Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats

Growth hormone (GH) therapy substantially improves several cognitive functions in hypopituitary experimental animals and in humans. Although a number of biochemical correlates to these effects have been characterized, there are no comprehensive analysis available examining effects of GH on the brain. Hypophysectomized female rats were given replacement therapy with cortisol and thyroxine (= hx). Subcutaneous infusions of bovine GH (bGH, henceforth designated GH) were supplied in osmotic minipumps for 6 days (= hx + GH). To evaluate whether GH normalized specific transcript expression levels in cerebral cortex, pituitary-intact rats were used as normal controls. DNA microarrays (Affymetrix) of cerebrocortical samples showed that 24 transcripts were changed by more than 1.5-fold by GH treatment in addition to being normalized by GH treatment. The expression of three selected highly regulated transcripts was confirmed by quantitative real-time polymerase chain reaction analysis. These were the GABAB receptor 1, Lissencephaly-1 protein (LIS-1), and hemoglobin b or beta-globin. A similar regulation was found for hemoglobin b also in the hippocampus. Both the GABAB receptor 1 and hemoglobin b may have importance for the previously described neuroprotective and perhaps cognitive potential of GH treatment.Altogether, these results show that short term GH treatment affects a number of transcripts in cerebral cortex with various biological functions. These transcripts represent potential novel mechanisms by which GH can interact with the brain.