RT Journal Article
SR Electronic
T1 Central Administration of a Growth Hormone (GH) Receptor mRNA Antisense Increases GH Pulsatility and Decreases Hypothalamic Somatostatin Expression in Rats
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8140
OP 8148
DO 10.1523/JNEUROSCI.16-24-08140.1996
VO 16
IS 24
A1 Elisabeth Pellegrini
A1 Marie Thérèse Bluet-Pajot
A1 Françoise Mounier
A1 Pamela Bennett
A1 Claude Kordon
A1 Jacques Epelbaum
YR 1996
UL http://www.jneurosci.org/content/16/24/8140.abstract
AB To test the hypothesis of the involvement of centrally expressed rat growth hormone receptors (rGH-R) in the ultradian rhythmicity of pituitary GH secretion, adult male rats were submitted to a 60 hr intracerebroventricular infusion of an antisense (AS) oligodeoxynucleotide (ODN) complementary to the sequence of rGH-R mRNA. Eight hour (10 A.M.–6 P.M.) GH secretory profiles, obtained from freely moving male rats infused with 2.0 nmol/hr of rGH-R AS, revealed a marked increase in GH peak amplitude (150 ± 12 vs 101 ± 10 ng/ml), trough levels (16.2 ± 3.0 vs 5.4 ± 1.4 ng/ml), and number of peaks (2.9 ± 0.3 vs 1.8 ± 0.2). No change was observed in rats treated with an ODN complementary to the prolactin receptor mRNA sequence (2.0 nmol/hr). Infusion of increasing ODN concentrations resulted in a dose-dependent stimulation of GH release. In parallel, somatogenic binding sites in the choroid plexus were decreased by 40%, and levels of rGH-R mRNA were increased in the periventricular nucleus (PeV) but unchanged in the arcuate nucleus (ARC). Levels of somatostatin mRNA, in the PeV but not in the ARC, were lowered by the treatment. Levels of GH-releasing hormone mRNA in the ARC were not affected. These data suggest that GH negative feedback results from a direct effect on central GH receptors and a subsequent activation of hypophysiotropic somatostatin neurons located in the anterior periventricular hypothalamus.