Pituitary morphology in anencephalic human fetuses.

Anencephalic fetuses provide a model of pituitary development in the absence of the hypothalamus. We studied pituitaries of 10 anencephalic fetuses at various stages of gestation using formalin-fixed paraffin-embedded tissue with immunocytochemistry for known adenohypophysial hormones, the transcription factors Pit-1 and SF-1, cytokeratins and S-100 protein. Ten age- and sex-matched fetuses with no endocrine abnormality were controls. At 17-18 weeks of gestation, pituitaries of 4 anencephalics had no posterior lobe; the number and size of cells containing adenohypophysial hormones and the transcription factors were indistinguishable from controls, however, juxtanuclear cytokeratin-positive fibrous bodies were inconspicuous in anencephalics and were prominent in the adenohypophyses of controls. At 26-28 weeks of gestation, there was a marked reduction in number and staining intensity of cells containing SF-1, alpha-subunit of glycoprotein hormones and both gonadotropin beta-subunits in the adenohypophyses of 2 anencephalics. After 32 weeks, corticotropes were reduced in number and size, and gonadotropes were almost entirely absent; in contrast, somatotropes, lactotropes and thyrotropes were numerous. S-100 protein immunoreactivity was increased in anencephalic pituitaries after 32 weeks, when it was found in numerous cells that did not have the usual morphology of folliculo-stellate cells. These data indicate that adenohypophysial cells can differentiate in the absence of the hypothalamus, and that the transcription factors implicated in cytodifferentiation are expressed in anencephalic pituitaries, but that hypothalamic factors are essential for maintenance of gonadotropes and corticotropes. The functional role of fibrous bodies in somatotropes is unknown, but these structures are inconspicuous in the adenohypophyses of anencephalics. Finally, the appearance of S-100 protein-immunoreactive cells is abnormal in anencephalic fetuses.