The short version of secretagogue fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2025-12-09 and is reviewed periodically as new material appears.
Ipamorelin is a synthetic pentapeptide that belongs to the growth hormone secretagogue family. Its sequence is Aib-His-D-2-Nal-D-Phe-Lys-NH2, incorporating two non-natural residues that resist enzymatic breakdown. Researchers at Novo Nordisk described the compound in the 1990s while searching for agents that release growth hormone with fewer side effects than earlier secretagogues. The molecule acts as an agonist at the ghrelin receptor, also called GHS-R1a, which is expressed in the pituitary and in several peripheral tissues.
Selectivity distinguishes ipamorelin from first-generation secretagogues such as GHRP-6. At doses that reliably raise growth hormone, it shows little stimulation of adrenocorticotropic hormone or cortisol release in animal models, and it does not markedly raise prolactin or appetite. Binding at GHS-R1a on pituitary somatotrophs triggers calcium influx and pulsatile growth hormone secretion. Because the compound mimics the natural ghrelin signal, the release pattern tends to follow the body's own rhythm rather than producing a sustained elevation.
Ipamorelin 是一种合成五肽，序列为 Aib-His-D-2-Nal-D-Phe-Lys-NH2，分子式 C38H49N9O5，游离碱分子量约 711.85 g/mol。它属于生长激素促分泌素（GHS）家族，作用靶点是胃饥饿素受体 GHS-R1a。该化合物由诺和诺德的研究团队在二十世纪九十年代末报道，设计目标是提高对生长激素释放的选择性。C 端酰胺化与 N 端 Aib 残基是两个用于抵抗肽酶降解的结构特征。
在 GHS 家族中，早期肽类如 GHRP-6 与 GHRP-2 会同时促进生长激素、皮质醇与催乳素的释放，并明显增加食欲。Ipamorelin 在动物与早期人体研究中表现出对生长激素释放的相对选择性，对上述其他激素的影响较小。这种差异通常归因于受体结合模式与下游信号偏向的不同，而完整的分子解释仍有待补充。需要区分的是，选择性是研究观察中的相对程度，并非绝对界限。
从用途定位看，ipamorelin 目前主要以研究用肽的身份被讨论，未见主要药品监管机构将其批准为治疗药物。市售材料通常标注仅供研究使用，不得用于人体或诊断程序。文献中它常与生长激素促分泌素、GHS-R1a 激动剂、胃饥饿素拟似物等表述并列出现。既有研究的样本量普遍偏小，因此对其效应强度与一致性的描述应保持谨慎。
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C38H49N9O5 | Includes two non-natural residues |
| Molecular weight | About 711.9 g/mol | Confirmed by mass spectrometry |
| Appearance | White to off-white powder | Typical lyophilized form |
| Receptor target | GHS-R1a | Ghrelin receptor agonist |
| Plasma half-life | Roughly 2 hours | Varies by species and assay |
At the receptor level, ipamorelin binds GHS-R1a and triggers signaling through Gq-coupled pathways. Activation leads to calcium release and downstream effects in pituitary somatotroph cells. These events promote the release of growth hormone into circulation. The response depends on the presence of the receptor and on the physiological state of the animal or tissue studied. Because the receptor is also found in other tissues, effects beyond the pituitary have been examined in laboratory models, though the extent of those effects remains an area of ongoing study.
One distinguishing feature reported in animal studies is selectivity. Ipamorelin stimulated growth hormone release with limited elevation of adrenocorticotropic hormone or cortisol compared with earlier secretagogues such as GHRP-6. This pattern has been described as more selective for the growth hormone axis. The finding comes mainly from preclinical work, and the degree to which it holds across species and doses is not fully settled. Reports also describe effects on gastric motility in animal models, suggesting activity outside the pituitary, though the clinical relevance of this observation is uncertain.
Selectivity is the property most often attached to this peptide. Published animal and early human studies record increases in growth hormone release after administration, with adrenocorticotropic hormone and cortisol responses remaining small by comparison. Effects on appetite-related pathways also appear weaker than those reported for several earlier secretagogues. Reviews that compare members of the growth hormone secretagogue family cite these findings frequently, though the receptor-level explanation for the selectivity continues to be debated rather than settled.
Ipamorelin is a synthetic pentapeptide classified as a growth hormone secretagogue. Its sequence, Aib-His-D-2-Nal-D-Phe-Lys-NH2, combines three non-proteinogenic residues with a C-terminal amide. The N-terminal aminoisobutyric acid unit and the two aromatic D-amino acids distinguish it from peptides assembled only from standard L-amino acids. Its formula is C38H49N9O5, corresponding to an average mass near 711.9 Da. At neutral pH the molecule carries a net positive charge, a property that shapes its behaviour in chromatographic and electrophoretic systems.
The compound was developed at Novo Nordisk during the 1990s as part of a programme seeking secretagogues with improved selectivity. It was described in the peer-reviewed literature in 1998 alongside related pentapeptides from the same series. Investigators advanced it because it raised growth hormone output in animal models while leaving other pituitary hormones comparatively unaffected. The development code NNC 26-0161 appears in earlier reports, and ipamorelin later became the common designation in published work.
在机制层面，ipamorelin 与生长激素促分泌受体 1a 型结合，该受体也介导胃饥饿素的多种效应。受体激活后，细胞内信号促进生长激素从垂体前叶释放。由于对促肾上腺皮质激素和皮质醇的刺激较弱，它被视为选择性较高的促分泌剂。这种选择性在动物模型和少量人体研究中被观察到，但人体数据仍然有限。
现有文献多来自小规模、短期的研究，涉及生长激素缺乏、术后肠麻痹等方向。长期使用是否导致受体脱敏，以及重复给药后效应是否衰减，仍属开放问题。不同研究之间的剂量、给药途径和受试者特征差异较大，因此结论外推需谨慎。关于临床获益的确切证据尚不充分，需要更大规模的对照试验来澄清。
Ipamorelin is a synthetic pentapeptide that acts as an agonist at the ghrelin receptor, also called the growth hormone secretagogue receptor type 1a. Its sequence incorporates non-natural residues, which slows enzymatic breakdown relative to short native peptides. In laboratory and early clinical work the compound is described as a selective growth hormone secretagogue because it raises growth hormone with comparatively little effect on other pituitary outputs. The degree to which that selectivity holds across species and dosing regimens remains an open question in the published literature.
Signal transduction begins when the peptide binds GHSR-1a on pituitary somatotrophs. The receptor couples to Gq/11 proteins, activating phospholipase C, which cleaves phosphatidylinositol bisphosphate into inositol trisphosphate and diacylglycerol. Inositol trisphosphate releases calcium from intracellular stores, and the resulting rise in cytosolic calcium drives growth hormone vesicle fusion. Concurrent Gs coupling and cyclic AMP elevation have also been reported, and the relative contribution of each arm to the overall secretory response is not fully settled.
As of 24 January 2007, Smucker said that all Crisco shortening products in the US had been reformulated to contain less than one gram of trans fat per serving while keeping saturated fat content less than butter. The separately marketed trans fat free version introduced in 2004 was discontinued. On 22 May 2004, Unilever, the corporate descendant of Joseph Crosfield & Sons (the original producer of Wilhelm Normann's hydrogenation hardened oils) announced that they had eliminated trans fats from all their margarine products in Canada, including their flagship Becel brand. Agribusiness giant Bunge Limited, through their Bunge Oils division, produce an NT product line of non-hydrogenated oils, margarines and shortenings, made from corn, canola, and soy oils.
=== 16 August === At least 31 people were killed in RSF shelling on the Abu Shouk camp. The SAF destroyed 4,500 landmines, shells and other munitions recovered near Khartoum in a controlled detonation at the Wadi Seidna garrison as part of cleanup efforts. One person was killed in a grenade attack inside the main hospital of Zalingei.
=== Inflammation === In inflammatory conditions, fibrinogen, other clotting proteins, and alpha globulin are positively charged, thus increasing the ESR. ESR begins to rise at 24 to 48 hours after the onset of acute self-limited inflammation, decreases slowly as inflammation resolves, and can take weeks to months to return to normal levels. For ESR values more than 100 mm/hour, there is a 90% probability that an underlying cause would be found upon investigation.
Sources: en.wikipedia.org
After at least three months, other effects are expected, such as the deepening of the voice and changes in sexual organs (such as atrophy of vaginal tissues, and increased clitoral size). Regular monitoring by an endocrinologist is a strong recommendation to ensure the safety of individuals as they transition. Access to hormone replacement therapy has been shown to improve quality of life for people in the female-to-male community when compared to female-to-male people who do not have access to hormone replacement therapy. Feminizing therapy has also been found to improve well-being. Interestingly, one systematic review determined that "Overall, the qualitative literature tended to support positive changes in well-being among people after starting feminizing hormone therapy, although often with the qualification that improvements in well-being were attributed to satisfaction with changes in appearance rather than to direct effects of hormones on psychosocial states." Hormone therapy for transgender individuals has been shown in medical literature to be safe, when supervised by a qualified medical professional. Monitoring of risk factors associated with hormone replacement therapy, such as prolactin levels in transgender women and polycythemia levels in transgender men, are crucial for the preventive health care of transgender people taking these treatments. Many transgender people lack access to a supportive, high quality, non-discriminatory health care system.
The first body segment (segment number 1) features both the earthworm's mouth and, overhanging the mouth, a fleshy lobe called the prostomium, which seals the entrance when the worm is at rest, but is also used to feel and chemically sense the worm's surroundings. Some species of earthworm can even use the prehensile prostomium to grab and drag items such as grasses and leaves into their burrow. An adult earthworm develops a belt-shaped glandular swelling, called the clitellum, which covers several segments toward the front part of the animal. This is part of the reproductive system and produces egg capsules. The posterior segment is most commonly cylindrical like the rest of the body, but depending on the species, it may also be quadrangular, octagonal, trapezoidal, or flattened. The last segment is called the periproct; the earthworm's anus, a short vertical slit, is found on this segment.
== Role in cancer == Lazaris-Karatzas et al. found that that over-expressing eIF4E causes tumorigenic transformation of fibroblasts. Since this initial observation, numerous groups have recapitulated these results in different cell lines. As a result, eIF4E activity is implicated in several cancers including cancers of the breast, lung, and prostate. In fact, transcriptional profiling of metastatic human tumors has revealed a distinct metabolic signature wherein eIF4E is known to be consistently up-regulated. eIF4E levels are increased in many cancers including acute myeloid leukemia (AML), multiple myeloma, infant ALL, diffuse large B-cell lymphoma, breast cancer, prostate cancer, head and neck cancer and its elevation generally correlates with poor prognosis. In many of these cancers such as AML, eIF4E is enriched in nuclei and several of eIF4E's activities are found to be elevated in primary patient specimens, including capping, splicing, RNA export, and translation. In the first clinical trials targeting eIF4E, old antiviral drug ribavirin was used as a m7G cap competitor which had substantial activity in cancer cell lines and animal models associated with dysregulated eIF4E. To date PubMed searches reveal that over 30 groups have found that ribavirin targets eIF4E activity while two did not. In the first trial to ever target eIF4E, ribavirin monotherapy was demonstrated to inhibit eIF4E activity leading to objective clinical responses including complete remissions in AML patients.
These multidisciplinary teams leverage the Barshop Institute's nationally recognized aging research programs—including the Nathan Shock Center of Excellence in the Basic Biology of Aging, the Claude D. Pepper Older Americans Independence Center, the Center for Alzheimer's Disease and Related Dementias Population Aging and Social Studies (CAPAS), and the Interventions Testing Program—to rapidly translate mechanistic discoveries into human studies. This integrated research environment enables investigators to evaluate interventions targeting the fundamental biological mechanisms of aging rather than focusing solely on individual diseases, reflecting the principles of geroscience that underpin the Institute's research mission. A landmark addition to the Institute's clinical research portfolio is the Validation and Intervention Testing for Aging, Longevity and Healthspan (VITAL-H) clinical trial, supported by a contract of up to $38 million from the Advanced Research Projects Agency for Health (ARPA-H) through its Proactive Solutions for Prolonging Resilience (PROSPR) program. As the coordinating center for this first-of-its-kind national healthspan clinical trial, the Barshop Institute is leading an unprecedented effort to determine whether FDA-approved medications can slow the biological processes of aging and preserve health and functional capacity before the onset of chronic disease.
Sources: en.wikipedia.org
=== Project CONCERT === The aim of the CONCERT (European Joint Programme for the Integration of Radiation Protection Research) project is to establish a joint European program for radiation protection research in Europe in 2018, based on the current strategic research programs of the European research platforms MELODI (radiation effects and radiation risks), ALLIANCE (radioecology), NERIS (nuclear and radiological emergency response), EURADOS (radiation dosimetry) and EURAMED (medical radiation protection).
Mirubactin is a siderophore produced by the bacterium Actinosynnema mirum. A. mirum was first isolated from the Raritan River in New Jersey in 1976, and its full genome sequence was published in 2009. In 2012, mirubactin was isolated and characterized, and the biosynthesis was connected with the gene cluster Amir_2714-Amir_2728, since renamed mrbA-mrbO.
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==== Laser-assisted nonpenetrating deep sclerectomy ==== The most common surgical approach currently used for the treatment of glaucoma is trabeculectomy, in which the sclera is punctured to alleviate intraocular pressure. Nonpenetrating deep sclerectomy (NPDS) surgery is a similar, but modified, procedure, in which instead of puncturing the scleral bed and trabecular meshwork under a scleral flap, a second deep scleral flap is created, excised, with further procedures of deroofing the Schlemm's canal, upon which, percolation of liquid from the inner eye is achieved and thus alleviating intraocular pressure, without penetrating the eye. NPDS is demonstrated to have significantly fewer side effects than trabeculectomy. However, NPDS is performed manually and requires higher level of skills that may be assisted with instruments. In order to prevent wound adhesion after deep scleral excision and to maintain good filtering results, NPDS as with other non-penetrating procedures is sometimes performed with a variety of biocompatible spacers or devices, such as the Aquaflow collagen wick, ologen Collagen Matrix, or Xenoplast glaucoma implant. Laser-assisted NPDS is performed with the use of a CO2 laser system. The laser-based system is self-terminating once the required scleral thickness and adequate drainage of the intraocular fluid have been achieved.
== Mechanism == The protein obeys Michaelis-Menton kinetics and has an associated KM of 278 ± 49 μM. The GYDQL and YFPQA motifs on the C-terminal binds cystinosin to the lysosome. Mutations in the GYDQL motif cause a repositioning of cystinosin to being partially on the plasma membrane and partially on the lysosome. Mutations in both GYDQL and YFPQA motifs cause cystinosin to position itself to the plasma membrane instead of lysosomes An increase in acidity in the lumen of the lysosome initiates the reaction of CySS and H+ being transported into the cytosol.
Sources: en.wikipedia.org
The peptide is Aib-His-D-2-Nal-D-Phe-Lys-NH2. Two of its residues are non-natural, which slows enzymatic degradation. The C-terminal amide is common among bioactive peptides.
It binds the same ghrelin receptor but with greater selectivity in functional assays. Preclinical work reports less cortisol and prolactin stimulation at growth-hormone-releasing doses. Those differences are relative, not absolute, and depend on dose and model.
No major regulatory authority has approved it for human therapeutic use. It is sold as a research chemical for laboratory investigation. Clinical status varies by country and is subject to change.
两者都是 GHS-R1a 激动剂，但 ipamorelin 在研究中显示出更高的生长激素释放选择性。早期资料显示它对皮质醇、催乳素与食欲的刺激弱于 GHRP-6。这些差异是相对程度，而非绝对区分。