Ontogeny of the in vitro growth hormone stimulatory effect of thyrotropin-releasing hormone in the rat.
The ontogenic changes in the somatotroph's responsiveness to TRH were examined in enzymatically dissociated rat pituitary cells in primary monolayer culture. Exposure to TRH (10(-8) M) caused a significant increase in GH release in cultured pituitary cells from rats ranging in age from -1 day (20 days of gestational age) to 90 days. The magnitude of the response, expressed as a percent increment above control rat GH (rGH) release, rose progressively until it reached a maximum of 209 +/- 5% (mean +/- SE) on postnatal day 12. Thereafter, the response declined to values ranging from 10-30% above control rGH release. In cultured adenohypophyseal cells of rats on postnatal day 12, the effect of TRH was dose related; the effective concentration range was 10(-10)-10(-7) M, with an EC50 of 2.5 +/- 0.6 X 10(-9) M. TRH (10(-8) M) potentiated the GH stimulatory effect of a submaximally effective concentration of human GH-releasing factor-40 (hGRF-40; 10(-9) M) in cultured pituitary cells of developing rats, aged -1 to 30 days, and that of (Bu)2cAMP (5 X 10(-4) M) in cultured pituitary cells of rats aged -1 to 45 days. The rGH response to the combined addition of TRH with either hGRF-40 or (Bu)2cAMP was up to 2 times greater (P less than 0.05) than the sum of the individual responses. When the interaction of TRH (10(-8) M) with multiple concentrations of hGRF-40 (10(-10), 10(-9), and 10(-8) M) was tested in cultured pituitary cells of 4- to 36-day-old rats at 4-day intervals, synergism was least at the lowest and greatest at the highest concentration of hGRF-40; synergistic interaction decreased progressively after 20 days of age to undetectable levels by 36 days. In cultured anterior pituitary cells of 12-day-old rats, maximally stimulatory TRH (10(-7) M) potentiated the GH stimulatory effects of both hGRF-40 and (Bu)2cAMP at concentrations at the EC50 value or greater, with synergism being most pronounced at maximally effective concentrations. Whereas the GH response to the combined addition of maximal hGRF-40 (10(-7) M) and (Bu)2cAMP (1.5 X 10(-3) M) was not greater than that to maximal hGRF alone, TRH potentiated the responses to both secretagogues whether added separately or combined.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013961:Thyroid Gland / Q000196:embryology / Q000254:growth & development*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D002121:Calcium Channel Blockers; D010446:Peptide Fragments; C036893:somatotropin releasing factor 40; D003035:Cobalt; D013973:Thyrotropin-Releasing Hormone; D003994:Bucladesine; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C018021:cobaltous chloride