The Ontogenesis of Human Fetal Hormones. I. Growth Hormone and Insulin

The content and concentration of immunoreactive growth hormone (GH) were measured in 117 human fetal pituitary glands from 68 days of gestation to term and in the pituitary glands of 20 children 1 month to 9 yr of age. Physicochemical and immunochemical properties of GH of fetal pituitary glands and GH from adult pituitary glands were indistinguishable by disc gel electrophoresis, immunoelectrophoresis, starch gel electrophoresis, and radioimmunoassay techniques. In the fetal pituitary gland, the GH content rose from mean levels of 0.44+/-0.2 mug at 10-14 wk of gestation, to 9.21+/-2.31 mug at 15-19 wk, to 59.38+/-11.08 mug at 20-24 wk, to 225.93+/-40.49 mug at 25-29 wk, to 577.67+/-90 mug at 30-34 wk, and to 675.17+/-112.33 mug at 35-40 wk. There was a significant positive correlation between growth hormone content of the pituitary and gestational age, crown-rump length, and the weight of the pituitary gland. The content and concentration (micrograms/milligram) of human growth hormone (HGH) in the fetal pituitary showed significant increments (P < 0.001) for each 4 wk period of gestation until 35 wk. Further increases in the HGH content were noted in pituitaries of children aged 1-9 yr (range of 832 to 11.211 mug). Immunoreactive GH was detected in fetal serum at a concentration of 14.5 ng/ml as early as 70 days gestation, the youngest fetus assayed. At 10-14 wk, the mean concentration of serum growth hormone was 65.2+/-7.6 ng/ml; at 15-19 wk 114.9+/-12.5 ng/ml; at 20-24 wk 119.3+/-19.8 ng/ml; at 25-29 wk 72.0+/-11.5 ng/ml; and 33.5+/-4.2 ng/ml at term. A significant negative correlation of serum growth hormone with advancing gestational age after 20-24 wk was observed (P < 0.001). In 17 fetuses paired serum and pituitary samples were assayed; no significant correlation between the concentration of serum GH and the pituitary content or concentration of GH was demonstrable. The serum concentration of chorionic somatomammotropin (HCS) in the fetus was unrelated to gestational age. Insulin (1-30 muU/ml) was detected in 42 of 46 fetal sera assayed. These data suggest that the appearance and development of the secretory capacity for GH by the human fetal pituitary gland coincides with developmental changes in the portal system and hypothalamus. Maturation of inhibitory central nervous system control mechanisms for secretion of GH may not occur until infancy.