Studies on the Gonadotropin-Releasing Activity of Thymulin: Changes With Age

Brown, Oscar A.; Sosa, Yolanda E.; Dardenne, Mireille; Pleau, Jean-Marie; Goya, Rodolfo G.

doi:10.1093/gerona/55.4.b170

Cited by 24 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thymulin is known to possess hypophysiotropic activity in vitro (3)(4)(5)15,29) and therefore may act directly on the adenohypophysis in vivo, modulating the response of the gland to hypothalamic or other secretagogues or inhibitors. There also is evidence that thymulin stimulates cytokine release from certain types of lymphocytes (23).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Goya¹,

Reggiani²,

Vesenbeckh³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Integrity of the thymus during perinatal life is necessary for a proper maturation of the pituitarygonadal axis in mice and other mammalian species. Thus congenitally athymic (nude) female mice show significantly reduced levels of circulating gonadotropins, a fact that seems to be causally related to a number of reproductive derangements described in these mutants. Interestingly, a number of in vitro studies suggest that the thymic peptide thymulin may be involved in thymus-pituitary communication. To determine the consequences of low serum thymulin in otherwise normal animals, we induced short (8 days)-and long (33 days)-term thymulin deficiency in C57BL/6 mice by neonatally injecting (intraperitoneally) an anti-thymulin serum and assessed their circulating gonadotropin levels at puberty and thereafter. Control mice received an irrelevant antiserum. Gonadotropins were measured by radioimmunoassay and thymulin by bioassay. Both long-and short-term serum thymulin immunoneutralization resulted in a significant reduction in the serum levels of gonadotropins at 33 and 45 days of age. Subsequently, we injected (intramuscularly) an adenoviral vector harboring a synthetic DNA sequence (5′-ATGCAAGCCAAATCTCAAGGTGGATCCAACTAGTAG-3′) encoding a biologically active analog of thymulin, methionine-FTS, in newborn nude mice (which are thymulin deficient) and measured circulating gonadotropin levels when the animals reached 52 days of age. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels that typically emerges in these mutants after puberty. Our results indicate that thymulin plays a relevant physiological role in the thymuspituitary-gonadal axis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Thus thymulin has been shown to stimulate luteinizing hormone (LH) release from perifused rat pituitaries (29). Thymulin stimulated gonadotropin release from dispersed rat pituitary cells in a doserelated manner, an effect that declined with the age of the pituitary cell donors (5).…”

mentioning

confidence: 92%

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Goya¹,

Reggiani²,

Vesenbeckh³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…In thymulin deficient nude mice, morphometric analysis revealed that athymic nudes have reduced numbers of brain gonadotropin-releasing hormone (GnRH) neurons and pituitary gonadotropic cells, compared with heterozygotes, and neonatal thymulin gene therapy could prevent these changes (Reggiani et al 2009b, Martines et al 2011. Other studies suggested that thymulin stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) release from perfused rat pituitaries (Brown et al 2000, Hinojosa et al 2004. Moreover, thymulin could augment LH-mediated stimulation of androgen increases in vitro and in vivo in boar testis (Wise & Ford 1999).…”

Section: Introductionmentioning

confidence: 99%

Effects of GnRH immunization on the reproductive axis and thymulin

Su¹,

Sun²,

Zhou³

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

The bidirectional regulation of thymulin in the reproductive-endocrine function of the hypothalamic-pituitary-gonadal (HPG) axis of rats immunized against GnRH remains largely unclear. We explored the alterations in hormones in the HPG axis in immunized rats to dissect the repressive effect of immunization on thymulin, and to clarify the interrelation of reproductive hormones and thymulin in vivo. The results showed that, in the first 2 weeks of booster immunization, thymulin was repressed when reproductive hormones were severely reduced. The self-feedback regulation of thymulin was then stimulated in later immune stages: the rising circulating thymulin upregulated LH and FSH, including GnRH in the hypothalamus, although the levels of those hormones were still significantly lower than in the control groups. In astrocytes, thymulin produced a feedback effect in regulated GnRH neurons. However, in the arcuate nucleus (Arc) and the median eminence (ME), the mediator of astrocytes and other glial cells were also directly affected by reproductive hormones. Thus, in immunized rats, the expression of glial fibrillary acidic protein was distinctly stimulated in the Arc and ME. This study demonstrated that thymulin was downregulated by immunization against GnRH in early stage. Subsequently, the self-feedback regulation was provoked by low circulating thymulin. Thereafter, rising thymulin levels promoted pituitary gonadotropins levels, while acting directly on GnRH neurons, which was mediated by astrocytes in a region-dependent manner in the hypothalamus.

show abstract

“…There is a wealth of data, however, that correlate the anti-inflammatory actions of thymulin with various mechanisms. For example, it was shown that the growth hormone-releasing activity of thymulin is receptor-mediated and involves calcium (Ca 2+ ), cAMP and inositol phosphates [21]. Furthermore, thymulin has been reported to modulate intracellular cAMP in pathophysiologic conditions [19].…”

Section: American Journal Of Medical and Biological Researchmentioning

confidence: 99%

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Haddad¹,

Hanbali²

2013

AJMBR

View full text Add to dashboard Cite

The immunomodulatory activity of thymulin and related analogues in vivo is not well characterized in the CNS. We have previously provided evidence for an anti-inflammatory potential of thymulin in downregulating proinflammatory cytokines in a NF-B-dependent mechanism in vitro. Furthermore, we have shown that intracerebroventricular (ICV) treatment with thymulin in the hippocampus (HC) reduced the nuclear localization and activation of NF-B, an effect mediated by the IB-α/pIB-α pathway in vivo. ICV stereotaxic injection of endotoxin (ET) differentially upregulated the nuclear translocation /expression of NF-B 1 (p50), NF-B 2 (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the HC. Pretreatment with thymulin followed by ET exposure reduced the nuclear translocation of NF-B subunits. The anti-inflammatory effect of thymulin seems to be mediated via the IB- pathway since thymulin downregulated ET-induced phosphorylation of IB-. Stereotaxic pretreatment with synthetic peptide analogue of thymulin (PAT) reduced the nuclear translocation of NF-B subunits, an effect mediated by downregulating the phosphorylation of IB-. EMSA revealed dose-dependent inhibition of NF-B/DNA activation mediated by ICV ET. These results indicate that the anti-inflammatory effect of thymulin/PAT, mediated by IB-, is NF-B-dependent and involves the downregulation of the nuclear translocation of various NF-B subunits and their subcellular activation.

show abstract

Studies on the Gonadotropin-Releasing Activity of Thymulin: Changes With Age

Cited by 24 publications

References 30 publications

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Effects of GnRH immunization on the reproductive axis and thymulin

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Contact Info

Product

Resources

About

Studies on the Gonadotropin-Releasing Activity of Thymulin: Changes With Age

Cited by 24 publications

References 30 publications

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Effects of GnRH immunization on the reproductive axis and thymulin

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-&#954;B-Dependent and Involves the Downregulation of I&#954;B-&#945;

Contact Info

Product

Resources

About

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α