Receptors for somatotropin (growth hormone) and prolactin.

Pituitary somatotropin (growth hormone) and prolactin are two related protein hormones produced by the pituitary gland. Both contain single polypeptide chains of 190-200 amino acid residues (Wallis, 1978). In mammals, prolactin acts primarily on the mammary glands, promoting mammary growth and lactation; in many species it also has direct effects on the gonads and possibly other organs (Horrobin, 1978). Somatotropin promotes overall somatic growth, stimulating growth of a wide variety of tissues. Many of its effects are mediated by a family of insulin-like peptides, the somatomedins, which are produced in the liver and possibly other organs; precisely which of the effects of somatotropin are direct and which somatomedin-mediated remains poorly understood. Somatotropin also has actions on carbohydrate and lipid metabolism, but how these relate to its actions on growth promotion is unclear. Somatotropins (and prolactins) from different species differ considerably in amino acid sequence and immunological and biological activity (Wallis, 1975, 19800). This species variation is very non-uniform, probably as a consequence of variable rates of evolution within the protein family (Wallis, 1981). For example, the sequences of rat, pig, horse and whale somatotropins are very similar (though these species belong to four separate mammalian orders), but all differ considerably (at about 35% of all amino acid residues) from human somatotropin. In the case of the prolactins, the rat hormone is markedly different from the hormone from most other mammalian species. These marked structural variations are accompanied by differences in biological activity. For example, non-primate somatotropins are inactive in man (hence the need for human somatotropin for clinical treatment of hypopituitary dwarfism) and, unlike somatotropins from most non-primate mammals, the human hormone has marked lactogenic activity; on the other hand, most mammalian somatotropins appear to be equally effective in the rat. The full biological consequences of the species specificity of somatotropin and prolactin have not been established, but it is clear (as will be emphasized below) that they must be considered when hormone-receptor interactions are being considered. A further aspect of the chemistry of somatotropin and prolactin of relevance to hormone-receptor interactions concerns the possibility that the well-characterized stored forms of the hormones are converted into more active forms at some stage during secretion or in the circulation. This possibility has been most extensively considered for somatotropin. Modified forms of this hormone with increased or altered activity (including somatomedin-like activity) have been reported, but their full physiological significance and importance has yet to be established (reviewed by Wallis, 1978).