Tintin's Blight
By Vivienne Baillie Gerritsen
Tintin never grew up. Readers followed his travels around the world for almost fifty years and yet the Belgian journalist showed no signs of aging whatsoever. No grey hair, no wrinkles, no loss of stamina. He never changed style either; he never seemed to tire of his knickerbockers nor of his cranial crest. But that is beside the point… How can a human span a lifetime looking as though he never grew older than the age of fifteen? Hypogonadotropic hypogonadism or HH say some. HH is a condition in which the subject who is inflicted with it never reaches puberty. Typically, in a man, this would mean that he shows no signs of becoming one, i.e. in growing facial hair for example or being the proud owner of a mature reproductive system. Tintin never took his pants down but any of his readers know that he certainly never showed signs of growing a beard. HH in a man is caused when the regulation of the male hormone, testosterone, is deficient. And we now know of one protein which seems to have a key role in such a regulation: the KiSS-1 receptor.
How does a condition like HH occur in the first place? It all has to do with hormones. Naturally. Puberty is triggered off by a flush of hormones, amongst which are those that cause a young boy to grow hair on his chin or a girl to menstruate. If such hormones are hindered in any way, a young boy will never know the joys of a beard, or a razor. At puberty, a part of our central nervous system, the hypothalamus, releases a hormone known as ‘gonadotropin-releasing hormone’ which itself causes the release of two other hormones – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) – which are both produced in a small gland – the pituitary gland – situated just beneath the hypothalamus. In young boys, FSH and LH ultimately cause the production of testosterone. If the hypothalamus-pituitary gland pathway is hindered in any way, the production of the male hormone will be also and puberty will not take on its proper course.
A number of instances can cause hypogonadotropic hypogonadism. Key hormone receptors involved in the pathway can be deficient or missing due to surgery, head trauma or a congenital disease for instance. It was the study of congenital HH which led to the discovery of the KiSS-1 receptor which proved to have a direct role in the proper development of the male and female gonads. The KiSS-1 receptor is found both in the hypothalamus and the pituitary gland and is a G protein-coupled receptor; that is to say it belongs to the very large family of transmembrane receptors whose role is to transduce a signal. Its ligand is the neuropeptide KiSS-1 and together they are involved in the regulation of gonadotropin secretion. As mentioned above, gonadotropin ultimately stimulates the production of testosterone in males. Take away the KiSS-1 receptor and Tintin becomes Peter Pan.
Fig. 1Tintin in the land of Gold, Hergé, Ed. Casterman