Utilization of electron microscopic techniques in the in vitro study of adenohypophysial function and regulation

Morphologic studies of human adenohypophysial cells using immunocytochemistry and electron microscopy have characterized the hormone-producing cell types of the normal gland and pituitary adenomas. The classifications which have emerged allow more accurate clinicopathologic correlations than ever before, but have also raised new questions concerning cytogenesis, pathogenesis, and structure-function correlations. We report the results of studies which marry the conventional morphologic techniques of light microscopy, immunohistochemistry, electron microscopy, and ultrastructural immunocytology with functional analyses using tissue culture and radioimmunoassay of hormones released into culture media. The hormone secretory activity of nontumorous and adenomatous pituitary cells is correlated with their structural features; their secretory responses to several adenohypophysiotropic factors are compared with morphologic alterations which are characterized at the light and electron microscopic levels by morphometric analysis. These studies have shown that hypothalamic stimulating hormones increase hormone release by their target cells and alter the ultrastructural appearance of the affected cells by increasing organelles involved in hormone synthesis. Inhibitory drugs and adrenal and gonadal steroids are capable of suppressing hormone release by some tumors and also give rise to morphologic changes which correlate with the functional inhibition. Hormone release by clinically nonfunctioning adenomas has been characterized and the behavior of these tumor cells in vitro sheds some light on the reasons for lack of clinical symptomatology. The plurihormonal nature of several nontumorous and adenomatous pituitary cell types has been characterized in vitro. The results of these studies provide the basis for more accurate structure-function correlations which can be used to study the hormonal milieu in vivo, to predict the role of pathogenetic factors in pituitary tumorigenesis, and to assess the therapeutic value of stimulating or inhibiting hormones and drugs.