Mgf (Mechano Growth Factor)

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Mgf refers to mechano growth factor, a hormone that is produced in muscle tissue of animals when the muscles are trained. This chemical is considered to be an isoform of IGF-1. This spliced variant shares the mature region with IGF-1 but has a different E domain. The C-terminal sequence between these two chemicals shows a distinct variant that allows researchers to differentiate between the two bodies.

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Mgf is associated with promoting healing in the muscles of animal subjects after they have been damaged. In a natural setting, the chemical can stimulate the stem and satellite cells in addition to the necessary anabolic processes to promote the growth of new tissue or muscle fibers by tissues that were not damaged.

It is believed that mgf and IGF-1 are central to the regrowth of muscle and the primary anabolic mechanism used to create new tissue.

Inability to Naturally Express Mgf Due to Mechanical Overload

Studies are investigating the response of IGF-1 signals and the capacity of skeletal muscle in an animal subject to react to the mechanical overload of this chemical by using synergistic muscle ablation.

  • Overloading the soleus and plantaris caused a significant hypertrophy response as well as activation of the satellite cells. This response was more noticeable in younger rats.
  • To splice variants of IGF-1 were found to be regulated differentially by RNA levels.

Significant changes that could be associated with an inability of older muscles in the subject’s body to manage mechanical overload resulted in a lower expression of the splice variant applied in that area as well as the machano growth factor.

This also created a failure for these muscles to un-regulate the IGF-1 receptors, mRNA and MyoD.

Expression of Actions in Rat Cardiomyocytes

A study worked to investigate the expression patterns of IGF-1 gene in rat myocardium between one hour and eight weeks after an induced myocardial infarction that was caused by coronary artery ligation at left anterior.

  • Mgf-E and IGF-1 actions were characterized as well as the respective signals to H9C2 myocardial-like cells that were in vitro.
  • Throughout the study period mgf and IGF-1Ea expressions increased significantly at the translational and transcriptional levels, particularly during the post-infarction period at 4-8 weeks.
  • The measurements of IGF-1 serum levels in the rats decreased in the 24 hour to one week period, but then did not change in the later portions of the experiment when they were compared with sham-operated control rats.
  • The specific anti-IGF-1r neutralizing antibodies during this period failed to block synthetic mgf-E particles and did not activate the Akt phosphorylation, but groups exposed to ERK1/2 did.

The summary of this data leads researchers to believe that the expression of IGF-1 during myocardial repair is essential. It also leads researchers to believe that the presence of synthetic mgf-E peptides could be mediated using an IGF-1R independent pathway, as was expressed in the in-vitro experiments focusing on the rat myocardial cells.

Continuing research is necessary to determine how mgf varies from other naturally occurring peptides as well as how to naturally stimulate this chemical in animals.

Sources:

http://www.sciencedirect.com/science/article/pii/S0014579301028253

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656994/

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GnRH (Gonadotropin-Releasing Hormone)

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GNRHGnRH refers to the gonadotropin-releasing hormone which may also be known as the luteinizing hormone releasing hormone or LHRH. This is a trophic peptide hormone that is used as a follicle stimulator as well as a lutenizing hormone within the anterior pituitary.

In a natural setting, GnRH is synthesized and then released from the neurons of the hypothalamus. When experimenting with mammal subjects, such as rhesus monkeys, the product is synthesized from the 92-amino acid known as preprohoromne that is located in the preoptic anterior hypothalamus.

Study Related to Ovulation

Studies in He de France and Suffolk focused on how GnRH was secreted prior to ovulation in ewe.

  • Previous studies established that physiological estradiol is accompanied by a sustained and significant surge of GnRH. However, these studies did not determine the consistency of this effect during a preovulatory LH surge.
  • To better understand these effects, a group of ewe were gathered during their preovulatory period for further study. Jugular blood samples were taken in intervals throughout a 48 hour period. These ewes were examined during the follicular or luteal phases.
  • Results showed that during the follicular phase, there was a significant increase of GnRH secretions, particularly before the surge of LH. The surges of GnRH were nearly 40x greater and lasted significantly longer than the LH surges. No ewes showed evidence of a GnRH surge during the LH surge or in the blood samples collected in the postmortem inspection of the pituitary portal vessels.
  • Additionally, the pulse frequency during the GnRH surge was larger than the surge during the luteal phase. During the follicular phase the pulse frequency of GnRH increased again while the amplitude decreased as the surge continued to approach.

The results of this study help to demonstrate the GnRH secretions that occur prior to ovulation in the ewe. These secretions are dynamic in nature, starting off as slow pulses throughout the luteal phase and increasing in frequency throughout the follicular phase before culminating in a surge of GnRH.

Evidence for Pulsatile Release of GnRH

GnRH levels in rhesus monkeys were measured throughout a study to better determine the release patterns of this chemical in a natural setting.

  • The portal blood from the hypothalamic-pituitary stalk was collected from female rhesus monkeys by cutting at the diaphragm sellae. This blood was continuously obtained for half hour intervals throughout the nine hour period with a constant exfusion pump.
  • The GnRH fluctuations in the blood increased most prominently in those that were ovariectomized with peaks occurring every 1-3 hours.
  • Three monkeys were administered estradiol at 1000 ng via IV to determine if this would have an impact on the decreasing the GnRH levels in these animals. Over the next two hours, there would be no decrease in the GnRH levels present in the monkeys.

The results of this study fail to provide any direct evidence for hypothalamic meditation within the pituitary LH pulsatile release. Additional study is required to better understand the workings of this cycle in primate subjects.

The ongoing study of the natural effects of GnRH will better assist scientists with creating a proper synthetic solution of this chemical.

Sources:

http://endo.endojournals.org/content/99/1/243.short

http://endo.endojournals.org/content/129/3/1175.short

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PT141 (Bremelanotide) 10mg Vials

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pt 141 onlinePT141 is a melanocortin agent that can be used to stimulate the central nervous system in animals without having to directly affect the vascular system. Researchers hope to better determine proper levels of administration for this chemical so it can one day replace products such as Cialis, Viagra or other phosphodiesterase-5 inhibitors (PDE-5 inhibitors) that are known to exhibit potentially dangerous side effects.

Unlike PDE-5 inhibitors, PT141 has not yet been approved for use in men or women. Ongoing studies are comparing the effects of both classes of chemicals on a variety of animal subjects to better understand their effects on different organ and tissue symptoms. There is not yet an approved dosing that is considered safe for use.

Potential Use Against Sexual Dysfunction

Synthetic PT141 acts as an antagoinist of melanocortin receptors which are found in the central nervous system such as MC3R and MC4R.

  • Studies indicate that administering PT141 in rats and other nonhuman primates can cause penile erections.
  • Systematically administering PT141 to these rats has been found to activate the neurons within the hypothalamus. This is shown by increases in c-Fos immunoreactivity in the subjects.
  • Other neurons in this region of the central nervous system were found to take up the pseudorabies virus when it was injected into the animal’s corpus cavernosum in the penis.

When PT141 was administered to male animals that suffered from erectile dysfunction but otherwise exhibited normal health, erectile activity would improve. The increase in erectile activity was directly linked to a dependence on the application of PT141 and the given levels of the application in the given test subject. While these results are initial and somewhat limiting in nature, they imply that PT141 may have potential in therapeutic treatment of erectile disorders in the future.

Effects on Sexual Solicitation in Rats

Because female sexual dysfunction can be caused by a variety of physiological, personal and interpersonal triggers there are no pharmaceutical agents that can assist with this disorder, but research indicates that PT141 may have future use in this category.

  • In a recent study, PT141 was the focus of a study that addressed the reactions of this peptide in female rats.
  • PT141 binds to the central melanocortin receptors which will in turn selectively stimulate the solicitational behaviors exhibited by the female rat. It was revealed that these stimulations occurred independently of pacing, lordosis or other sexual behaviors.
  • The application of this chemical did not result in generalized motor activation or the rat’s perception of the sexual reward.

This very selective effect on sexual behavior of female rats has not been reported in other similar studies. This implies that the central melanocortin systems may be important in the regulation of sexual desire in females and PT141 may be able to stimulate this area to help better manage disorders involving sexual desire.

Studies that study the varying effects of PT141 on male and female animal subjects are ongoing to help scientists better understand how this chemical affects natural hormones. Ongoing studies are also focusing on the potential side effects of these artificial chemicals may have when interacting with hormones and bodily produced chemicals within a natural setting.

Sources:

http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2003.tb03167.x/abstract

http://www.pnas.org/content/101/27/10201.short

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