Transcriptional regulation of pituitary synthesis and secretion of growth hormone in growing wethers and the influence of zeranol on these mechanisms

This experiment evaluated relationships between pituitary messenger RNA lev els of the transcription factor Pit-1, the growth hormone releasing-hormone receptor (GHRHR), and synthesis and secretion of GH in growing wethers. Th e experiment also evaluated the influence of the estrogenic compound, zeran ol, on these relationships. Seventy wethers that were 9.5 +/- 1 day of age were randomly assigned to a control group or to one of three zeranol treatm ent groups that were implanted (12 mg, Ralgro) at 0, 45, and (or) 90 days o f age. Twenty-eight days after implantation (i.e., Days 28, 73, 118) and on Day 135, sera were collected serially from wethers (n greater than or equa l to 5) from each group and then their pituitary was collected. As wethers gained weight with age, the pituitary increased in size and so did the rela tive message levels of Pit-1 and GH (effect of time, P < 0.01). However, as wethers reached 135 days of age, serum concentrations of GH had declined w hile concentrations of IGF-I had increased (linear contrast, P < 0.01). Add itionally, zeranol increased serum concentrations of GH and IGF-I and this effect on GH appeared to be a consequence of increased pulse amplitude, par ticularly at 73 and 118 days of age (treatment x time, P less than or equal to 0.074). This result could have been due to increased pituitary expressi on of GH (treatment, P < 0.08). Zeranol appeared to modulate pituitary expr ession of transcripts containing exon 3 of Pit-1 (treatment, P < 0.01) and GHRHR (treatment x time, P = 0.056), however, pituitary message levels of P it-1 and GHRHR were not positively correlated to pituitary expression of GH mRNA or serum concentrations of GH. (C) 2000 Elsevier Science Inc. All rig hts reserved.