Pituitary adenomas: tumor cell growth by cluster formation. Pattern analysis based on immunohistochemistry

Abstract

The topographical distribution of adrenocorticotropic hormone, growth hormone and prolactin was studied in nine multihormonal pituitary adenomas and two normal adenohypophyses using quantitative immunohistochemical methods. For each pituitary hormone paraffin sections stained by antihormone antibodies were scanned with a light microscope equipped with a projection and scanning device. The number of immunoreactive cells of each square in the grid was counted and transformed into pseudocolors. In this way, the distribution of each hormone was documented. A chi-square test was applied to these distribution patterns to prove randomness. A nonrandom distribution of immunoreactive cells was observed in all pituitary adenomas and normal pituitary glands. Cluster formations of immunoreactive cells were found for each hormone. The clusters were surrounded by halo-like areas of decreasing number of immunoreactive cells from center to periphery. The cluster-halo type of immunoreactive cells was found not only in the adenomas but also in the normal pituitary gland. This may be explained by the similarity of biological processes during cell proliferation either in normal development or in adenoma formation. It can be concluded from our studies that pituitary adenomas in most cases develop by multicentric but not diffuse proliferation of cell clones of different endocrine activity.

Mechanisms by which the orexigen NPY regulates anorexigenic α-MSH and TRH

“…To generate ␣-MSH, its prohormone POMC must undergo a series of proteolytic cleavages catalyzed by the enzymes prohormone convertase-1 [PC1, also referred to as PC3 (63)] and prohormone convertase-2 (PC2), followed by further modification via carboxypeptidase E (CPE) and N-acetyltransferase (11,44,67). Because of this maturation process, it is critical to know whether NPY regulates ␣-MSH peptide content rather than to focus only on changes at the level of POMC transcription.One way that ␣-MSH exerts its anorexigenic actions is by binding melanocortin receptors on TRH neurons in the PVN, causing the phosphorylation of cAMP response element-binding protein (CREB), thereby increasing prepro-TRH expression (15,21,46,59). TRH is essential for energy balance because it regulates the hypothalamic-pituitary-thyroid (HPT) axis that controls whole body metabolism (22,33).…”

“…One way that ␣-MSH exerts its anorexigenic actions is by binding melanocortin receptors on TRH neurons in the PVN, causing the phosphorylation of cAMP response element-binding protein (CREB), thereby increasing prepro-TRH expression (15,21,46,59). TRH is essential for energy balance because it regulates the hypothalamic-pituitary-thyroid (HPT) axis that controls whole body metabolism (22,33).…”