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Ontogeny of the response to growth hormone-releasing factor
Insights
Rat fetal pituitary cells respond to growth hormone-releasing factor (GRF) in late gestation. This suggests GRF regulates growth hormone (GH) levels during the perinatal period, indicating developmental maturation.
Area of Science:
- Endocrinology
- Developmental Biology
- Reproductive Science
Background:
- Growth hormone (GH) regulation is crucial for development.
- The role of growth hormone-releasing factor (GRF) in fetal pituitary function is not fully understood.
- Intracellular GH processing undergoes maturation during gestation.
Purpose of the Study:
- To investigate the responsiveness of fetal, neonatal, and adult rat pituitary cells to GRF.
- To determine the developmental stage at which pituitary cells become sensitive to GRF.
- To explore the role of GRF in regulating GH secretion during the perinatal period.
Main Methods:
- Primary cell cultures were established from rat pituitaries at various gestational ages (days 18, 19, 21), birth (day 0), and postnatal day 1.
- Cells were stimulated with varying concentrations of rat GRF and forskolin (adenylate cyclase activator).
- GH secretion was quantified using established assays.
Main Results:
- Pituitary cells from fetuses at days 19 and 21, neonates, and adult rats exhibited dose-dependent GH release in response to GRF.
- Cells from day 18 fetuses showed a blunted response to GRF and forskolin compared to later stages.
- Fetal pituitary cells at days 18-19 released significantly more GH (up to 40%) compared to day 21 or neonatal cells (5-10%), suggesting maturational changes in GH processing.
Conclusions:
- Rat fetal pituitary is responsive to GRF in late gestation (days 19-21).
- GRF likely plays a role in regulating GH secretion during the perinatal period.
- Significant maturation of intracellular GH processing occurs late in gestation.
Abstract:
Primary cell cultures were prepared from fetal, neonatal and adult rat pituitaries and evaluated for their ability to secrete growth hormone (GH) in response to growth hormone-releasing factor (GRF). Pituitary cells prepared from fetuses at days 19 and 21 of gestation, neonatal animals at the day of birth (day 0) or the following day (day 1) and peripubertal male rats showed full dose response curves to GRF with maximal GH release when stimulated with 1 X 10(-10) M rat GRF. At this concentration of GRF, the amount of GH released was not different from that elicited by activation of adenylate cyclase with 1 X 10(-5) M forskolin. In contradistinction, a preparation of cells from fetuses at day 18 of gestation did not show the same release of GH when challenged with 1 X 10(-10) M GRF and forskolin (0.057 +/- 0.001, compared to 0.076 +/- 0.003 micrograms/10(5) cells per 4.5 h), although the cells clearly responded to both secretagogues (basal levels of GH, 0.029 +/- 0.002 micrograms/10(5) cells per 4.5 h). While cells prepared from fetuses at day 21 of gestation or from animals after birth released 5-10% of their total cellular GH content, those prepared from 18- and 19-day fetuses released as much as 40% of their total GH suggesting there is a maturation of intracellular GH processing that occurs late in gestation. The results show that, in late pregnancy, the rat fetal pituitary is highly responsive to growth hormone-releasing factor and suggest that this peptide participates in regulating GH levels during the perinatal period.