Monday, December 12, 2011

Grow Taller with Growth Hormone Binding Protein

In our study of Growth Hormone, we found that(in mice at least) that Growth Hormone and IGF-1 increased levels of GHR and GHBP.  And, that things that reduced height like dexamethasone lowered levels of GHBP and that things that increased height like thyroid hormone increased levels of GHBP.

Here's a study that shows which proteins active GHBP(and thus potentially which proteins we can manipulate):

The Extracellular Domain of the Growth Hormone Receptor Interacts with Coactivator Activator to Promote Cell Proliferation

"The presence of GH receptor (GHR) in the cell nucleus correlates with cell division[cell division is really good for growth plate chondrocytes and means more height growth], and targeting the GHR to the nucleus results in constitutive proliferation and transformation because of increased sensitivity to autocrine GH. Here we have sought additional mechanisms that might account for the enhanced proliferation seen with nuclear GHR, commencing with a yeast two-hybrid (Y2H) screen for interactors with the extracellular domain of the GHR [GH-binding protein (GHBP)]. We find that the GHBP is a transcriptional activator in mammalian cells, and this activity resides in the lower cytokine receptor module. Activity is dependent on S226, the conserved serine of the cytokine receptor consensus WSXWS box. By using parallel GHBP affinity columns and tandem mass spectrometry of tryptic digests of proteins bound to wild-type GHBP and S226A columns, we identified proteins that bind to the transcriptionally active GHBP. These include a nucleoporin and two transcriptional regulators, notably the coactivator activator (CoAA), which is also an RNA binding splicing protein. Binding of CoAA to the GHBP was confirmed by glutathione S-transferase pulldown and coimmunoprecipitation, and shown to be GH dependent in pro-B Ba/F3 cells. Importantly, stable expression of CoAA[the protein that binds to GHBP] in Ba/F3 cells resulted in an increased maximum proliferation in response to GH, but not IL-3[therefore if we stabilize the CoAA protein we will increase the cell response to GH]. Because CoAA overexpression has been identified in many cancers and its stable expression promotes cell proliferation and cell transformation in NIH-3T3 cells, we suggest CoAA contributes to the proliferative actions of nuclear GHR by the hormone-dependent recruitment of this powerful coactivator to the GHR."

So increase levels of CoAA to grow taller.

According to the study "The Coactivator activator CoAA regulates PEA3 group member transcriptional activity.": "Five CoAA interactors have been identified previously: the coactivator TRBP and the histone acetyltransferase CBP, the proto-oncogene coactivator SYT, the extracellular domain of the GH (growth hormone) receptor called GHBP (GH-binding protein), and the transcription factor RUNX2"<-So a likely way to manipulate CoAA is via RUNX2.  Diosgenin increases RUNX2 levels.  Parathyroid Hormone inhibits Zfp521 which allows for higher RUNX2.

Unfortunately it seems more likely that CoAA stimulates Runx2 than the other way around:

Co-activator activator (CoAA) prevents the transcriptional activity of Runt domain transcription factors.

"Runx factors bind DNA and co-factors to activate or repress genes crucial for bone formation [and] hematopoiesis. Co-activator activator (CoAA) is a nuclear protein that regulates gene expression, RNA splicing and is overexpressed in many human tumors. CoAA [is] a Runx2 binding protein. CoAA repressed Runx factor-dependent activation of reporter genes in a histone deacetylase-independent manner. CoAA also blocked Runx2-mediated repression of the Axin2 promoter, a novel Runx target gene. The carboxy-terminus of CoAA is essential for binding the Runt domains of Runx1 and Runx2. In electophoretic mobility shift assays, CoAA inhibited Runx2 interactions with DNA. These data indicate that CoAA is an inhibitor of Runx factors and can negate Runx factor regulation of gene expression. CoAA is expressed at high levels in human fetal osteoblasts and osteosarcoma cell lines. Suppression of CoAA expression by RNA interference reduced osteosarcoma cell viability in vitro, suggesting that it contributes to the proliferation and/or survival of osteoblast lineage cells."

So CoAA stimulates osteoblasts as well as chondrocytes.  Unfortunately, no way of increasing serum levels of the CoAA protein is known(which would stimulate GHBP).


  1. giants like sultan kosen continued to gain height until 25 when he had an operation to stop any futher growth other giants continue to gain height until late 30s whats your theory have their growth plates remained open how is this possible when growth plates normally close 18 -21 years

  2. Epic Fail Tyler. I expected more from you.

    Hepatic GHR numbers and circulating GHBP levels are regulated by insulin activity [9,10]. Children and adolescents with type 1 diabetes mellitus are relatively GH resistant, reflecting their portal insulin insufficiency [4]. In contrast, increased GH sensitivity in obese children [1] could reflect their hyperinsulinemia, which up-regulates GHBP levels and IGF-I generation and also increases IGF-I bioactivity by lowering levels of IGF binding protein (IGFBP1).


  3. Whats the point in increasing GH sensitivity if the pathway GH uses is disabled? Referring to Janus Kinase 2.

  4. Look, its hakker, the HI clown, researching, but no one cares about his research.