Noradrenergic Regulation of Hypothalamic Cells that Produce Growth Hormone‐Releasing Hormone and Somatostatin and the Effect of Altered Adiposity in Sheep

Abstract

The growth hormone (GH) axis is sensitive to alteration in body weight and there is evidence that central noradrenergic systems regulate neurones that produce growth hormone-releasing hormone (GHRH) and somatostatin (SRIF). This study reports semiquantitative estimates of the noradrenergic input to neuroendocrine GHRH and SRIF neurones in the sheep of different body weights. We also studied the effects of altered body weight on expression of dopamine beta-hydroxylase (DBH), the enzyme that produces noradrenalin from dopamine. Ovariectomised ewes were made Lean (39.6 +/- 2.6 kg; Mean +/- SEM) by dietary restriction, whereas Normally Fed animals (61.2 +/- 0.8 kg) were maintained on a regular diet. Brains were perfused for immunohistochemistry and in situ hybridisation. The Mean +/- SEM number of GHRH-immunoreactive (-IR) cells was lower in Normally Fed (65 +/- 7) than in Lean (115 +/- 14) animals, whereas the number of SRIF-IR cells was similar in the two groups (Normally Fed, 196 +/- 17; Lean 230 +/- 21). Confocal microscopic analysis revealed that the percentage of GHRH-IR cells (Normally Fed 36 +/- 1.5% versus Lean 32 +/- 4.6%) and percentage of SRIF-IR cells (Normally Fed 30 +/- 40.4% versus Lean 32 +/- 2.3%) contacted by noradrenergic fibres did not change with body weight. FluoroGold retrograde tracer injections confirmed that noradrenergic projections to the arcuate nucleus are from ventrolateral medulla and noradrenergic projections to periventricular nucleus arise from the ventrolateral medulla, nucleus of solitary tract, locus coeruleus (LC) and the parabrachial nucleus (PBN). DBH expressing cells were identified using immunohistochemistry and in situ hybridisation and the level of expression (silver grains/cell) quantified by image analysis. The number of DBH cells was similar in Normally Fed and Lean animals, but the level of expression/cell was lower (P < 0.02) in the PBN and LC of Lean animals. These results provide an anatomical basis for the noradrenergic regulation of GHRH and SRIF cells and GH secretion. Altered activity or noradrenergic neurones in the PBN and LC that occur with reduced body weight may be relevant to the control of GH axis.