Sequences of Pituitary and Placental Lactogenic and Growth Hormones: Evolution from a Primordial Peptide by Gene Reduplication

Abstract

Human placental lactogen has been found to resemble human pituitary growth hormone very closely in amino acid sequence, about 80% of the residues examined being identical in the two molecules when a revised sequence for growth hormone is used as the basis for comparison. The structural features responsible for the differing biological potency of the two hormones may therefore reside in rather limited regions of primary structure. The observation of internal sequence homologies within the pituitary growth hormone and prolactin and the placental lactogen molecules suggests that these polypeptide hormones may have evolved by genetic reduplication from a smaller common ancestral peptide. This finding directs further attention to subfragments of these molecules as possible possessors of intrinsic somatotrophic and lactogenic activity.Previous studies on pituitary growth hormone and prolactin, and on placental lactogen, have demonstrated a close structural similarity within this group of hormones, and thus provided a basis for their shared biological and immunological properties (1-6). However, complete amino acid sequences have been reported so far only for human growth hormone (1) (growth hormone) and ovine prolactin (3) (prolactin), and detailed intra-species comparisons of structure have not been possible. Recently, we have extended earlier structural studies (2, 5) on human placental lactogen (lactogen) and have determined much of its amino acid sequence. In the course of this work it was noted that discrepancies existed between the amino acid sequence of growth hormone as previously reported by Li and coworkers (1), and that which would have been predicted by homology with the structure of lactogen as determined in our laboratory. This led us to postulate an error in the previous growth hormone sequence, and to undertake a reinvestigation of its primary structure. Our results (7) showed that the previous aminoterminal structure of growth hormone was in fact incorrect, and that a sequence of 15 amino acids containing the single tryptophan of growth hormone, assigned by Li and coworkers to positions 17-31, must reside elsewhere in the molecule, most probably occupying positions 77-91. Our more recent investigations (manuscript in preparation) of the growth-hormone sequence have confirmed that this is indeed the correct location for the tryptophan sequence, and have also demonstrated the presence of the proposed (7) "missing" dipeptide sequence (Leu-Arg) at positions 92 and 93. Work in progress strongly suggests the existence of several further errors in the previous sequence for growth hormone. One of these involves residues 130-132, which we find to be Gly-Ser-Pro rather than Pro-Ser-Gly (see Fig. 4).The present report describes sequence studies on lactogen that demonstrate an extremely close homology with the revised growth hormone structure (7). More surprisingly, we also observed unequivocal internal sequence homology between four different regions of the lactogen structure. Examination of the revised ...

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

“…PRL is a polypeptide hormone, which is secreted in a pulsatile fashion and is structurally related to GH and human placental lactogen (hPL) (Niall et al, 1971). PRL release follows a circadian rhythm, with increased secretion in the early evening hours (Sassin et al, 1972;Waldstreicher et al, 1996).…”

The primary structure of bovine prolactin

“…The sequences of growth hormones and prolactins show some homology [13,17,19,20] and indicate that the two hormones can be considered members of a single family of protein hormones. This is clear when the sequences of bovine growth hormone [ 111 and bovine prolactin ( fig.…”

“…Prolactin is also homologous with human placental lactogen [ 13,17,19,20] but the degree of homology between these two lactogenic hormones is no greater than that between prolactin and growth hormone, while human placental lactogen and human growth hormone show a high degree of homology.…”

Human Chorionic Somatomamotraophin and Its Clinical Significance

“…Subsequent investigation of their amino-acid composition showed close similarities (Friesen, 1965;Catt et al, 1967;Sherwood, 1967). Recently Niall et al (1971) have succeeded in establishing much of the amino-acid sequence of HCS and showed that there is an identity of more than 80% between the molecules of HCS and HGH. Sherwood et al (1971) and Li et al (1971) have achieved a complete identification of the structure of HCS which they find to contain 190 amino-acid residues, the same number as in HGH, and also found 85% of residues to be identically placed in the two molecules.…”