Development of hypothalamic control of growth hormone secretion in the rat.

The development of hypothalamic control of GH in the late prenatal and early postnatal periods in the rat was studied by employing a static system for the incubation of pituitaries. The basal secretion of GH into the medium after a 3-h incubation period showed a gradual increase from day 18 prenatally to day 1 postnatally. This was followed by a gradual decline in GH release on postnatal days 5 and 8. There was a sustained rise in the total pituitary GH content from prenatal day 18 to postnatal day 8. The percentage of the total GH that was released into the medium was high from fetal pituitaries and lower from neonatal pituitaries. TRH (100 ng/ml) stimulated GH secretion starting on prenatal day 21. This TRH effect persisted through day 8 postnatally. Hypothalamic extracts from fetuses and neonates stimulated the secretion of GH when coincubated with pituitaries of the same age and with adult male rat pituitaries. Similarly, adult male rat hypothalamic extract stimulated the secretion of GH from pituitaries of 1-day-old neonates. Pronase treatment of neonatal hypothalamic extract completely abolished its stimulatory effect on GH release. Incubation of 1-day postnatal pituitaries with cerebral cortical extract obtained from neonates of the same age did not alter the secretion of GH; however, cerebral cortical extract from adult males did cause a significant stimulation of GH release from the neonatal pituitaries. Somatostatin (100 ng/ml) failed to inhibit GH release by pituitaries until day 5 postnatally, but a 10-fold increase in the concentration of somatostatin significantly inhibited GH secretion from pituitaries of rats as early as day 21 prenatally. Coincubation of hypothalamic extract with the high concentration of somatostatin significantly attenuated the effect of the extract in stimulating GH release from pituitaries of 1-day-old rats. The results suggest that the high circulating levels of GH during the late prenatal and early neonatal periods are maintained by a combination of factors including the release of a hypothalamic peptidergic GH-releasing factor, the relative insensitivity of the pituitary to somatostatin, and changes in the relative size of storage vs. releasable pools of GH during development.