title: Growth hormone regulation in primary fetal and neonatal rat pituitary cell cultures: the role of thyroid hormone.
abstract: GH is first detectable in the fetal rat pituitary between gestational days 18 and 19. The reasons for the GH surge soon after birth and subsequent postnatal decline to adult levels remain unclear. We therefore determined whether GH gene regulation in the developing pituitary could be distinguished from adult rat somatotroph function. In primary cultures of fetal and neonatal rat pituitary cells, GH secretion was detected by the 20th gestational day. These cells were stimulated by GH-releasing hormone (GHRH), but not by T3 or the morphogen retinoic acid. The stimulatory effect of T3 (0.25 mM) on GH secretion was detected only on the 2nd neonatal day and was similar to that seen in mature rat pituitary cell cultures. GHRH (10 nM) treatment for 24 h caused a 5-fold induction of GH secretion in pituitary cells derived from 2-, 5-, and 12-day-old neonatal rats. The presence or absence of T3 in the culture medium did not alter the response to GHRH. In contrast, only 2-fold induction of GH was observed in adult male pituitary cells during the same time course. Insulin-like growth factor-I (IGF-I; 6.5 nM), the peripheral target hormone for GH, resulted in a modest (20%) attenuation of GH secretion from pituitary cells derived from 20-day-old fetuses. IGF-I, however, produced a 70% reduction in GH levels in adult male pituitary cells grown under similar conditions. The effects of IGF-I on adult pituitary cells grown in T3-depleted medium were blunted. Addition of T3 partially restored the responsiveness of these cells to IGF-I. The results suggest that the high circulating GH levels in the fetal and neonatal rat may be secondary to relative insensitivity of the immature somatotroph to the inhibitory actions of IGF-I in addition to enhanced responsiveness to GHRH compared with the adult rat pituitary. Relative thyroid hormone deficiency in the immature rat may be contributory to this early transient state of pituitary IGF-I resistance.
authors.affiliation: Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center-University of California School of Medicine, Los Angeles 90048.
authors.forename: S
authors.initials: S
authors.lastname: Ezzat
authors.forename: D
authors.initials: D
authors.lastname: Laks
authors.forename: J
authors.initials: J
authors.lastname: Oster
authors.forename: S
authors.initials: S
authors.lastname: Melmed
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D013963:Thyroid Hormones; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone