Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumorsin F344 rats

Female F344 rats treated chronically with diethylstilbestrol (DES) develop prolactin (PRL)-producing pituitary tumors. These tumors are larger in fema le than in male rats. To investigate gender differences in DES-induced pitu itary tumor formation, we employed female and male rats and neonatally andr ogenized females, which received 100 mu g of testosterone propionate (TP) a fter birth. At 3 months of age, all rats were deprived of their gonads and divided into control and DES-treated groups. Forty days after beginning tre atment, control pituitary weight and serum PRL were similar in gonadectomiz ed males (GDX), ovariectomized females (OVX) and androgenized-ovariectomize d females (OVX + TP), but weight of DES-induced tumors was 2.5-fold higher and serum PRL 5.6-fold higher in OVX + DES than in GDX + DES or OXV + TP DES (p < 0.001). At the pituitary level, nuclear estrogen receptors (NE2R) amounted to >100 fmol/mg DNA in all rats receiving DES. However, NE2R were lower in OVX + DES (101.3 +/- 9.0 fmol/mg DNA) than in GDX + DES (174.6 +/- 16.8; p < 0.05) and in OXV + DES + TP (150.3 +/- 27.7; p < 0.05). A simila r profile was found for cytosolic progestin receptors. Using electron micro scopy (EM), hyperplasia/hypertrophy of lactotropes was found in all DES-sti mulated pituitaries. However, tumors of OVX + DES rats were enriched in hyp erstimulated typical lactotropes, i.e., cells with high rate of hormonal sy nthesis, processing and secretion. Instead, tumors from GDX + DES and OVX TP + DES rats were a mixture of typical and atypical lactotropes, i.e. a c ell subpopulation with refractory secretory response and a few gonadotropes . In agreement with these data, immunoreactive pituitary PRL was lower in O VX + DES than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity to DES, serum and tumor PRL, NE2R and progestin receptors b etween estrogenized female rats on one side and male and TP-androgenized fe males on the other, may by due in part to heterogeneity of cell populations . Our data further suggest that neonatal hypothalamic exposure to androgens , as in normal males or androgenized females with masculinization of hypoth alamic centers, may condition the response to DES stimulation later in life . Copyright (C) 2000 S. Karger AG, Basel.