Is Estrogen-Induced Pituitary Hyperplasia and Hyperprolactinaemia Mediated by Angiotensin II?

Abstract

Human and rat anterior pituitary glands (APG) contain local renin-angiotensin systems (RAS). In the rat APG renin, renin mRNA, angiotensin converting enzyme (ACE) and angiotensin II (A II) have been identified within gonadotrophs (Naruse et al. 1986; Deschepper et al. 1986; Thomas and Sernia 1990). Angiotensinogen (AGEN) and AGEN mRNA have also been found in the rat APG but their localization remains still unclear (Ganong and Deschepper 1989; Healy 1992). Main target sites for A II action in APG seem to be lactotrophs. Specific A II binding sites have been identified mainly on lactotrophs and A II has been shown to stimulate prolactin (PRL) secretion (Aguilera et al. 1982; Denef and Schramme 1985). Recently, we have found that A II stimulated the proliferation of lactotrophs isolated from the estrogen-induced pituitary tumors in the rat (Kunert-Radek and Pawlikowski 1992). Moreover, an ACE inhibitor, enalapril, was found to prevent the pituitary proliferative response to a single injection of estradiol in rats (Mucha et al. 1993). Estrogens are well known to stimulate the pituitary cell proliferation and tumorigenesis and the estrogen-induced APG hyperplasia involves mainly lactotrophs (Zondek 1936; Miętkiewski 1959; Lloyd et al. 1975). Estrogens have been also found to enhance the prolactin secretion (Nicoll and Meites 1962). On the other hand, estrogens were found to increase the AGEN plasma levels (Menard et al. 1970) and to enhance AGEN mRNA expression in the liver, brain (Kunapuli et al. 1987) and pituitary (Healy et al. 1992). Thus, a question arises whether A II is involved in the estrogen action on APG. The aim of the experiments presented below was to test the hypothesis in question.