Some Unexplained Metabolic Actions of Pituitary Hormones with a Unifying Hypothesis Concerning their Significance †‡

The elucidation of the nature and actions of the adenohypophyseal hormones has been a challenging problem which has been yielding to attack only very slowly. It has been recognized for some time that there are several adenohypophyseal hormones at least one of which, growth hormone or somatotropin, has general systemic metabolic actions."7 All the others, corticotropin, thyrotropin, follicle-stimulating hormone, luteinizing hormone and prolectin or luteotropin, appear to have their actions primarily if not solely on specific target glands. Despite substantial progress in the morphological localization of the pituitary hormones and their chemical purification, we still know very little either about the exact chemical nature of these hormones as they are formed and exist in the gland, or about their properties as they are secreted into the bloodstream. At one time it was believed that all the pituitary hormones were protein in nature but in recent years it has been established that biological activity of at least one-ACTH-may be associated with a polypeptide molecule which is much smaller than was suspected.' However, it must be borne in mind that the mere fact that a polypeptide has biological activity does not necessarily imply that this is the molecular form in which the hormone is stored in the gland or is secreted. Nor can we even be certain that the biological activities reported for the purified hormones are necessarily those of the naturally secreted hormones. It must be appreciated that we are dealing with properties of very complex molecules and that the multiple biological activities of the different pituitary hormones probably depend on specific molecular configurations of peptide chains. The chemist might inadvertently alter these in his search for purity, thereby eliminating some