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Title: Insulin-like growth factor-I feedback regulation of growth hormone and luteinizing hormone secretion in the pig: Evidence for a pituitary site of action

Author
item Barb, Claude
item Hausman, Gary

Submitted to: Animal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2008
Publication Date: 6/1/2009
Citation: Barb, C.R., Hausman, G.J. 2009. Insulin-like growth factor-I feedback regulation of growth hormone and luteinizing hormone secretion in the pig: Evidence for a pituitary site of action. Animal. v.3(6) p. 844-849.

Interpretive Summary: Understanding the mechanisms that regulate growth hormone (GH) secretion, necessary for stimulation of growth, is of great relevance in the rapidly growing pig. Growth hormone releasing hormone (GHRH), a brain hormone, stimulates GH secretion from the pituitary gland. Growth studies demonstrated that GH secretion decreased and insulin-like growth factor-I (IGF-I, a hormone necessary for growth) increased with age while pituitary expression of GH, IGF-I receptor (R) or GHRHR was not age dependent. Administration of IGF-I into the lateral ventricle of the brain failed to effect GH secretion. However, IGF-I, modulation of GH secretion from the pituitary cells in culture is age dependent and occurred independent of any influence from the brain in the growing pig. This is the first report to confirm that decreased GH secretion in response to GHRH during development may be explained, in part, by increased sensitivity to IGF-I. This information is necessary to develop novel methods to promote maximal growth during development in the pig.

Technical Abstract: The ontogeny of IGF-I modulation of GH secretion from the anterior pituitary was studied. In EXP I, serial blood samples were collected from gilts at 90, 150 and 205 days of age, and 24 hr later anterior pituitary glands were collected for expression analysis of GH and pituitary-specific transcription factor -1 (Pit-1), GH releasing hormone receptor (GHRHR), IGF-I receptor (IGF-IR), and somatostatin (SS) receptor (SSR)-1, -2, -5. Serum was analyzed for GH and IGF-I. In EXP II, prepuberal gilts received intracerebroventricular (ICV) injections of saline (n = 4), 25µg (n = 4) or 75µg (n = 4) IGF-I and blood samples were collected for GH. In EXP III, anterior pituitary cells in culture collected from 110 day old fetuses, 2-, 4- and 6- month old gilts were challenged with 0.1, 10 or 1000 nM GHRH, or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 1000 nM GHRH. Secreted GH was measured at 4 h after treatment. In EXP I, serum GH concentration decline and IGF-I concentration increased with age while Pit-1, GH, GHRHR, IGF-IR, SSR1, SSR2 and SSR5 gene expression was unchanged. In EXP II, GH levels were unaffected by ICV IGF-I. In EXP III, all doses of GHRH increased GH in fetal pituitary cultures whereas there was an age dependent decrease in GH reponse to GHRH. IGF-I increased basal GH secretion only in fetal and 6 month old gilt pituitary cultures. IGF-I enhanced GH response to GHRH only from fetal and 2 month old pituitary cell cultures whereas this response was suppressed in pituitary cultures from 6-monthold pigs. These results demonstrate that GHRH and IGF-I modulation of GH secretion is age dependent and occurred independent of hypothalamic input.