GHRP-2 Yields Physiologic Growth Hormone Release

GHRP-2 (growth hormone releasing peptide-2) is a synthetic version of ghrelin resembling Sermorelin,  that has been found to cause GH release. GHRP-2 is sometimes referred to as a second-generation GHRP as it was produced after initial research into molecules like GHRP-6. GHRP-2 is under investigation for use in growth hormone (GH) deficiency because it may produce a more physiologic effect than exogenous administration of recombinant growth hormone (rGH).

Drawbacks to Synthetic Growth Hormone

There are several problems with rGH. The first problem is due to the fact that GH can only be administered as boluses and often not in response to any particular physiologic state (i.e. eating, sleeping, etc.). GH release, under normal conditions, occurs in a pulsatile manner and never as a once-per-day bolus. It also fluctuates in response to sleep, exercise, food consumption, and several other factors.

The second problem with rGH is that it produces “square-wave” effects where levels rise and fall rapidly. Under normal circumstances, GH levels rise slowly to a peak and then fall again over time. The pattern looks more like a gentle wave, with peaks and valleys, rather than a box-like shape with steep on and off slopes.

The final problem with rGH injections is that they contain just one of the known variants of GH. Though the variants are similar in many ways, their subtle differences result in different activity levels in different tissues. The body produces these variants in different proportions in response to specific signals. With rGH injections, there is no way to control which GH variants are being injected and no way to alter those variants in response to physiologic signals.

Benefits of GHRP-2

GHRP-2 is a peptide, but it the peptide itself affects GH at an early stage in its production. This allows many normal physiologic controls to remain intact. In animal studies, GHRP-2 produced more normal pulsatile secretion of GH, more normal wave patterns, and almost no change in GH variant concentrations[1], [2]. Additionally, GHRP-2 has less impact on appetite than other GHRPs and so does not interfere with normal ghrelin signaling as much[3]. The result is that GHRP-2 more closely mimics normal mammalian physiology than recombinant GH or other GHRPs.



[1] L. T. Phung, H. Inoue, V. Nou, H. G. Lee, R. A. Vega, N. Matsunaga, S. Hidaka, H. Kuwayama, and H. Hidari, “The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine,” Domest. Anim. Endocrinol., vol. 18, no. 3, pp. 279-291, Apr. 2000.

[2] G. Baumann, “Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins,” Endocr. Rev., vol. 12, no. 4, pp. 424-449, Nov. 1991. Get full information at

[3] B. Laferrère, C. Abraham, C. D. Russell, and C. Y. Bowers, “Growth Hormone Releasing Peptide -2 (GHRP-2), like ghrelin, increases food intake in healthy men,” J. Clin. Endocrinol. Metab., vol. 90, no. 2, pp. 611-614, Feb. 2005.…


What Is Thyrotropin (TRH)?

Thyrotropin (also called thyrotropin-releasing hormone, TRH, and protirelin) is a naturally occurring hormone produced by the hypothalamus. It stimulates the anterior pituitary gland to release thyroid stimulating hormone (TSH) as well as prolactin. It is used clinically as a treatment for diseases of the spine as well as to treat disturbances of consciousness (e.g. following traumatic brain injury). It is currently being investigated by the United States military as a potential treatment for depression.

Thyrotropin Releasing Hormone Receptors

TRH interacts with cell-surface receptors (called TRH-Rs) to produce its effects much like Sermorelin. There are two TRH-Rs. TRH-R1 is found in the brain, primarily in the hippocampus and on the anterior pituitary. TRH-R2 is found in the hypothalamus, but is only present in rodents and may play a role in feedback1. TRH-R1 is often referred to only as TRHR when discussing human physiology.

The function of TRH-R1 is identical in rodents and humans. That makes it possible to study the effects of TRH binding to the receptor in various regions of the brain. The effects of TRH depend not on the receptor it binds to, but depend upon where the receptor is located, an interesting and somewhat unique physiologic mechanism.

TRH and the Anterior Pituitary

TRH binding to TRHR in the anterior pituitary leads to the release of prolactin as well as the release of TSH. TSH then goes on to bind to receptors on the thyroid gland and cause release of thyroid hormones T3 and T4. Only T3 is active in causing further effects. T4, though inactive, is slowly metabolized to T3. Effects of T3 include

.   Increasing cardiac output,

.   Increasing heart rate,

.   Increasing breathing rate

.   Increasing basal metabolic rate,

.   Increasing sympathetic activity,

.   Improving neuron survival and differentiation, and

.   Increasing metabolism of proteins and carbohydrates.

Clinically, synthetic thyroid hormone (called Synthroid) is used directly to treat hypothyroidism and very little else. Elevations in thyroid hormones can lead to increased fat loss and help fight obesity, but side effects have prohibited such use for synthetic thyroid hormone.

Prolactin is often associated with milk production and while that is one of its primary functions, prolactin has more than 300 different actions on the human body. In fact, it is secreted in response to eating, mating, ovulation, and nursing. Some studies have even shown that prolactin plays a major role in animal pair-bond formation in romantic relationships. Other functions of prolactin include-

.   Water/salt balance,

.   Immune system regulation,

.   Cell cycle regulation (it acts as a growth factor),

.   Sexual gratification,

.   Myelin formation,

.   Blood clotting,

.   Blood cell formation, and

.   Blood vessel development.


TRH and the Hippocampus

The hippocampus is a region of the brain found on the floor of each lateral ventricle in each cerebral hemisphere. Research suggests that it plays active roles in emotion, memory, and the function of the autonomic nervous system. It is one of the first regions in the brain to suffer damage in Alzheimer’s disease.

That TRHRs are found in the hippocampus is unsurprising because TRH has long been known to have anti-depressant and anti-suicidal properties. It has also been shown to have anti-aging properties in mice, which include improved kidney function, improved gonadal function, improved arousal (wakefulness) and improved memory2 .Learn more detailed updates at

Recently TRHRs have been found in the cerebellum, the part of the brain responsible for balance and coordination. Studies in rats have demonstrated an improvement in ataxic (uncoordinated) gate after administration of both TRH and TRH analogs3 .


TRH is a natural hormone with vast and diverse functions that result from the wide and varied distribution of TRH receptors. Administration of TRH, while stimulating thyroid hormone release, is not associated with the dramatic side effects found with direct thyroid hormone administration. This is because TRH is subject to feedback mechanisms at both the anterior pituitary and (indirectly) at the thyroid gland that attenuate its effects. Its effects in the hippocampus and cerebellum do not appear to be attenuated, however, and thus TRH is under active investigation as a potential treatment for depression, memory problems, and ataxic gate.


  1. Sun, Y., Lu, X. & Gershengorn, M. C. Thyrotropin-releasing hormone receptors — similarities and differences. J. Mol. Endocrinol.30, 87-97 (2003).
  1. Pierpaoli, W. Aging-reversing properties of thyrotropin-releasing hormone. Curr. Aging Sci.6, 92-98 (2013).
  1. Shibusawa, N., Hashimoto, K. & Yamada, M. Thyrotropin-releasing hormone (TRH) in the cerebellum. Cerebellum Lond. Engl.7, 84-95 (2008).

What Is PT-141 (Bremelanotide)?

Bremelanotide was formerly known as PT-141 and is a peptide drug originally developed by Palatin Technologies. Bremelanotide has been put forth as a treatment for everything from hemorrhagic shock to female sexual dysfunction. It derives its effects through stimulation of melanocortin receptors and is a derivative of the well-known drug melanotan II (melanotan 2). Bremelanotide is considered more tolerable than melanotan 2 and is known to have fewer side effects like sweating and yawning1,2.

Bremelanotide Properties

Bremelanotide (PT-141) is a member of the large class of molecules known as melanocortins, molecules that exert effects through binding to several melanocortin receptors (MCRs). Which receptors a particular melanocortin binds to determines the properties of that agent. Bremelanotide primarily binds to MCR(4) and thus influences male and female sexual function.

In truth, bremelanotide, much like the Sermorelin peptide, binds to all of the MCRs, with the exception of MCR(2), though with lower affinity than to MCR(1) and MCR(4). This means it avoids the unpleasant side effects associated with stimulating the adrenal glands. It plays a role in reducing inflammation and in reducing ischemia.


Bremelanotide (PT-141) was originally developed as a nasal spray and was undergoing clinical testing in the early part of the twenty-first century as a potential treatment for female sexual dysfunction. Unfortunately, it was found to produce high blood pressure and the trials were halted. Palatin reformulated the drug to be injected and the high blood pressure side effect was reduced. Clinical trials resumed, but the FDA expressed concern and the development of Bremelanotide was discontinued in 2008.


In 2009, Palatin began to develop a slightly modified version of Bremelanotide, called PL-6983, as a treatment for hemorrhagic shock3. Its actions on the MCR(1) and MCR(4) receptors mean the drug reduces ischemia and thus protects tissues derived of adequate blood supply. Once again, this drug was administered via injection through the subcutaneous route. It was found to have no hypertensive effects and has completed phase IIb human trials with very positive results. This drug will likely be used off-label in the future as a treatment for female sexual dysfunction providing it receives FDA approval as a treatment for hemorrhagic shock, continue reading this at


  1. Safarinejad, M. R. & Hosseini, S. Y. Salvage of Sildenafil Failures With Bremelanotide: A Randomized, Double-Blind, Placebo Controlled Study. J. Urol.179, 1066-1071 (2008).
  1. Safarinejad, M. R. Evaluation of the Safety and Efficacy of Bremelanotide, a Melanocortin Receptor Agonist, in Female Subjects with Arousal Disorder: A Double-Blind Placebo-Controlled, Fixed Dose, Randomized Study. J. Sex. Med.5, 887-897 (2008).
  1. Rössler, A.-S. et al. The melanocortin agonist, melanotan II, enhances proceptive sexual behaviors in the female rat. Pharmacol. Biochem. Behav.85, 514-521 (2006).