Growth hormone, GHRH analogues and secretagogues sit at three different points of one pathway. Knowing which is which is most of what a reader needs.
The pituitary gland releases growth hormone in pulses, but only when told to. The instruction comes from the brain as growth hormone-releasing hormone, and a second trigger acts through the ghrelin receptor. Compounds in this category act at one of three positions: the hormone itself, the releasing signal, or the receptor trigger. Evidence gathered at one position does not describe the others.
Growth hormone (GH) is a 191-amino-acid protein made by the anterior pituitary. It is not released continuously. The hypothalamus sends growth hormone-releasing hormone (GHRH), which acts on its own receptor on pituitary cells and prompts a pulse. Separately, the ghrelin receptor on the same cells can be activated by ghrelin, better known as a hunger signal, and produces a pulse by a second route. Once in the blood, GH acts directly on muscle, bone, fat and liver, and prompts the liver to make IGF-1 (insulin-like growth factor 1), a second hormone that carries much of the downstream signal (Ranke and Wit 2018).
So there are three places to act: supply the hormone, send the releasing signal, or press the second trigger.
Somatropin is recombinant human growth hormone, the exact human sequence made in engineered cells; ‘191AA’ in a product name signals that form. It bypasses the pituitary entirely. Its evidence base is the largest in this category, built over decades of randomised trials in children with growth disorders and adults with confirmed deficiency, and it is a Schedule 4 medicine in Australia for those indications. Research in people without deficiency is a separate and more contested literature, in which changes in lean mass have generally not translated into measured functional gains.
Because it supplies the hormone directly, its results do not show whether the pituitary can be prompted to make more.
GHRH analogues copy the brain’s instruction. Native GHRH is destroyed within minutes by the enzyme DPP-IV, so the analogues are built to survive it. Tesamorelin keeps the full 44-amino-acid sequence with one chemical cap, and it is the compound in this category that went through phase 3: two randomised trials in adults with HIV who had accumulated abdominal fat reported reduced visceral fat on CT (Falutz et al. 2007), leading to US approval for that indication only. CJC-1295 uses the first 29 residues with four substitutions; the DAC form adds a group that bonds to albumin so the signal lasts days. Its human data are small phase 1 studies in healthy adults measuring GH and IGF-1 (Teichman et al. 2006), not clinical outcomes, and they concern the DAC form, not the ‘without DAC’ backbone.
A releasing signal only works if the pituitary can respond. That dependence is the point of the category and also its limit.
Growth hormone secretagogues act at the ghrelin receptor. Ipamorelin was characterised in rat pituitary cells, rats and pigs as the first such peptide with selectivity for GH release, without the cortisol rise seen with earlier compounds in the pig model (Raun et al. 1998); its one randomised clinical trial, in bowel-surgery recovery, found no effect on its endpoint. Hexarelin, an older six-residue peptide, raised GH in healthy adults by several routes but also raised cortisol and prolactin, and the response declined with repeated dosing (Ghigo et al. 1994). Reviews describe the clinical data for secretagogues in body-composition settings as largely lacking (Sinha et al. 2020).
Selectivity shown in pigs is a property of that experiment. It is not a property of the class.
The pattern is not unique to growth hormone. Reproductive hormones are released along a similar chain: kisspeptin in the brain prompts the releasing signal GnRH; the pituitary responds with luteinising hormone; and the ovary or testis makes oestrogen or testosterone. hCG acts at the far end of that chain, on the same receptor luteinising hormone uses, so it is a hormone standing in for a hormone, while kisspeptin is an upstream signal (Dhillo et al. 2005; Cole 2010). PT-141 belongs to neither chain: it activates melanocortin receptors in the brain, a receptor trigger in a different system. The reading rule is the same: evidence gathered at one position describes that position.
A trial of somatropin in deficient children measured what supplied hormone does in people who cannot make enough. A trial of tesamorelin in adults with HIV measured what a protected releasing signal does to one fat depot in that population. A pig study of ipamorelin measured a hormone pulse. None of these describes another compound, another position, or another population. No published trial of the CJC-1295 and ipamorelin pairing sold as a blend was identified. Growth hormone, releasing factors and secretagogues are all prohibited in sport under WADA category S2, which is one thing they do share.
Sources checked 2026-09-22