| dc.description | Growth hormone (GH) exerts important biological
effects primarily related to growth and metabolism.
However, the role of GH signaling in the brain is still
elusive. To better understand GH functions in the brain, we
mapped the distribution of GH-responsive cells and identified
the receptors involved in GH central effects. For this
purpose, mice received an acute intraperitoneal challenge
with specific ligands of the GH receptor (mouse GH),
prolactin receptor (prolactin) or both receptors (human
GH), and their brains were subsequently processed
immunohistochemically to detect the phosphorylated form
of STAT5 (pSTAT5). GH induced pSTAT5 immunoreactivity
in neurons, but not in astroglial cells of numerous
brain regions, including the cerebral cortex, nucleus
accumbens, hippocampus, septum and amygdala. The most
prominent populations of GH-responsive neurons were
located in hypothalamic areas, including several preoptic
divisions, and the supraoptic, paraventricular, suprachiasmatic,
periventricular, arcuate, ventromedial, dorsomedial,
tuberal, posterior and ventral premammillary nuclei.
Interestingly, many brainstem structures also exhibited
GH-responsive cells. Experiments combining immunohistochemistry
for pSTAT5 and in situ hybridization for GH
and prolactin receptors revealed that human GH induced
pSTAT5 in most, but not all, brain regions through both
prolactin and GH receptors. Additionally, males and females exhibited a similar number of GH-responsive cells
in forebrain structures known to be sexually dimorphic. In
summary, we found GH-responsive cells primarily distributed
in brain regions implicated in neurovegetative,
emotional/motivational and cognitive functions. Our findings
deepen the understanding of GH signaling in the brain
and suggest that central GH signaling is likely more ample
and complex than formerly recognized | |
