Oxytocin: An Aged Muscle Repair Assistant Agent?

Thesis 2014: Oxytocin , is FDA approved. Previously thought of a hormone for lactation and social behaviors  is advancing on a front driven by the realization that OCT receptors are throughout the body. Current studies are

1. osteopenia, obesity feedback via hypothalamus stimulation via OCT injection
2. thymus and t cell immunity axis
3. muscle repair via stem cell stimulation
4. 1 rat experiment- appears over expression of liver enzyme of oxytocinase is responsible for OCT destruction.

Muscle repair via stem cell stimulation

A blog intro- http://blogs.discovermagazine.com/science-sushi/2014/06/27/new-study-shows-muscles-love-oxytocin/#.U7Jh-EBCBow

 

Careful here - "When the team looked closely at what was happening in the regenerating muscle cells, they found that oxytocin turns on a well-known cellular cascade that triggers growth and proliferation: the MAPK/ERK signaling pathway.  "

 

 

The Starting point

 

 http://www.ncbi.nlm.nih.gov/pubmed/24915299   Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration.

Elabd C¹, Cousin W¹, Upadhyayula P², Chen RY², Chooljian MS², Li J², Kung S², Jiang KP², Conboy IM².

Author information

• ¹1] Department of Bioengineering, Stem Cell Center, QB3 Institute, UC Berkeley, Berkeley, California

Abstract

 

The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation; however, systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin-a hormone best known for its role in lactation, parturition and social behaviours-is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signalling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation through activation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle but instead leads to premature sarcopenia. Considering that oxytocin is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle ageing.

Rate : 1microgram of OCT per gram of mouse ie 1miligram per kg of mouse ie 80mg per 80 kg mouse. Roughly equals  2mg per 80kg human using surface area multiplier.

Low Oxytocin,  Liver and Oxytocinase Activity

from this paper J Endocrinol. 2014 Feb 10;220(3):333-43.

Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue.

 http://www.ncbi.nlm.nih.gov/pubmed/24389591

 "Obese Zucker rats displayed a marked reduction in plasma oxytocin levels. Elevated liver and adipose tissue oxytocinase activity was noticed in obese Zucker rats. Hypothalamic oxytocin gene expression was not altered by the obese phenotype. OXTR mRNA and protein levels were upregulated in the adipose tissue of obese animals in contrast to the reduced OXTR protein levels in skeletal muscle. Our results show that obesity is associated with reduced plasma oxytocin due to increased peptide degradation by liver and adipose tissue rather than changes in hormone synthesis. This study highlights the importance of the oxytocin system in the pathogenesis of obesity and suggests oxytocinase inhibition as a candidate approach in the therapy of obesity."


Osteopenia and Obesity

Endocrinology. 2014 Apr;155(4):1340-52.

Oxytocin reverses ovariectomy-induced osteopenia and body fat gain.

http://www.ncbi.nlm.nih.gov/pubmed/24506069
Thus, OT constitutes an effective strategy for targeting osteopenia, overweight, and fat mass redistribution without any detrimental effects in a mouse model mimicking the menopause

Treatment of Obesity and Diabetes Using Oxytocin or Analogs in Patients and Mouse Models

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658979/

 Here, based on a randomized pilot clinical trial, we report that intranasal oxytocin administration over an 8-week period led to effective reduction of obesity and reversal of related prediabetic changes in patients.

Human data

 http://iv.iiarjournals.org/content/24/2/157.full.pdf

 

Abstract.

Background: It has been shown that the

neurohypophyseal peptide oxytocin is present in the human

thymus and in vitro it can mimic interleukin (IL)-2 action in

the induction of interferon-γ production.he present results support the hypothesis that neuropeptides

may act as a link in the network between the immune and the

neuroendocrine systems
 http://www.ncbi.nlm.nih.gov/pubmed/19479077

 PLoS One. 2009 May 22;4(5):e5668. doi: 10.1371/journal.pone.0005668.

Impact of growth hormone (GH) deficiency and GH replacement upon thymus function in adult patients.

Morrhaye G¹, Kermani H, Legros JJ, Baron F, Beguin Y, Moutschen M, Cheynier R, Martens HJ, Geenen V.

Author information

Abstract

BACKGROUND:

Despite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels.

METHODOLOGY/PRINCIPAL FINDINGS:

Twenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/beta TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/beta TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/beta TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal.

CONCLUSIONS:

In patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.

TRIAL REGISTRATION:

ClinicalTrials.gov NTC00601419.