Eliana; Reggiani, Paula C.; Schwerdt, José Ignacio; Goya, Rodolfo G.; Cónsole, Gloria M.

doi:10.1159/000322583

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…Immunoneutralization experiments lend support the idea that thymulin may be a physiologic mediator of the perinatal influence of the thymus gland on the maturation of the neuroendocrine axis. Thus, immunoneutralization of serum thymulin from age 1 to 33 days in normal C57BL/6 mice induced clear morphologic changes in most adenohypophysal endocrine cell populations [50][51][52] as well as a reduction in serum levels of gonadotropins, TSH, PRL and GH ( Fig. 1).…”

Section: Hypophysiotropic Activity Of the Hormone Thymulinmentioning

confidence: 90%

“…NTGT has also been reported to partially prevent the alterations that occur in some of the endocrine cell populations of nude mice after puberty. Thus, NTGT prevented the reduction in the number of gonadotrophs, thyrotrophs, corticotrophs and somatotrophs in adult nudes [51,[80][81][82]. NTGT also prevented, to a varying extent, changes in other histomorphometric parameters in the anterior pituitary of adult nudes.…”

Section: Neonatal Gene Therapy For Thymulin In Nude Micementioning

confidence: 99%

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Physiology and Therapeutic Potential of the Thymic Peptide Thymulin

Reggiani¹,

Schwerdt²,

Cónsole³

et al. 2014

CPD

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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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Section: Hypophysiotropic Activity Of the Hormone Thymulinmentioning

confidence: 90%

Section: Neonatal Gene Therapy For Thymulin In Nude Micementioning

confidence: 99%

Physiology and Therapeutic Potential of the Thymic Peptide Thymulin

Reggiani¹,

Schwerdt²,

Cónsole³

et al. 2014

CPD

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“…Thus, neonatal immunoneutralization of circulating thymulin in otherwise normal C57BL/6 mice induced significant morphologic alterations in most anterior pituitary endocrine cell populations [50,51] as well as a reduction in circulating levels of gonadotropins, thyrotropin, PRL and GH [ 51, 52 ; unpubl. obs. ].…”

Section: Hypophysiotropic Activity Of Thymulinmentioning

confidence: 99%

“…Thus, NTGT prevented the reduction in the number of gonadotrophs, thyrotrophs and corticotrophs in adult nudes [51,60,61] . NTGT also prevented, to a varying extent, changes in other histomorphometric parameters in the anterior pituitary of adult nudes.…”

Section: Neonatal Gene Therapy For Thymulin In Nude Micementioning

confidence: 99%

Thymulin-Based Gene Therapy and Pituitary Function in Animal Models of Aging

Reggiani¹,

Poch²,

Cónsole³

et al. 2011

Neuroimmunomodulation

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Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. After its discovery and initial characterization in the 1970s, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysiotropic peptide. Additionally, thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. In recent years, a synthetic DNA sequence coding for a biologically active analog of thymulin, metFTS, was constructed and cloned in different adenoviral vectors. These include bidirectional regulatable Tet-Off vector systems that simultaneously express metFTS and green fluorescent protein and that can be downregulated reversibly by the addition of the antibiotic doxycycline. A number of recent studies suggest that thymulin gene therapy may be a suitable therapeutic strategy to prevent some of the endocrine and reproductive alterations that typically appear in congenitally athymic (nude) mice, taken as a suitable model of neuroendocrine and reproductive aging. The present article briefly reviews the literature on the physiology of the thymulin-pituitary axis as well as on the new molecular tools available to exploit the therapeutic potential of thymulin.

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“…Thus, it was observed that thymulin stimulates PRL release in dispersed rat pituitary cells [9], whereas others have reported that thymulin inhibits PRL release in incubated rat pituitary fragments [8]. Furthermore, we have found in in vivo studies that thymulin is an important player in the communication of the thymus with the gonadotropic, corticotropic and thyrotropic axes [13,14,15,16]. …”

Section: Introductionmentioning

confidence: 99%

The Thymulin-Lactotropic Axis in Rodents: Thymectomy, Immunoneutralization and Gene Transfer Studies

Martines

Reggiani

Camihort³

et al. 2013

Neuroimmunomodulation

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Objectives: There is clear evidence on the existence of a thymus-pituitary axis which seems to be particularly important during perinatal life. In particular, the thymic peptide thymulin has been shown to be a relevant player in thymus-pituitary communication. Our goal was to explore the effect of thymulin on circulating prolactin (PRL) levels in different animal models. To this end we undertook a series of experiments in rats and mice, implementing adult thymectomy, thymulin immunoneutralization in normal C57BL/6 mice and neonatal thymulin gene therapy in nude mice. Methods: We assessed the impact of the above manipulations on PRL secretion and lactotrope morphology by measuring serum PRL by radioimmunoassay and by performing morphometric analysis of the lactotropic cell population in the anterior pituitary gland. Results: Adult thymectomy in female rats slightly increased serum PRL, an effect that was partially reversed by thymulin gene therapy. In mice, thymulin immunoneutralization from birth to age 32 days reduced serum PRL both in males and females. Thymulin immunoneutralization induced a significant (p < 0.01) decrease in lactotrope cell density (CD) and volume density (VD) without changes in cell size (CS). Neonatal thymulin gene therapy markedly increased serum thymulin (p < 0.01) and lactotrope CD, CS and VD in nude mice of both sexes. Conclusions: Our findings suggest a modulatory effect of thymulin on the lactotrope cell population and on serum PRL, particularly during early life.

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Thymulin Gene Therapy Prevents the Histomorphometric Changes Induced by Thymulin Deficiency in the Thyrotrope Population of Mice

Cited by 6 publications

References 31 publications

Physiology and Therapeutic Potential of the Thymic Peptide Thymulin

Physiology and Therapeutic Potential of the Thymic Peptide Thymulin

Thymulin-Based Gene Therapy and Pituitary Function in Animal Models of Aging

The Thymulin-Lactotropic Axis in Rodents: Thymectomy, Immunoneutralization and Gene Transfer Studies

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