Secretion of Renin–Angiotensin System (RAS) Components by Normal and Tumoral Lactotropes: A Comparative Study Using Reverse Hemolytic Plaque Assay (RHPA) and Immunoelectron Microscopy

Abstract

S U M M A R YImmunodetection of renin-angiotensin system (RAS) components indicates that there is a local RAS in anterior pituitary cells, particularly in lactotropes. We have attempted to determine if RAS molecules are secreted by lactotropes and the secretory pathways and intracellular sites of maturation. We investigated the secretory activity of individual lactotropes, using the reverse hemolytic plaque assay (RHPA), with GH3B6 tumor cells and normal male rat pituitary cells. We also determined the subcellular distributions of RAS components in these cells. Both tumor and normal cells secreted angiotensinogen, prorenin, renin, angiotensin I, angiotensin-converting enzyme, and angiotensin II, although at different levels. The percentage of secretory cells was generally higher in tumor lactotropes than in normal cells. The subcellular distribution of RAS components obtained by immunoperoxidase was very similar in both cell types, although the intensities of immunoreactivity differed. Cleaved and uncleaved components were found in rough endoplasmic reticulum (RER), Golgi saccules, and secretory granules, all compartments of the secretory pathway. The cleaved components in the RER suggest the existence of early maturation, whereas the presence of uncleaved products in the secretory granules of normal lactotropes might indicate late maturation sites.

Regulation of cell volume and water transport – An old fundamental role of the renin angiotensin aldosterone system components at the cellular level

“…The appearance of a sophisticated kidney function in mammals made it possible the efficient regulation of blood volume and blood pressure through the activation of the systemic renin angiotensin aldosterone system (RAAS). Independently of a circulatory RAAS, the expression of RAAS components at cellular level in vertebrates because immunodetection of renin-angiotensin system (RAS) components were found in anterior pituitary cells, particularly in lactotropes [36] and prorenin, renin and angiotensinogen were identified not only in lactotropes and gonadotropes but also in somatotropes, corticotropes, and thyrotropes. The highest levels of renin were detected in lactotropes and gonadotropes [37].…”

The Involvement of Angiotensin Type 1 and Type 2 Receptors in Estrogen-Induced Cell Proliferation and Vascular Endothelial Growth Factor Expression in the Rat Anterior Pituitary

“…Immunohistochemical studies have demonstrated that anterior pituitary cells are also able to express the components of RAS [34, 35]. At the other hand, angiotensin peptides have been shown to affect the growth of anterior pituitary cells.…”