Get a grip on your hormones
OUR day-to-day behaviour depends on the hormonal balance in our bodies. Whether we want to eat, drink or sleep depends on the hormonal status of our system at any given moment. It is well known that hormones are released by the anterior pituitary gland, which is stimulated by the part of the brain known as hypothalamus. J C Meunier of the National Centre of Scientific Research, Toulouse, France, has come out with some interesting work on the isolation of pep-tide factors (protein compounds in which two or more amino acid molecules are linked in a linear sequence). These factors stimulate the release of prolactin, the hormone responsible for formation of milk in female mammals (Nature, Vol 393, No 6682).
The work represents an unusual example of the discovery of a biologically-active factor based on the knowledge of its target, rather than the other way round, as is usually the case. The first step was to clone the gene for a cell-surface receptor molecule belonging to a ubiquitous family, the so-called G protein-coupled receptors. But in this instance it was not known what the natural stimulus was. The receptor was an 'orphan'. But the orphan receptor's DNA sequence was similar to that of other peptide-activated receptors belonging to its class, and the gene for the receptor was strongly expressed in the pituitary. Both were significant clues.
But what was the stimulus that the receptor was naturally responsive to? In order to find out, the researchers examined various extracts from bovine hypothalamus and discovered that the extracts were effective in eliciting the release of a cellular lipid known to promote the release of prolactin. Using this to estimate stimulus quality, they pinned down the effect to two peptides of 19 and 29 amino acid molecules in length. Under laboratory conditions, the larger peptides successfully stimulated the release of prolactin from cultured pituitary cells.
Now that a chemically pure preparation has been shown to stimulate prolactin release, the way is open for applications in pharmacology and medicine.
Excessive release of prolactin may be controlled by administration of antagonists to the peptide factors. Conversely, a lack of prolactin could be treated by administering the peptide(s). Apart from its implications for therapy, this work is interesting because of its 'upside-down' nature: a pharmacologically active drug has been identified by searching for what might effectively stimulate its supposed target.