Ultrastructure, immunohistochemistry and hormone release of pituitary adenomas in relation to prolactin production

Abstract

Fifteen cases of pituitary adenoma, 14 of which were associated with hyperprolactinemia, were studied by observation and granule morphometry of electron micrographs, immunohistochemistry and sequential observation of in vitro release with regard to hormone production, storage and secretion. Adenoma cells of 6 cases with marked elevation of plasma prolactin were sparsely granulated, showed characteristic ultrastructures including the presence of small secretory granules, well developed Golgi and rough membranes, misplaced exocytosis, and positive or negative immunostaining for prolactin. These adenomas also showed vigorous release of the hormone into the circulation and/or culture medium. In vitro studies showed that negative immunostaining of adenoma cells did not preclude the production and secretion of the hormone. One densely granulated adenoma containing cells with numerous lactotroph type granules showed moderate release of prolactin into the circulation. In an acromegalic case associated with both high plasma growth hormone and prolactin, some cells were shown by immunohistochemistry to store both hormones There were 4 adenomas which could not be shown to produce, store and secrete prolactin by any method available.

The Relationship Between Serum Prolactin and Immunocytochemical Staining for Prolactin in Patients With Pituitary Macroadenomas

“…Nevertheless absence of immunostaining for prolactin in a tissue specimen does not necessarily mean the tumour has not secreted prolactin, as we and others (Kovacs et al, 1977) have shown that immunostaining may be variable within the tumour, some sections showing no prolactin and others showing positive immunostaining. It is also possible that occasional chromophobe prolactinomas do not immunostain for prolactin because prolactin is being actively secreted but not stored (Kovacs et al, 1977;Kameya et al, 1980). Despite the above reservations, our findings showed a significant difference between the pretreatment serum prolactin levels of patients with tumours showing none, and in those with many cells staining for prolactin.…”

Do the limits of serum prolactin in disconnection hyperprolactinaemia need re‐definition? A study of 226 patients with histologically verified non‐functioning pituitary macroadenoma

“…This could be mainly attributed to preoperative treatment with a dopamine agonist, which is capable of reducing the tumour immunostaining for PRL, and may therefore, not allow the correct immunohistochemical characterization 5,20 . Moreover, the diagnosis of a prolactinoma may be missed in cases of inhomogeneous PRL immunostaining within a single tumour 5 or when the PRL is actively secreted but not stored, thereby leading to negative staining 21 …”

Heterogeneity of pituitary adenoma cell subpopulations from acromegalic patients obtained by Percoll density gradient centrifugation

“…This has been demonstrated by several in vitro studies (1)(2)(3)(4)(5)(6) and by morphological techniques (1,(7)(8)(9)(10)(11)(12)(13). However, pituitary adenomas from acro¬ megalic patients are very heterogeneous with re¬ spect to their cellular composition.…”