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

Hanna Lawnicka,Dorota Ptasinska-Wnuk,Marek Pawlikowski,Jolanta Kunert-Radek,Slawomir Mucha,Henryk Stepien

doi:10.1100/2012/358102

Hanna Lawnicka, Dorota Ptasinska-Wnuk + Show 4 more

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https://doi.org/10.1100/2012/358102

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Journal: TheScientificWorldJournal	Publication Date: Jan 1, 2012
Citations: 4	License type: CC BY 3.0

Affiliation: Medical University of Lodz

Abstract

The aim of our study was to examine the involvement of renin-angiotensin system (RAS) in estrogen-induced lactotropes proliferation and vascular endothelial growth factor (VEGF) expression in rat pituitary. The study was performed on Fisher 344 rats underwent 8-day treatment with diethylstilboestrol (DES). The proliferation index (PCNA) and VEGF expression in pituitary sections were estimated using immunohistochemical methods. Treatment with DES increased the number of PCNA-positive cells, VEGF-positive cells, and VEGF-positive blood vessels in pituitary. Stimulatory effect of estrogen on cell proliferation and VEGF expression in blood vessels was attenuated by losartan, PD123319, and captopril. VEGF immunoreactivity in pituitary cells of DES-treated rats was decreased by AT1 antagonist and not changed by AT2 blocker and ACE inhibitor. Our findings suggest the involvement of RAS in DES-induced cell proliferation and VEGF expression in pituitary. Both the AT1 and AT2 receptors appear to mediate the estrogen-dependent mitogenic and proangiogenic effects in rat pituitary.

Highlights

Estrogens are well known to stimulate, both directly and indirectly, the cellular proliferation in anterior pituitary, and their growth-promoting effects are largely confined to the lactotropes [1,2,3]
Heaney et al have revealed the cyclic expression of the pituitary tumor transforming gene, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF) during the rat estrus cycle, with maximal expression occurring with peak serum estradiol (E2), increased pituitary proliferation and angiogenesis [5]
The 8-day treatment with DES resulted in a significant elevation in the proliferation index, expressed as a number of the proliferating cell nuclear antigen (PCNA)-immunopositive cells per 1000 randomly scattered cells, in anterior pituitary of rats (Figures 1 and 2(b))

Summary

Introduction

Estrogens are well known to stimulate, both directly and indirectly, the cellular proliferation in anterior pituitary, and their growth-promoting effects are largely confined to the lactotropes [1,2,3]. Heaney et al have revealed the cyclic expression of the pituitary tumor transforming gene (pttg), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) during the rat estrus cycle, with maximal expression occurring with peak serum estradiol (E2), increased pituitary proliferation and angiogenesis [5]. The functional role of estrogen receptor (ERα) in cell proliferation, prolactin (PRL). E2 has been found to induce the transforming growth factor-beta 3 (TGF-β3) secretion from lactotropes. TGF-β3 stimulated, in turn, the folliculostellate (FS) cells to release both VEGF and bFGF, the potent mitogen for prolactin- (PRL-) secreting cells [7]. Tumor formation in estrogeninduced prolactinoma was shown to be associated with the development of the direct arterial blood supply leading the anterior pituitary cells to escape from hypothalamic

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