title: Angiotensin II (AII) and adrenocorticotropin release: modulation by estradiol of the AII biological activity and binding characteristics in anterior pituitary dispersed cells.
abstract: The present studies were designed to test if estrogens influence basal and angiotensin II (AII)-stimulated ACTH release and the binding characteristics of AII receptors in isolated anterior pituitary (AP) cells from estrogen-deplete and estrogen-replete rats incubated in vitro. AP cells were obtained from various adult donors: randomly cycling (rc), 10-day ovariectomized (Ovx), Ovx with estradiol restored at a circulating physiological level (Ovx + lEB), Ovx with estradiol at a supraphysiological circulating level (Ovx + hEB); and male (m) rats. The amount of ACTH released under basal conditions was similar in the rc, Ovx + lEB, and m groups, although this amount was significantly greater (P less than 0.02) than that in the Ovx and Ovx + hEB groups. The ACTH-releasing activity (CRA) of AII was concentration dependent (10(-9)-10(-6) M) in all cells. The rank order of the CRA of AII in the groups varied as follows: rc = Ovx + lEB greater than Ovx = Ovx + hEB = m. The slopes of the AII responses were similar. Estradiol addition in vitro did not modify either basal or AII-stimulated ACTH release in any group of cells. AII binding studies indicated that AP cells from donors with different circulating estradiol levels had similar apparent equilibrium dissociation constants (Kd, 16-30 nM). However, the maximum binding capacities in AP cells from the m, Ovx, and Ovx + hEB groups (40, 51, and 49 fmol/10(6) cells, respectively) were significantly lower (P less than 0.05) than those in the rc and Ovx + lEB groups (77 and 81 fmol/10(6) cells, respectively). In summary, these studies indicate that 1) circulating levels of estradiol are able to modulate spontaneous ACTH release by dispersed AP cells; and 2) circulating estradiol, at a lower or higher level than that during the estrous cycle, decreases the in vitro ACTH-releasing activity of AII, possibly through a reduction in the number of AP AII receptors. These results further suggest that estrogen is likely to have a physiological role in corticotropic function.
authors.affiliation: Centro de Referencia de Radioinmunoensayo, La Plata, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Spinedi
authors.forename: L
authors.initials: L
authors.lastname: Herrera
authors.forename: A
authors.initials: A
authors.lastname: Chisari
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D004971:Estrus; D005260:Female; D007700:Kinetics; D008297:Male; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
chemical_list: D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004958:Estradiol; D000324:Adrenocorticotropic Hormone