Changes in growth hormone (GH), GH receptor, and GH signal transduction in hippocampus of congenital hypothyroid rats

Recent studies have shown that, like thyroid hormone (TH), growth hormone (GH) plays a critical role in development of the brain. However, it is still unclear whether the functions of the two hormones are locally orchestrated in the brain or whether TH has a permissive effect on GH in the central nervous system as it does in the periphery. To address this question, the present study investigated the changes in local expression of GH and GH receptor (GHR) and the activity of GH signaling molecules in the hippocampus of congenitally hypothyroid (CHT) rats. As demonstrated by morphometric measurements and the Y-maze test, CHT rats had decreased neurons and weaker Nissl staining in the stratum pyramidal/granule in the hippocampus and a reduced acquisition of safe place recognition memory. Analyses of QPCR and Western blot revealed a substantially decreased hippocampal expression of GH and GHR, accompanied by a corresponding decrease in phosphorylation of JAK2 and STAT5 in the CHT rats. These changes were, at least in part, corrected by systemic supplement of T3. The findings provide the first direct evidence suggesting that the functional autocrine and paracrine regulation of GH in the CNS is orchestrated by TH.