There is a strain of mouse in which the regulation of glucocorticoid synthesis is rather unusual; in fact, it does not seem to be regulated at all, the glucocorticoids are present in the blood at a constant, very low concentration. To get at the basis of this abnormality, ACTH was injected into some of the mice and the concentrations of cortisol in the blood measured afterwards. Cortisol concentration in the blood increased after injection and stayed elevated for a few hours before returning to its usual low level. Physiologically effective amounts of CRF (corticotrophin releasing factor, a hypothalamic hormone) were then injected but no consequent increase in cortisol occurred. But the level of enkephalin in the blood did increase after CRF injection. Perplexed by this last result, the investigators removed pituitary glands from normal and abnormal mice for histological and biochemical analysis.
By all histological criteria, pituitary sections from the two kinds of mouse were indistinguishable.
Using a new technique to separate pituitary basophils from all other cells, the investigators were able to extract all the proteins contained in basophils and compare those present in normal and abnormal cells. To their great relief, there were only a few differences, one of them being the total absence of two particular normal proteins from the abnormal basophils. Thinking they had at least identified the CRF receptor, they sequenced the purified proteins but found nothing of much interest in either: neither transmembrane domains nor kinase substrate sites. Feeling somewhat depressed they mixed one of the pure proteins with a couple of other proteins they happened to have around, angiotensinogen and serum albumin, and examined the mixture after a while. They found that the angiotensinogen was now present as three different peptides, each larger than 25 amino acids, while the albumin now appeared as two large peptides. The other protein gave similar results but the fragments of angiotensinogen and albumin were of different sizes. At this point they got very excited, did a few more quick experiments, and rushed a manuscript to The Journal of Molecular Endocrinology.
If you had been part of the research team, what would you have concluded is the basis of the odd glucocorticoid and enkephalin responses in this strain of mouse?