THE MOLECULAR EVOLUTION OF PITUITARY HORMONES
Authors: WALLIS M. 
Published: January 2008

Summary1. The pituitary hormones can be divided into 4 families; within each the members are structurally related and have probably evolved from a common ancestor by a process of gene duplication and divergence.2. Recent structural studies have revealed much about the evolution of proteins. The roles of point mutation, gene duplication and partial gene duplication in molecular evolution have been highlighted, and the nature of the evolutionary forces involved has been extensively debated. The information available about the evolution of proteins in general provides a background for consideration of pituitary hormone evolution.3. The structure and function of the mammalian neurohypophysial hormones (oxytocin and vasopressin) has been studied in detail. Related (structurally similar) peptides have been found in the neurohypophyses of lower vertebrates and have been Characterized in many instances. Several schemes have been proposed for the evolution of these hormones.4. The vasopressins of the pig and its relatives show a genetic polymorphism. The roles of neurohypophysial hormones in lower vertebrates are very varied and not fully understood.5. The ACTHs and MSHs are members of a second family of pituitary hormones. They are polypeptides of moderate size. Studies on amino‐acid sequences have been carried out for ACTHs and MSHs from several mammals. α‐MSH is identical in all cases studied in detail, but β‐MSH and ACTH vary to some extent. There is considerable sequence homology between the hormones in this family ‐ indicating a common phylogenetic origin and several gene duplications.6. Dogfish MSH is the only non‐mammalian hormone of the ACTH‐MSH family to have been studied in detail. Two MSHs have been isolated from this species; both resemble the a‐MSH of mammals in amino‐acid sequence. ACTH‐like and MSH‐like hormones exist in many other vertebrate groups, but have not been characterized fully.7. Structure‐function relationships have been widely studied in the ACTH‐MSH family, and have some interesting evolutionary implications. Polymorphism of P‐MSHs is found in some mammals.8. A third family of protein hormones includes pituitary prolactin and growth hormone, and placental lactogen. These are proteins of moderate size which have been shown to be widely distributed among the vertebrates. Species specificity can be recognized with regard to biological, immunological and structural properties.9. Amino‐acid sequences have been determined for growth hormones and prolactins from several mammals. There is sequence homology between growth hormone and prolactin. Human placental lactogen closely resembles human growth hormone. A phylogenetic tree has been constructed for this protein family. Rates of evolution within the group are rather variable.10. The fourth family of pituitary hormones (FSH, LH, TSH and some related placental hormones) are all glycoproteins and have a subunit structure. Extensive sequence studies have been carried out on the hormones from some mammals, and show that there is considerable homology between the various subunits. The α‐subunits of human TSH, LH and HCG (and probably FSH) are very similar. The β‐subunits are different, but homologous. Evolution of this family clearly took place by a series of gene duplications followed by gene divergence. Schemes whereby this could have occurred have been discussed. Related hormones occur in lower vertebrates, but have not been fully characterized. Some lower vertebrates may possess only one gonado‐trophin.11. The pituitary hormones provide an interesting range of evolutionary problems, and are useful models for the study of molecular evolution. The evolutionary processes involved in their diversification have been discussed, with particular reference to the co‐evolution of hormones and their receptors. Neutral mutations and gene duplications may have played a role in providing co‐existing variation of hormones and receptors.12. A speculative model for the evolution of neurohypophysial hormones is proposed, as an example of how molecular evolution may have operated in this and other hormone groups.13. Homologies have been proposed between the various families of pituitary hormones, and between pituitary proteins and other entero‐secretory proteins. The pituitary protein hormones were probably elaborated from smaller molecules by a process of partial gene duplication.