Arginine vasopressin in extracts of bovine pituitary.

Gitelman et al. (1) suggest the natural occurrence in the bovine posterior pituitary of two different N-terminal "hormonogen" forms of arginine vasopressin. Since both hormonogens were found to be natriuretic, there is an implication that they may be related to "natriuretic hormone." This stimulates not so much comment as questions, since were this concept shown to be valid much of what we thought we knew about these hormones would have to be modified. 1) The original isolation of vasopressin and oxytocin from the pituitary by du Vigneaud failed to find such hormonogen forms, but of course the original work was searching for maximum pressor and antidiuretic activities, not natriuretic. This same statement applies to many other laboratories about the world carrying out the same work. In 1974, we tried to isolate peptides using natriuresis as a criterion, also using freeze-dried posterior pituitaries as a starting material. The most active fractions contained two chromatographically clean spots on thin-layer chromatography; these spots were identified clearly as the nonapeptide vasopressin molecule and adrenocorticotropic hormone (1-13) with a nonacetylated N-terminus (2), again providing no evidence for the presence of vasopressin hormonogens. Could Gitelman et al. present evidence that what they were sequencing was in fact two pure substances? 2) Gitelman et al. comment that most oligopeptide hormones appear to be biosynthesized as larger molecules, but this is supposed to occur in the hypothalamus, not in the posterior pituitary. In fact, had the authors carried out their isolation from the hypothalamus, the results would be more convincing. As far as we know, once vasopressin is produced in the hypothalamus, it is only transported for storage to the posterior pituitary, not as a nonapeptide alone but in noncovalent binding to "carrier proteins"-neurophysins. It is well known, however, that vasopressin-neurophysin binding requires that the Na-NH2 group be immediately contiguous to 2-Tyr in order for binding to occur (3 been shown experimentall sertion of one or more residL Tyr and the Na-NH2 grou binding, that is, the hormono elman et al. would not bin( suggesting that vasopressin i; sized in the posterior pituit wise the hormonogens coul reached that organ. 3) Genetic coding being there should be in a given spe a sequence of a prohormone for the ""final" nonapeptic Why, then, are there two fi prohormone? 4) Such N-terminal "horm4 tensions of vasopressin (mor all) were synthesized as long (4) with one to three added tached to I-Cys. Provided th idues are cleavable by amin (that is, are alkyl, aromatic, not basic, acidic, or D-isome all natriuretic [for example, as the parent hormone is. H lates to a "natriuretic horm ever, is still not clear.