Conclusions

It now seems beyond doubt that the brain does represent a physiological target for GH action. GHRs are expressed in a region- and cell-specific fashion, are developmentally

Fig. 9. GH feedback regulation of GHRH in Dw and Tgr rats. Comparison of the effects of chronic GH exposure from GC cell implants on the number of hypothalamic cells expressing GHRH mRNA in dwarf (Dw), normal Wistar-Furth (WF/-), and transgenic growth-retarded (WF/Tgr) rats. The high GHRH in dwarf rats was markedly suppressed by GC implants; a suppression was also evident in normal, but not Tgr rats. ### p < 0.001 compared to Dw, ***p < 0.001 compared to WF/-. From ref. 134.

Fig. 9. GH feedback regulation of GHRH in Dw and Tgr rats. Comparison of the effects of chronic GH exposure from GC cell implants on the number of hypothalamic cells expressing GHRH mRNA in dwarf (Dw), normal Wistar-Furth (WF/-), and transgenic growth-retarded (WF/Tgr) rats. The high GHRH in dwarf rats was markedly suppressed by GC implants; a suppression was also evident in normal, but not Tgr rats. ### p < 0.001 compared to Dw, ***p < 0.001 compared to WF/-. From ref. 134.

regulated, and are subject to peripheral regulation by GH and other endocrine factors. Hypothalamic GHRs are involved in mediating autofeedback regulation of GH secretion via powerful effects on GHRH and SRIF activity and probably on the GHRP system as well. These actions may be direct or indirect via other hypothalamic systems, such as those expressing NPY. Much less is known about the role of GH in other brain sites, about how GH gains access to these sites, and whether this access is by diffusion or by some form of regulated transport. Brain GHRs are subject to a different developmental and endocrine regulation from those in peripheral tissues. Both GH and GHR are present in fetal life, although what physiological roles they play remains unclear. Beneficial effects of GH therapy on mood in GH-deficient adults imply that GH may affect CNS function in adult life, but further experimental studies are needed to evaluate the importance of these and whether they could be exploited for therapeutic benefit.

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