How Does Human Growth Hormone Work?

The following article was written by user ‘canal_of_schlemm‘ from r/steroids Reddit

Growth Hormone

Growth hormone (GH) is a peptide hormone that is synthesized and released by somatotroph cells in the pars distalis of the pituitary gland. It belongs to a family of hormones known as the growth hormone family. This also includes prolactin (PRL) and placental lactogen. Despite the obvious differences in function, these hormones share a very similar structure. Likewise, GH and PRL are the only two non-tropic hormones synthesized and released from the anterior pituitary gland.

The synthesis and release of GH is directly regulated through its two hypophysiotropic hormones, growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH, or somatostatin). Despite the direct regulation by these hormones, other hormones can affect the secretion of GH. Thyroid hormones are shown to have a direct effect on GH synthesis, ghrelin through the activation of the growth hormone secretatgoguge receptor (GHSR), and much like PRL, GH synthesis is directly downregulated by dopamine and dopamine agonists such as bromocriptine.

GHRH is synthesized in the arcuate and ventromedial nuclei of the hypothalamus while GHIH is primarily synthesized in the anterior periventricular region of the hypothalamus. These two hormones are in constant flux. Both hormones act on their respective receptors on the surface of somatotroph cells, where they activate second messenger systems that affect gene expression and calcium concentrations. When GHRH binds, GH gene expression is activated and intracellular levels of calcium increase to stimulate the exocytosis of GH. When GHIH binds, the inverse happens as a result of inhibitory G proteins on the receptor that fail to activate adenylate cyclase.

GH is naturally released in a pulsatile manner. This means that release of GH occurs in short bursts throughout the day rather than a constant release. Over half of our natural GH release occurs during deep sleep during stages 3 and 4. As we age and GH levels decline, it is a direct effect lower concentrations during these bursts rather than a decline in the number of bursts themselves. Because of this pulsatile manner, the detection of GH in the blood is not conclusive, and typically insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) levels are checked as they are kept more constant and their existence is a direct result of GH stimulation.

While GH does have independent effects in the body, majority of the effects are a result of IGF-1 activity. During adolescence, GH will have direct growth-promoting actions on progenitor and stem cells. Specifically, prechondrocytes in epiphyseal plates of long bone which induce longitudinal growth and satellite cells of skeletal muscle which induce myocyte differentiation. This occurs due to GH stimulating these cells to synthesize IGF-1 which has an autocrine and paracrine mitogenic effect, causing the progenitor cells and nearby cells to undergo mitosis.

IGF-1

As mentioned early, IGF-1 is a mitogenic agent that mediates the intended effects of GH. This peptide hormone is produced by many of the cells in the body, but the majority is synthesized in the liver. Most IGF-1 in blood is bound to IGFBP3 and very little circulates freely. Because of this, IGF-1 has no role in blood glucose regulation like its name might suggest.

Growth Hormone Secretagogues

GHSs are drugs that act as an agonist for the GHRH receptor and the growth hormone secretagogue receptor (GHSR). Endogenously, ghrelin is the primary ligand for GHSRs and they can increase the synthesis of GHRH. The two most prominent GHSs in bodybuilding would be CJC-1295 and GHRP-6.

  • CJC-1295: CJC-1295 is a GHRH receptor agonist. Despite promising results in the increase of IGF-1, clinical trials were disrupted by the death of a participant.
  • GHRP-6: GHRP-6 is a GHSR agonist. GHRP-6 is said to mimic the effects of ghrelin. Unfortunately, ghrelin has been recently linked to the proliferation of many different types of cancer through signaling action of GHSR.

Regulation

  • Stimulation: Stimulation of GH, or more specifically GHRH, is typically induced by low blood glucose levels. Overall, GH is a glucose-sparing hormone, similar in sense to epinephrine and cortisol. Because of this, physiological and emotional stress can increase GH secretion. Many pharmacological agents are shown to stimulate GH secretion as well, including L-dopa, clonidine, propanolol, glucagon, insulin, and arginine.
  • Inhibition: Like most hormones, GH operates under a negative feedback mechanism. Both high levels of GH and IGF-1 will inhibit GHRH.

Effects

Despite IGF-1 mediating many of the effects of GH, GH will also independently impact the same effectors. GH will induce lipolysis in adipocytes via activation of hormone-sensitive lipase, similar to epinephrine and cortisol. GH will also act in an antagonistic manner towards insulin. Most notably, GH has been shown to inhibit glucose uptake in muscle and bone. This is due to GH inhibit the Akt kinase phosphorylation that is necessary for insulin-mediated Glut-4 translocation. Essentially, GH will inhibit insulin from shuttling glucose into muscle. Similarly, GH will stimulate hepatic gluconeogenesis. Due to these major glucose-sparing effects and inhibition of Glut-4 translocation, GH is referred to as a diabetogenic hormone. Development of type II diabetes is common amongst patients with excessive GH levels and this places bodybuilders at risk, especially when utilized with insulin.

There have been different studies that state that GH either increases or decreases SHBG levels, however it has been confirmed that exogenous GH usage does not impact SHBG or free androgen levels. GH users may experience an increase in appositional bone growth, specifically in flat bone. This occurrence is known as Acromegaly. Joint pain and carpal tunnel syndrome are also common in those with high GH levels. A possible link to Hodgkin’s lymphoma is also being investigated.

7 Responses

  1. John

    If an adolescent was given GH would it cause extra growth in terms of height and other variables? I guess I’m asking do taller people mean that more GH was released during adolescence?

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  2. […] A good addition to any cycle, had anti aging properties, can promote deeper sleep, fat loss, muscle growth, healthier hair and skin, pharmaceutical grade HGH can be used but is expensive, lots of people opt for Chinese ‘generic’ growth hormone which has proved to be good quality from some suppliers, usually used at 4 to 6 units per day – more about HGH here […]

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