Author: Richard Blanchard

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Heparin binding EGF is part of the EGF mitogen group that includes other chemicals including amphiregulin, growth factor alpha, vaccinia growth factor, and rat schwanoma-derived growth factor. There are also various ligands from the erbB2/HER2 or neu receptor family within this group. A great deal of these trans-membranes precursors are considered to be ‘biologically active’, which means that HB EGF plays an active role in juxtacrine stimulation within adjacent cells.

Research has revealed a variety of reactions to HB EGF in animal bodies. It is believed that this peptide is expressed in cultured human macrophages that will impact the macrophage-mediated cellular proliferation within this body.

It also appears as though visceral obesity within the metabolic syndrome may increase fatty acid output, when exposed to EGF growth factor. This has been shown regularly in the adipose tissue of laboratory mice. It has been noted that myeloid leukemia cells have been may react to HB EGF by expressing diphtheria toxin receptors.

Inhibiting Cardiac Hypertrophy

GPCR receptor antagonists have been strongly documented as inducing cardiac hypertrophy though new research indicates that shedding HB EGF may result the metalloporoteinase activation.

• This will in turn transactivate the epidermal growth factor receptor which occurs during cardiac hypertrophy.
• An inhibitor of this HB EGF shedding known as KB-R7785 can be used to block this signaling to prevent cardiac hypertrophy. Metalloprotease 12 can be cloned to create a specific enzyme that will cause HB-EGF to shed within the heart.
• Metalloprotease may cause abrogated signaling of HB EGF while KB-R7785 may inhibit this shedding as well as annenuated hypertrophic changes.

This data suggests that mice that have cardiac hypertrophy may be assisted by metalloprotease in managing their condition. It also suggests that HB EGF shedding may be an encouraging therapeutic strategy for the cardiac hypertrophy symptoms these animals have expressed.

Potential to Restore Neurogenesis in the Hippocampus

It is believed that neurogenesis helps to contribute to adult brain function, though this declines with age.

• Research indicates that applying growth factors to the brain tissue may enhance adult neurogenesis though the age where this response would be ideal is unknown.
• To test this theory HB EGF was applied to adult mice at a variety of ages and the responses of the brain as well as the quality of the brain tissue was regularly tested.

Research demonstrated that the aged brains of the mice would retain the capacity to respond to exogenerous growth factor along with increased neurogenesis. This implies that HB EGF may have therapeutic potential in enhancing the brain’s ability to ward off age related neurological disorders.

Introducing HB EGF to metalloprotease inhibitors and the abrogation of EGF receptors and their kinase activity within selective antisense oligonucleotides and pharmacological inhibitors which can help to protect the cells against Ang II mediated cardiac hypertrophy.

This can be demonstrated by introducing lysophosphatidic acid induced ectodomain by means of shedding the HB EGF growth like factor. This is considered critical to the formation of the tumors that make up an ovarian cancer infection, which has become a prime candidate for research.

Sources:

http://www.nature.com/nm/journal/v8/n1/abs/nm0102-35.html
http://onlinelibrary.wiley.com/doi/10.1046/j.1474-9728.2003.00046.x/full

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Gonadorelin acetate may be produced under a variety of names, based on the country where the synthesized version of this peptide was produced. Potential branding for this peptide include lutenizing hormone-releasing factor dihydrochloride, like lutenizing hormone-releasing hormone,.

This hormone is used by an animal’s body as a diagnostic aid that assists with hypothalamic-pituitary axis function. Some studies have also looked into the potential use of the synthesized version of this peptide as an infertility therapy agent.

When produced by an animal’s body gonadorelin acetate acts as a natural gonadotropin releasing hormone (GnRH) which is primarily used as a means of synthesizing and releasing luteinizing hormone throughout the body from the anterior pituitary gland. This chemical can also act as a follicle stimulating hormone by increasing production of this chemical, though research has indicated that this behavior occurs to a much lesser degree.

Research often centers around applying this chemical in prepubertal female test subjects as a means to control or eradicated gonadal function disorders that may require an additional LH or FSH response from the body.

Responses to Gonadorelin in Holstein Heifers

LH and FSH concentrations in heifers were monitored after intramuscular applications of fertirelin acetate and GnRH products including gonadorelin acetate.

• Each heifer was exposed to nine applications of each chemical for 8-16 day cycles. Groups were exposed to buserelin, gonadorelin acetate or fertirelin acetate.
• After these applications blood samples were drawn 1-8 hours later to log the responses to these chemicals and the different reactions between them.
• After plotting this data it was determined that a plateau could be reached applying fertirelin acetate more quickly than the other chemical bodies.

In general it was found that fertirelin acetate could be between 2.5-10 times stronger than gonadorelin while buserelin is around 10-0 times more potent than these chemicals in facilitating FSH or LH release.

Pulsatile Delivery Systems

Researchers are focusing a great deal on providing a delivery system for peptides, drugs and hormones through a reproductive or endocrine delivery system.

• The idea behind this interest is that these applications would be able to stimulate pulsatile releases of natural hormones in animals to enhance fertility.
• The luterpulse system has been studied as a means of stimulating GnRH production in the hypothalamus. This system relies on mechanical pumps that would better supply these chemicals on a given schedule.

Currently this system is being tested with temperature regulated chemical releases using sonophoresis, iontophoresis or mechanically regulated chemical releases. Gonadorelin acetate is one of the primary chemicals being tested with this method as it has been shown to be an effective stimulator of GnRH.

Gonadorelin acetate that is prepared for research settings is designed with a rapid metabolism as compared to other biologically inactive peptide fragments. The initial half-life of this chemical is 2-10 minute with a terminal half-life of 10-40 minutes. The duration of the action of gonadorelin acetate is 3-5 hours once applied. It is eliminated from the body via inactive metabolites or renal excretion which may vary based on the application.

Sources:

http://www.sciencedirect.com/science/article/pii/0093691X9090579I
http://www.sciencedirect.com/science/article/pii/0169409X91900317

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Ceterorelix acetate refers to a gondatropin releasing hormone antagonist. This is a synthetic decapeptide that is regularly researched for its role in combating hormone sensitive cancers, such as breast or prostate cancers, as well as its roles in some gynecological disorders in women. Cetrorelix acetate may also be researched for its potential in inhibiting surges of luteinizing hormones by blocking the GnRH from the pituitary gland. This peptide is capable of suppressing an animal’s production of FSH and LH for this purpose.

Cetrorelix acetate is commonly applied via injection to animal test subjects in 3mg applications every four days or a .25mg application when it is being administered to test subjects along with regular applications of hCG. These application sizes may vary based on the age, sexual development and species of the test subject in question.

It may be necessary to closely monitor male animal test subjects that are exposed to this chemical as it has been shown to alter the concentrations of High Density Lipoproteins in animals that were regularly exposed to this chemical which may alter the effects and results of a given study.

Systematic Delivery in Anesthetized Rats

Reactions and pulmonary absorption of cetrorelix acetate was followed in rats using a method of non-surgical intratracheal instillation.

Four groups of rats including seven rats each were provided with varying concentrations of cetrorelix along with two control groups containing ten and nine rats respectively.

After the chemical was administered the resistance time was followed using plasma samples which suggested that the chemical was quickly absorbed by the rats’ bodies.

Studies using this method have indicated that intratracheal instillation of cetrorelix acetate using this method can be adopted to provide a non-surgical cannulation that can provide reliable results for researchers. This also helps to indicate that large amounts of active cetrorelix acetate in an animal can be absorbed by the lungs.

Acting as a Potent Antagonist of LH-RH

Hormone suppressing effects and antitumour of lutenising hormone releasing hormone antagonist Cetrorelix was measured using the investigative model that induced DMBA within mammary carcinoma of male and female rats.

Single applications beginning with a high amount of the chemical moving down to maintenance sized applications were applied to each group.

The stability of each molecule that was affected by the degrading enzymes indicated that this poorly soluble pamoate salt was inadequate for facilitating sustained release of active compounds.

These salts did produce a suppression that prolonged testosterone levels and tumor growth. This allowed researchers to conclude that cetroroelix may be a useful LH-RH antagonist that could be developed more fully to address hormone dependent diseases.

Regular and high applications of cetrorelix in animal test subjects have also been found to cause severe renal impairment in some test subjects. This is particularly found in female test subjects which are advanced in age, past the point of a natural menopause.

There is also a very high record of allergic reactions of cetrorelix in a variety of types of animal test subjects, so any animals exposed to this peptide should be monitored with care.

Sources:

http://www.sciencedirect.com/science/article/pii/S0928098799000676
http://www.sciencedirect.com/science/article/pii/0959804996001384

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