Increased Hypothalamic Somatostatin Expression in Mice Transgenic for Bovine or Human GH

Acute studies of GH removal by hypophysectomy or GH replacement in adult rats have shown that GH has a positive influence on its hypothalamic inhibitory hormone somatostatin (SRIH). The present study was undertaken to assess the effect of lifelong exposure to elevated GH on the development and differentiation of SRIH‐producing hypothalamic neurons, including comparison of differing GH levels and heterologous species of GH. Expression of somatostatin peptide and mRNA was evaluated using respective immunocytochemistry and in situ hybridization in brains of transgenic mice bearing constructs of either human (hGH) or bovine (bGH) linked to metallothionein (MT) promoter or bGH linked to phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates served as controls. All transgenic constructs resulted in high levels of circulating heterologous GH and significantly elevated body weights. Both bGH levels and body weights were higher in PEPCK‐bGH than in MT‐bGH mice; mean weights were not different between MT‐bGH and MT‐hGH mice. Numbers of SRIH‐immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of transgenic mice showed a two‐fold increase (P