Suppression of somatotroph function induced by growth hormone treatment in neonatal pigs.
The effect of recombinant porcine growth hormone (pGH) treatment on pituitary function was evaluated in young pigs. Piglets received intraperitoneal recombinant pGH implants (0.5 mg/d sustained release) or vehicle implants beginning at 3 d of age. Ten piglets were sacrificed at 4 and 6 wk of age (five piglets/treatment group) for the collection of pituitary glands, blood, and liver tissue. Blood samples also were drawn at 3 and 12 d of age. Serum concentrations of GH, prolactin (PRL), thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1) and IGF-2 were evaluated. Levels of IGF-1 and IGF-2 mRNA were determined in liver samples. Treatment with GH increased circulating levels of GH and IGF-1 (P < 0.01), but not PRL, TSH, or IGF-2. Hepatic IGF-1, but not IGF-2, mRNA levels were increased by pGH (P < 0.001). Cultured pituitary cells from each animal were challenged with 0.1, 1, and 10 nM GH-releasing hormone (GHRH); 2 nM 8-Br-cAMP; or 100 nM phorbol myristate acetate. The release of GH from cultured pituitary cells was stimulated by all secretagogues (P < 0.001). The secretion of GH, but not PRL or TSH, in culture was inhibited by previous in vivo GH treatment (P < 0.001). Similarly, cellular GH, but not PRL or TSH, content was lower in the GH-implant group (P = 0.005). Cell cultures from 6-wk-old piglets secreted more GH, but not PRL or TSH, than cultures from 4-wk-old piglets (P < 0.05). Likewise, cellular GH, but not PRL or TSH, content was greatest in cultures from 6-wk-old animals (P = 0.002). Piglet growth was not affected by exogenous GH treatment (P = 0.67). These results demonstrate that exogenous pGH treatment selectively down-regulates somatotroph function in young pigs.
Matteri
R L
RL
Animal Physiology Research Unit, United States Department of Agriculture, University of Missouri, Columbia 65211, USA.
Becker
B A
BA
Carroll
J A
JA
Buonomo
F C
FC
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002478:Cells, Cultured; D013006:Growth Hormone / Q000494:pharmacology* / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology*; D011388:Prolactin / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013972:Thyrotropin / Q000097:blood
D012333:RNA, Messenger; D011994:Recombinant Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate