In this study, the spontaneous dwarf @entity35 (SDR) has been used to examine @entity11523 production and action in the selective absence of endogenous @entity11249 . This dwarf model is unique in that @entity11249 is not produced because of a point mutation in the @entity11249 gene. However, other pituitary hormones are not obviously compromised. Examination of the hypothalamic pituitary-axis of SDRs revealed that @entity11523 messenger RNA (mRNA) levels were increased, whereas @entity1943 (SS) and @entity10969 (NPY) mRNA levels were decreased, compared with age- and sex-matched normal controls, as determined by Northern blot analysis (n = 5 animals/group; P < 0.05). The elevated levels of @entity11523 mRNA in the SDR hypothalamus were accompanied by a 56% increase in pituitary @entity56965 ( @entity56965 ) mRNA, as determined by RT-PCR (P < 0.05). To investigate whether the up-regulation of @entity56965 mRNA resulted in an increase in @entity56965 function, SDR and control pituitary cell cultures were challenged with @entity11523 (0.001-10 nM; 15 min), and intracellular @entity268 concentrations were measured by RIA. Interestingly, SDR pituitary cells were hyperresponsive to 1 and 10 nM @entity11523 , which induced a rise in intracellular @entity268 concentrations 50% greater than that observed in control cultures (n = 3 separate experiments; P < 0.05 and P < 0.01, respectively). Replacement of @entity11249 , by osmotic minipump (10 microg/h for 72 h), resulted in the suppression of @entity11523 mRNA levels (P < 0.01), whereas SS and NPY mRNA levels were increased (P < 0.05), compared with vehicle-treated controls (n = 5 animals/treatment group). Consonant with the fall in hypothalamic @entity11523 mRNA was a decrease in pituitary @entity56965 mRNA levels. Although replacement of @entity2135 ( @entity2135 ), by osmotic pump (5 microg/h for 72 h), resulted in a rise in circulating @entity2135 concentrations comparable with that observed after @entity11249 replacement, @entity2135 treatment was ineffective in modulating @entity11523 , SS, or NPY mRNA levels. However, @entity2135 treatment did reduce pituitary @entity56965 mRNA levels, compared with vehicle-treated controls (P < 0.05). These results further validate the role of @entity11249 as a negative regulator of hypothalamic @entity11523 expression, and they suggest that SS and NPY act as intermediaries in @entity11249 -induced suppression of hypothalamic @entity11523 synthesis. These data also demonstrate that increases in circulating @entity2135 are not responsible for changes in hypothalamic function observed after @entity11249 treatment. Finally, this report establishes modulation of @entity56965 synthesis as a component of @entity11249 autofeedback regulation.

Hypothalamic/pituitary-axis of the spontaneous dwarf XXXX : autofeedback regulation of @entity11249 ( @entity11249 ) includes suppression of @entity11249 releasing-hormone receptor messenger ribonucleic acid.

@entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity56965 :: ('25321(Tax:10116)', 'Gene') :: ['GHRH receptor', 'GHRH-R'] @entity10969 :: ('24604(Tax:10116)', 'Gene') :: ['neuropeptide Y'] @entity11249 :: ('81668(Tax:10116)', 'Gene') :: ['GH'] @entity11523 :: ('29446(Tax:10116)', 'Gene') :: ['GHRH'] @entity2135 :: ('24482(Tax:10116)', 'Gene') :: ['IGF-I', 'insulin-like growth factor-I'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity1943 :: ('MESH:D013004', 'Chemical') :: ['somatostatin']
@entity35 :: (10116,Species) :: ['rat']
