Serum Concentrations of 20K Human Growth Hormone in Normal Adults and Patients with Various Endocrine Disorders

Abstract

Abstract.The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary.The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118 ± 178 pg/mL (N = 282) in normal women, significantly higher than in normal men (64± 170 pg/mL, N=226).However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 ±2.6%, N= 176) and women (6.3±2.1 0, N=263).No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P<0.001) higher in patients with active acromegaly (9.2±2.2%, N = 33) and in patients with anorexia nervosa (9.0± 1.9, N = 8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH.The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH. THERE are several isoforms of human growth hormone (27K, 22K, 20K, and 19K hGH, and 5K hGH fragment) in both pituitary and serum [1] . The major species is 22K hGH, and the second most abundant isoform is 20K hGH, which lacks 32-46 residues of 22K hGH. The 20K hGH is produced by alternative splicing of 22K hGH mRNA [2],and this

Growth hormone: isoforms, clinical aspects and assays interference

“…Females usually have higher secretion rates, higher interpeak levels and more erratic secretion patterns of this isoform than males [ 34 ]. The 20 K-GH isoform has been reported to be higher in females than males, although the ratio of 20- to 22 K-GH usually does not differ between sexes [ 35 , 36 ]. 22 K-GH secretion patterns also change with age.…”

“…Some studies reported no influence of age, pubertal stage and sex on the 20 K/22 K-GH ratio in normal and GH deficient children and adults. There was also no change in 24-h GH secretion pattern after arginine and hypoglycemia stimulation tests [ 17 , 35 , 36 ]. Another group studied normal children after a different stimulation test (GHRH).…”

“…Little data exist regarding GH isoforms in other conditions. One study showed that anorexia was associated with a higher abundance of the 20 K-GH isoform (20 K/20 K-GH + 22 K-GH), but there was no difference in hypothyroidism, hyperthyroidism and non-insulin dependent diabetes [ 35 ].…”

Genetic Engineering and Biotechnology of Growth Hormones

“…Its smaller size is due to elimination of the first 45 nucleotides of the third exon of the mRNA and of the amino acids that correspond to positions 32-46 of the hormone, producing a protein with 176 amino acid residues (4). This isoform comprises approximately 10% of all the GH produced in the hypophysis and although it has not been shown to be the etiological agent of any known disease, it is known that its levels are significantly higher in patients with active acromegaly and in those with anorexia nervosa (5).…”