A Simplified View on Signal Transduction Pathways of Human Growth Hormone and its Effect on Cancers

Author: Vaishali Jha

From: East Meadow, NY, US

As are most hormones, somatotropin, or human growth hormone, is very complex in its effects and mechanisms. Human Growth hormone is a hormone that is secreted by the pituitary gland's anterior lobe and is responsible for stimulating cell proliferation for tissue growth and also plays a big role in the liver and other tissue in order for bone growth. Somatotropin is a peptide hormone meaning it doesn’t need to enter the cell in order to work because it interacts with receptors in the cell membrane that triggers multiple signal transduction pathways to activate multiple target genes. To initiate the pathway, somatotropin binds with the growth hormone receptor (GHR) which is embedded in the phospholipid bilayer which then triggers JAK2 to bind to the receptor. JAK2, or Janus kinase 2, is a tyrosine kinase meaning it is an enzyme with the capability of moving a phosphate group from ATP to a tyrosine amino acid of a protein. This transfer is called tyrosyl phosphorylation and is what happens to the JAK2 and GHR activated complex. After the complex is phosphorylated, multiple signaling pathways are activated. The pathway to focus on here is the one involving insulin-like growth factors.

Insulin-like growth factor-1 (IGF-1) is responsible for the stimulation of cartilage cells, or chondrocytes, reproduction which is bone growth. IGF-1 also aids in the differentiation and proliferation of precursor cells for myocytes (muscle cells), otherwise known as myoblasts. Human growth hormone stimulates protein anabolism meaning the creation of protein from amino acids and promotes amino acid reuptake.

There have been studies to support the fact that the increased presence of human growth hormone in hepatocellular carcinoma (HCC) cell lines have promoted cancer stem-cell-like properties. HCC is the most prevalent primary malignant tumor on the liver and often presents

itself in patients with cirrhosis. The mechanisms for this correspondence between HGH and HCC involve the inhibition of the target gene for a specific somatotropin signal transduction pathway. Referencing back to the pathway involving JAK2 and tyrosyl phosphorylation, this phosphorylation triggers multiple signal transduction pathways. One of these pathways involves STAT3 or signal transducer and activator of transcription 3. HGH binding to the receptor triggers STAT3 to go to the target gene through JAK2. STAT3 then inhibits the expression of CLAUDIN-1 which is a transmembrane protein in charge of tight junctions in epithelial cells. Other studies that focus more on tight junctions have shown that the lack of CLAUDIN-1 has led to the development of different epithelial cancers (like HCC). Therefore, the inhibition of HGH expression may present as an option to treat hepatocellular carcinoma or at least slow its growth.

 

Author: Vaishali Jha

Vaishali is a senior at East Meadow High School. Ever since her childhood, she has been infatuated with science. She was raised by two scientists which fueled her interest in biology and shaped her goals of becoming a doctor.

 

Sources:

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  2. Carter-Su, C., Schwartz, J., & Argetsinger, L. S. (2016). Growth hormone signaling pathways. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 28, 11–15. https://doi.org/10.1016/j.ghir.2015.09.002

  3. Growth Hormone (Somatotropin). (n.d.). http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/gh.html#:~:text=The%20major%20role%20of%20growth,)%2C%20resulting%20in%20bone%20growth.

  4. Bhat, A. A., Syed, N., Therachiyil, L., Nisar, S., Hashem, S., Macha, M. A., Yadav, S. K., Krishnankutty, R., Muralitharan, S., Al-Naemi, H., Bagga, P., Reddy, R., Dhawan, P., Akobeng, A., Uddin, S., Frenneaux, M. P., El-Rifai, W., & Haris, M. (2020). Claudin-1, A Double-Edged Sword in Cancer. International journal of molecular sciences, 21(2), 569. https://doi.org/10.3390/ijms21020569



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