PITUITARY MORPHOLOGY OF TRANSGENIC MICE EXPRESSING BOVINE GROWTH-HORMONE

BACKGROUND: In mice transgenic for growth hormone (GH), the ectopic pr oduction of foreign GH causes gigantism and strong inhibition of endog enous pituitary GH. In human (h) GH transgenics, morphologic changes o ccurred not only in somatotrophs but in lactotrophs, corticotrophs, an d gonadotrophs as well. To distinguish between changes attributed to s omatotropic effect of hGH from those caused by its lactogenic effects, we studied the pituitary morphology of bovine (b) GH transgenics sinc e bGH has no lactogenic activity. EXPERIMENTAL DESIGN: Pituitaries fro m transgenic mice and nontransgenic siblings were studied by immunocyt ochemistry for adenohypophysial hormones, in situ hybridization for GH , prolactin (PRL), and proopiomelanocortin mRNAs, and electron microsc opy. RESULTS: Transgenic mice had an increased body weight and a signi ficantly decreased pituitary mass. In both sexes, GH immunoreactive ce lls were markedly reduced in size and moderately decreased in number, and the GH mRNA signal was lower compared with controls; ultrastructur ally, in somatotrophs, the cytoplasmic organelles involved in hormone synthesis were inconspicuous. Males were normoprolactinemic, and lacto trophs showed no morphologic changes. In transgenic females, PRL immun oreactive cells were hypertrophic and appeared to be more numerous. In transgenic males, a mild increase in size and number of follicle-stim ulating hormone/luteinizing hormone immunoreactive cells was noted. No changes were evident in corticotrophs and thyrotrophs in either sex. In the intermediate and posterior lobes, many corticotrophs and pituic ytes were GH immunoreactive, indicating expression of metallothionein- 1 (MT)-bGH transgene. CONCLUSIONS: Pituitaries of MT-bGH transgenic mi ce contained somatotrophs with morphologic features of inhibition. End ogenous GH production was not completely suppressed as indicated by th e presence of GH mRNA and GH immunoreactivity. Females had a mild incr ease in percentage of PRL immunoreactive cells, and previous biochemic al data proved that they were hyperprolactinemic. Substantial differen ces in pituitary morphology between transgenic MT-bGH mice and MT-hGH animals studied previously can be due to the fact that bGH is purely s omatotropic, whereas hGH is both somatotropic and lactogenic.