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Development of hypothalamic control of growth hormone secretion in the rat
Insights
Hypothalamic control of growth hormone (GH) in developing rats involves a peptidergic GH-releasing factor and pituitary insensitivity to somatostatin. These factors, along with GH storage dynamics, maintain high GH levels during prenatal and early postnatal stages.
Area of Science:
- Endocrinology
- Developmental Biology
- Neuroendocrinology
Background:
- Growth hormone (GH) secretion is tightly regulated by the hypothalamus.
- Understanding the developmental trajectory of this control is crucial for deciphering neonatal physiology.
Purpose of the Study:
- To investigate the development of hypothalamic regulation of GH secretion in rats during late prenatal and early postnatal periods.
- To elucidate the roles of hypothalamic factors and somatostatin in modulating GH release during development.
Main Methods:
- Static incubation system for rat pituitaries at various developmental stages (prenatal days 18-21, postnatal days 1, 5, 8).
- Measurement of basal and stimulated GH secretion using thyrotropin-releasing hormone (TRH) and hypothalamic extracts.
- Assessment of somatostatin's inhibitory effects and cerebral cortical extract's influence on GH release.
Main Results:
- Basal GH secretion increased from prenatal day 18 to postnatal day 1, then declined. Pituitary GH content rose steadily.
- TRH stimulated GH secretion from prenatal day 21 onwards. Hypothalamic extracts from fetuses, neonates, and adults stimulated GH release.
- Pituitary insensitivity to somatostatin was observed until postnatal day 5, though high concentrations inhibited earlier. Somatostatin attenuated hypothalamic extract-induced GH release.
Conclusions:
- High circulating GH levels in late prenatal and early neonatal rats are maintained by a peptidergic GH-releasing factor and relative pituitary resistance to somatostatin.
- Developmental changes in GH storage and release pools also contribute to regulating GH secretion.
- The findings highlight a complex interplay of factors governing GH regulation during a critical developmental window.
Abstract:
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.