Overview
GHRP-2, also known by its pharmaceutical name Pralmorelin, is a synthetic hexapeptide belonging to the growth hormone secretagogue (GHS) family of peptides. It was designed to mimic the action of ghrelin, a naturally occurring hormone, by stimulating the release of growth hormone from the pituitary gland through a specific receptor pathway. With a molecular weight of approximately 818 Da and the CAS number 158861-67-7, GHRP-2 is one of the more well-characterized peptides in its class and has been the subject of published scientific studies exploring hypothalamic-pituitary function and related endocrine signaling. Researchers have used GHRP-2 as a investigative tool to study how the hypothalamic-pituitary axis responds under various physiological and pathological conditions, including work examining ACTH deficiency and pituitary cell function. GHRP-2 is intended strictly for laboratory and research purposes and is not approved for human use or consumption.
Research & Bioactivity
GHRP-2 (Growth Hormone-Releasing Peptide-2) is a synthetic hexapeptide that researchers have studied extensively in relation to the hypothalamic-pituitary axis, particularly its role in stimulating growth hormone secretion. Studies have examined its use as a provocative agent in growth hormone testing, including investigations into peak GH response levels in adolescent populations, where it has been noted to produce robust secretory responses compared to other stimulation methods. Research has also investigated GHRP-2 in the context of anterior pituitary function assessment, with clinical studies utilizing it as a diagnostic tool to evaluate hypothalamic-pituitary responses in conditions involving endocrine dysfunction. Beyond its endocrine applications, animal model research has explored GHRP-2 in the context of tissue repair, with one rat rotator cuff tear model examining its potential association with macrophage polarization and tendon-bone healing properties at both the histological and biomechanical levels. In vitro components of that same research used molecular techniques including Western blot and immunofluorescence staining to investigate effects on M1 macrophage production. Collectively, published research has positioned GHRP-2 as a subject of interest across neuroendocrinology, diagnostic endocrinology, and musculoskeletal biology, with studies conducted in both animal models and human clinical settings.
Published Research
Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone.
Otsuka Y, Soejima Y, Nakano Y, Suyama A, Takase R, et al. — 2026
Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic-pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (-0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements.
One Case of Sudden Isolated Adrenocorticotropic Hormone (ACTH) Deficiency Diagnosed Based on Repeated Hypoglycemic Attacks.
Sato T — 2025
Our patient is a 28-year-old male who was being treated by a local doctor for Hashimoto's thyroiditis. Four days prior to admission, nausea and diarrhea appeared, and it gradually became difficult for him to eat. The night before admission, his level of consciousness decreased (Japan Coma Scale (JCS) II-20), and he was rushed to the hospital. His other vital signs were stable. After completing a detailed examination, the cause was diagnosed as hypoglycemia with a blood glucose level of 21 mg/dl. After the administration of glucose, he regained consciousness and became alert, allowing him to return home, with the expectation that he would return to the hospital for a follow-up visit at a later date. However, an altered consciousness (JCS I-3) appeared again the next morning. Similar to the previous day, the cause of the altered consciousness was determined to be hypoglycemia. After making a detailed inpatient examination, his early morning fasting serum cortisol level was found to be less than 0.1 μg/dL, and his blood adrenocorticotropic hormone (ACTH) was 3.1 pg/mL, thus indicating decreases in both. After performing rapid ACTH testing, almost no increase in the serum cortisol levels was observed after 30 minutes and 60 minutes following ACTH administration, thus suggesting the presence of adrenal insufficiency. According to a contrast-enhanced CT of the abdomen, atrophy of both adrenal glands was observed; however, there was no macroadenoma or the like according to the contrast-enhanced MRI of the brain. Based on the results of the ACTH continuous load test, triple anterior pituitary stimulation test with corticotropin-releasing hormone (CRH) thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH),growth hormone-releasing peptide-2 (GHRP-2) load test, and insulin hypoglycemic load test, no abnormalities were found in his pituitary functions other than ACTH-cortisol, and no history of trauma or adenoma lesions, leading to a diagnosis of a sudden isolated ACTH deficiency. The patient has remained stable with no hypoglycemic episodes since treatment with hydrocortisone was initiated. Based on the fact that isolated ACTH deficiency is often associated with a complication of autoimmune endocrine disease, an autoimmune mechanism has been speculated. Although the disease is rare, it is an important disease that affects the quality of life (QOL) of patients, and it should therefore be considered when making a differential diagnosis.
Benchmark for Setting ACTH Cell Dosage in Clinical Regenerative Medicine for Post-Operative Hypopituitarism.
Kondo T, Suga H, Takeuchi K, Fuse Y, Sato Y, et al. — 2025
BACKGROUND/OBJECTIVES: Our objective is to develop hormone-producing pituitary cells that can function in the same manner as the human body and provide more effective treatments than current hormone replacement therapy. We have already established a technique for generating hypothalamic-pituitary organoids using feeder-free human pluripotent stem cells (hPSCs) and demonstrated their effectiveness in vivo through transplantation into hypopituitary mouse models. To prospectively determine the upper limit of transplanting adenohypophyseal cells into humans, we investigated the human maximum secretion capacity of adrenocorticotropic hormone (ACTH) and growth hormone (GH). METHODS: We analyzed data from 28 patients with pituitary adenomas, among whom 16 evinced no abnormality of ACTH secretion and 12 showed no GH secretion on corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone-2 (GHRP-2) stimulation testing. RESULTS: The average ACTH peak value after CRH stimulation tests was 97.2 pg/mL, and the average GH peak value after GHRP-2 stimulation tests was 25.1 ng/mL. CONCLUSIONS: These data will likely serve as benchmarks of ACTH and GH secretion when transplanting cultured cells into humans.
Growth Hormone-Releasing Peptide 2 May Be Associated With Decreased M1 Macrophage Production and Increased Histologic and Biomechanical Tendon-Bone Healing Properties in a Rat Rotator Cuff Tear Model.
Li Y, Yao L, Zhang C, Li T, Wang D, et al. — 2025
PURPOSE: To explore the potential of growth hormone-releasing peptide 2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear (RCT) model. METHODS: The impact of GHRP-2 on M1 macrophage polarization in vitro was determined using real-time polymerase chain reaction, Western blot, and immunofluorescence staining. GHRP-2 was then applied in a rat RCT model, and the healing of the tendon-bone interface was systemically evaluated by histologic staining, radiologic assessments, gait analysis, and biomechanical tests. M1 macrophage polarization at the tendon-bone interface was assessed by immunofluorescence staining. RESULTS: GHRP-2 was found to reduce the expression of Cd86, Nos2, and tnfa (all P < .01), suggesting inhibited M1 macrophage polarization in vitro. The in vivo experiments showed that the proportion of M1 macrophages was reduced both 2 and 4 weeks after surgery (P < .01), and the number of M1 was reduced 4 weeks after surgery (P < .01) at the tendon-bone interface. The in vivo experiments also showed that histologic scores and bone mineral density were increased by GHRP-2 at 8 weeks postsurgery (P < .01), suggesting improved healing of the tendon-bone interface. Furthermore, the GHRP-2 group showed a better biomechanical property at both 4 and 8 weeks postsurgery, including maximal failure load, stiffness, and tension (all P < .01), and better gait parameters at 8 weeks postsurgery, including mean area of the left front foot and mean intensity of the right front foot (all P < .05). CONCLUSIONS: GHRP-2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in a rat RCT model. CLINICAL RELEVANCE: The present study might be a transitional study to show the efficacy of GHRP-2 in enhancing bone-tendon healing and reduce retear rate after rotator cuff repair.
Robust growth hormone responses to GH-releasing peptide 2 in adolescents.
Onuki T, Hiroaki T, Sawano K, Shibata N, Nyuzuki H, et al. — 2024
OBJECTIVES: GH-releasing peptide-2 (GHRP2) can be used for provocative growth hormone testing (GHT). Since it acts as a powerful stimulus for GH secretion, cut-off peak GH level in GHRP2 loading test (GHRP2T) is higher than in other GHT. Nevertheless, data on response at adolescents are limited. This report aimed to investigate peak GH levels in GHRP2T in adolescents. METHODS: Clinical data of adolescents after onset of puberty who underwent GHRP2T at our institution from May 2010 to March 2023 were collected retrospectively. Subjects were classified into three groups according to underlying diseases. RESULTS: A total of 23 patients were included: 12 in organic or genetic GHD (o/gGHD) group, three in idiopathic GHD (iGHD) group, and eight in short stature (SS) group. The median GH peak levels were 3.4 ng/mL in o/gGHD group, 88.9 ng/mL in iGHD group, and 90.1 ng/mL in SS group, indicating a robust response of GH peak levels in iGHD and SS groups. Two patients exceeded the cut-off for GHRP2T but below for other GHT, indicating the current cut-off for GHRP2T may miss some GHD patients. CONCLUSIONS: The GH response to GHRP2T in adolescents except the o/gGHD group may be robustly responsive. For the correct diagnosis of GHD, the cut-off peak GH levels in GHRP2T in adolescents may require revisiting.