Growth hormone isoforms in newborns and postpartum women

Abstract

The neonatal and postpartum periods are characterized by alterations in pituitary GH secretion. We have investigated the proportion of circulating non-22 kDa GH isoforms in newborns, in women within the early postpartum phase (just after the disappearance of placental GH from the maternal circulation) and in women during late postpartum (during the somatotroph recovery phase). We studied 10 newborns (7 males; 3 females; median postnatal age, 45 h), who had been admitted because of polycythaemia, 10 women in the early postpartum phase (median, 48 h after delivery; range, 42-54 h), 18 women in the late postpartum phase (median, 10 weeks after delivery; range, 3-25 weeks) and 9 healthy non-pregnant women. The proportion of non-22 kDa GH isoforms was determined by the 22 kDa GH exclusion assay, which is based on immunomagnetic extraction of 22 kDa GH from serum, and quantitation of non-22 kDa GH isoforms using a polyclonal GH assay. In newborns, non-22 kDa GH isoforms were measured in two arterial blood samples obtained with a 5-6 h interval. In the other groups, serum samples were obtained 40 min after an i.v. bolus administration of the GH secretagogue, GH releasing peptide-1 (GHRP-1).In newborns, the median proportion of non-22 kDa GH isoforms was 10% (range, 7.2-19.4%) and the values were similar in samples collected at different times. In early postpartum women, total GH levels after GHRP-1 were lower and the proportion of non-22 kDa GH isoforms was higher compared with the values in non-pregnant and late-postpartum women. In late postpartum, there was a partial recovery of GH response to GHRP-1, as shown by an increment in total GH levels, which was associated with a decrease in the fraction of non-22 kDa GH isoforms.In conclusion, we found that (i) the proportion of non-22 kDa GH isoforms in the newborn is comparable to that in the adult (non-pregnant women), (ii) in early postpartum, the non-22 kDa fraction is high within the small pool of readily releasable GH, (iii) in late postpartum, recovery of pituitary GH responsiveness is associated with a relative decrease in the release of non-22 kDa GH isoforms.

Circulating non-22 kDa growth hormone isoforms after a repeated GHRH stimulus in normal subjects

“…By contrast, an interesting finding was that the proportion of non-22 kDa isoforms increased after the second GHRH stimulus in the ''non-responders'' when the GH secretion is diminished, with a clear negative correlation between total GH Peak-2 and the proportion of non-22 kDa isoforms. Following previous studies [6,29] an increase in the proportion of non-22 kDa hGH isoforms after a hGH stimulation test could be explained by: (a) the lower clearance of non-22 kDa isoforms or (b) a lack of function recovery of somatotroph cells after the first stimulus in this group.…”

“…In the GHEA, monomeric and dimeric 22 kDa GH molecules are extracted from serum using a specific anti-22 kDa GH antibody and paramagnetic beads, and the levels of non-22 kDa GH isoforms, including 20 kDa GH and other immunoreactive isoforms, fragments and oligomers of GH, are quantified [3]. The GHEA has been validated in different physiological and pathological conditions, bringing additional information on GH immunoreactivity in serum [6][7][8].…”

Measurement of human growth hormone by immunoassays: Current status, unsolved problems and clinical consequences

“…Not relevant to clinical routine diagnostics, but helpful for research applications, are various GH assays designed to exclusively or preferentially measure individual GH isoforms. Such assays exist for the measurement of the 20 kD isoform [36,37], for placental GH or GH-V [38], for the whole spectrum of ''non-22 kD" isoforms [39] and for the determination of the relative abundance of the 22 kD isoform [40].…”

Growth hormone assays: current methodologies and their limitations

“…However, specific assays have been developed to recognize primarily or only specific isoforms. Methods are available for the measurement of the 20 kD isoform [41], for placental GH or GH-V [42] and for the whole spectrum of ''non-22 kD'' isoforms [43]. These assays, however, at present are mainly used for basic research and have no routine clinical applications.…”