A betaLPH precursor model: recent developments concerning morphine-like substances.

Abstract

In summary, the pituitary glands from at least four species contain betaLPH and and beta endorphins. We have shown that in slices of whole pituitaries betaLPH is actively biosynthesized and transformed into gammaLPH, thus releasing the COOH-terminus portion 61--91, which is now known as beta-endorphin. Newly radioactive biosynthesized beta-endorphin has been clearly and definitely identified. The release of betaMSH and possibly of beta-endorphin could well be under the control of CRF. The intermediate lobe of the pituitary seems to be the tissue that contains most of betaLPH and beta-endorphin, although these are also present in the anterior lobe. We have recently demonstrated its presence in human glands and the structure is completely identical to the COOH-fragment 61--91 of human betaLPH. Thus far, these morphine-like peptides seem not to cross the blood-brain barrier in rats; it is conceivable (neurophysiologists will need to look into it) that an upward circulatory process could bring beta-endorphin into the brain where it is concentrated in different regions as either native or degraded products both of which have similar activities. Until somebody shows that betaLPH and beta-endorphin are actively biosynthesized in other tissues, one can only assume that the pituitary gland is the primary source of the endogenous opiate substance(s) and that betaLPH is its or their biologic precursor. We have worked on the proposed biosynthetic model for many years and we are continuing because all of the experiments, except one from another laboratory, 38indicate that we are moving slowly toward its confirmation. Thus far, there is no reason to believe the contrary, and we are following in some ways Konrad Lorenz's maxim, which appeared in his book Die Acht Todsunden Der Zivilisierten Menscheit, published in French in 1973: "Une bonne hypothése de travail gagne en vraisemblance lorsque, au cours de longues années de recherches, nulle donnée n'est venue la contredire." The major conclusion of our most recent studies on the biosynthesis of betaLPH and its related peptides have led us to the first in vitro biosynthesis of an endogenous morphine-like substance. This constitutes a major step in the comprehension of this exciting new field.