Everybody who looks at Nitin Paul (name changed) marvels at his height. He is only 14, but is already 6 feet 4 inches tall. Curiously, his parents are of average height. Could the Calcutta schoolboy be suffering from a disorder called gigantism?

Gigantism — a condition that leads to excessive growth — occurs when the pituitary or thyroid gland release excess hormones. But a study published recently in the Journal of Biological Chemistry implies that there may be a remedy — over time — for such hormone disorders.

Scientists have known for a while that many critical life processes controlled by the hormones are affected even when their production by glands is normal. This usually happens because the hormones are not released when they are needed.

Hormones regulate processes that are crucial for healthy functioning. Many of these hormones — including insulin, glucagon and the growth hormone — are protein or peptide molecules that are synthesised by the body and stored in cells known as secretory granules in clumps called amyloids. These amyloids are released into the blood stream as and when required by the body. For example, insulin, which plays an important role in sugar metabolism, is released from the pancreatic cells in response to glucose levels in the blood stream.

Scientists at the Indian Institute of Technology (IIT)-Bombay have now discovered that the problem lies in the structural changes that take place in these amyloids.

“The structure or shape of a protein could be crucial for its efficient storage and secretion. Therefore, in most cases, structure governs the function of a protein,” explains Samir Kumar Maji, who heads the research team.

With his team, Maji, who is an assistant professor in the department of biosciences and bioengineering at IIT-Bombay, is trying to work out why the stored hormones are not always released.

The group studied the role played by the structure of a peptide hormone called somatostatin-14 (SST14), which is involved in several functions of the human body, the most well known of which is countering a excessive growth hormone secretion, thus regulating human growth. Other important functions include controlling gastric acid secretion and insulin and glucagon secretion in the pancreas. A deficiency of this hormone can lead to gigantism and pituitary adenoma or non-cancerous tumours in the pituitary gland.

The researchers who carried out studies on a lab rat found that the structure of SST-14, which is stored in an amyloid form, could change in abnormal cases. And this happened when a particular chemical bond (disulphide bond) which kept it stable was disturbed. This caused the protein to take on a different structure, resulting in faster amyloid formations. These amyloids, however, do not release the somatostatin hormone readily.

“Our findings emphasise that subtle discrepancies in the protein structure could lead to reduced secretion of the hormone, resulting in serious hormone-related disorders,” adds Ashutosh Kumar, assistant professor at IIT-Bombay and a member of the research team.

The scientists, who hope to study this in bigger animals in the future, are now figuring out whether these results are applicable to other hormones too.

“This is undoubtedly an important paper aimed at solving a complex puzzle,” Dr Sudipta Maiti, a scientist and professor at the Tata Institute of Fundamental Research, says. “It shows that the difference between people who have abnormal growth hormone releases and those who don’t may lie in their somatostatin structure. This may help pharmaceutical companies hone their strategy for attacking this disorder,” Dr Maiti, who works on the amyloid-associated Alzheimer disease, adds.

Dr Tamoghna Maiti, associate professor of pharmacology, Bankura Sammilani Medical College, describes it as a “great” finding. “Now, if experts can create long-acting somatostatin outside the human body, it can be used to treat dwarfism and pituitary deficient newborns too. Besides, this type of somatostatin can also be used to repair body tissue.”