Increased number of ghrelin producing cells in PWS

Here is an article in which the authors investigated why people with PWS have high levels of ghrelin in their blood. They wondered if perhaps it had something to do with growth hormone (GH) deficiency, which is common in PWS.

Ghrelin was actually first recognized by the fact that it stimulates the secretion of growth hormone in the brain- the relationship between ghrelin and appetite was later appreciated. It has been noted recently that people with GH deficiency may have higher levels of ghrelin than normal (but presumably not the great increase in appetite). [side note here: one possibility is that the excess ghrelin in the blood is really due to the body trying to get the brain to secrete more GH, and that increased ghrelin and appetite in PWS is just a by-product of the GH axis problem -- this may not be the case, though, since ghrelin doesn't seem to go down with GH administration, as some had hoped].

Here the authors asked whether the ghrelin secreting cells in the stomach were similar in PWS compared to individuals with GH deficiency, but not PWS. So they took biopsies from the stomachs of 16 individuals with PWS, 13 individuals with GH deficiency (but not PWS), and some lean and obese controls. When they counted how many ghrelin producing cells were in each sample, they found that there are 2-3 times more ghrelin producing cells in the stomachs of people with PWS. Apparently, that's why there are very high levels of ghrelin in people with PWS, even if they are obese. They also found that there did not seem to be a discernable relationship between ghrelin producing cells/ghrelin levels and the GH axis.

Some questions this raises -- why are there more ghrelin producing cells in the stomachs of those with PWS? -- are they born that way, or is that something that changes as time goes on. What is the basis of increased circulating ghrelin in GH deficient patients? If this is correct, why aren't GH deficient patients hungry too? Is the high ghrelin concentrations in PWS related to low insulin levels that appears common in this group (chicken and the egg)? Is ghrelin truly the basis of the increased appetite in PWS, or is it a red herring?

It is also significant that this suggests that all of the problems in PWS may not lie in the hypothalamus, but rather in peripheral tissues as well.

Increased density of ghrelin-expressing cells in the gastric fundus and body in Prader-Willi syndrome.Choe YH, Song SY, Paik KH, Oh YJ, Chu SH, Yeo SH, Kwon EK, Kim EM, Rha MY, Jin DK. J Clin Endocrinol Metab. 2005 Sep;90(9):5441-5, 2005.

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Theresa Strong

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Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.

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