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GnRH 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 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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GHRP2 stimulates the release of an endogeneous hormones within the somatotropes of the anterior pituitary in the animal body. Specifically, GHRP2 will increase the number of somatotropes by limiting the amount of somatostatin present while standard GHRH increases the amplitude at which the pituitary cells pulse.

Unlike ghrelin, GHRP2 is not used to increase appetite, but it may have secondary actions that will impact the hypothalamic neurons. These effects last for approximately an hour after the initial application. This mimics the natural application of GH which consists of an eight hour circulation period.

Effects on Secretions in Ovine and Rats

Previous studies investigated the actions of GHRP6 and GHRP2 on GH releases in the rat and pituitary cells, and a follow up study focused on increasing these concentrations to create GH dependency to better understand potential dosing restrictions, should this chemical be used in therapeutic sessions in the future.

• GHRP2, GHRP6 and GRF were applied in increasing concentrations to partially purified sheep somatrophs to cause a release of hormones in a dependent manner. GHRP6 was not found to increase the cAMP levels. Mixtures of GRF and GHRP2 were found to increase and cAMP levels, but a combination of GHRP2 and GHRP6 did not.

• When the cells were pretreated with an adenylyl cyclase inhibitor, they did not see a cAMP increase. This antagonist did not prevent cAMP reactions when GHRP6 was applied.

• When the antagonist was applied to the receptor, the GHRP2 and GRF combination did not increase the cAMP rates when GRF, GHRP2 or GHRP6 were applied.

These results indicate that GHRP2 can affect the ovine pituitary somatotroph to increase cAMP concentrations in a similar way that GRF does. However, GHRP2, GHRP6 or GRF all act on different receptors which would be why GHRP6 did not have an effect cAMP levels on the rat pituitary cell cultures.

Anti-Inflammatory Effects in Arthritic Rats

This study focused on the proper administration of GHRP2 on arthritic rats.

• Rats were injected with Freund’s adjuvant and then given daily exposures to GHRP2 or ghrelin fifteen days later.

• Those exposed to the ghrelin serum saw a decrease in their lepin concentrations, while those given GHRP2 saw ameliorated external symptoms of their arthritis and a decrease in their paw volume.

• GHRP2 also decreased IL-6 levels when they had originally been increased by the arthritis symptoms.

The results of this study help to show that GHRP2 may have use in managing IL-6 levels affected by arthritis. This further implies that GHRP2 may have anti-inflammatory properties as the chemical appeared to have a positive effect on managing the ghrelin receptors and immune cells that were affected by the disease.

The comparison of GHRP2 to similar chemicals in a natural setting is ongoing to assist researchers in evaluating the similarities in composition so the study of this chemical can be expanded to additional animals.

Sources:

http://joe.endocrinology-journals.org/content/148/2/197.short

http://ajpendo.physiology.org/content/288/3/E486.short

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