Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats.

Female F344 rats treated chronically with diethylstilbestrol (DES) develop prolactin (PRL)-producing pituitary tumors. These tumors are larger in female than in male rats. To investigate gender differences in DES-induced pituitary tumor formation, we employed female and male rats and neonatally androgenized females, which received 100 microg of testosterone propionate (TP) after 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 treatment, control pituitary weight and serum PRL were similar in gonadectomized males (GDX), ovariectomized females (OVX) and androgenized-ovariectomized 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 (NE(2)R) amounted to >100 fmol/mg DNA in all rats receiving DES. However, NE(2)R 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 similar profile was found for cytosolic progestin receptors. Using electron microscopy (EM), hyperplasia/hypertrophy of lactotropes was found in all DES-stimulated pituitaries. However, tumors of OVX + DES rats were enriched in hyperstimulated typical lactotropes, i.e., cells with high rate of hormonal synthesis, processing and secretion. Instead, tumors from GDX + DES and OVX + TP + DES rats were a mixture of typical and atypical lactotropes, i.e. a cell subpopulation with refractory secretory response and a few gonadotropes. In agreement with these data, immunoreactive pituitary PRL was lower in OVX + DES than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity to DES, serum and tumor PRL, NE(2)R and progestin receptors between estrogenized female rats on one side and male and TP-androgenized females 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 hypothalamic centers, may condition the response to DES stimulation later in life.

Telarquia prematura: aumento de la actividad estrogénica total en el plasma / Premature thelarche: increased of total estrogenic activity in the serum

Con el propósito de estudiar las causas de la telarquia prematura, se comparó el perfil hormonal y las características de los genitales internos mediante ultrasonografía pelvians en 41 niñas afectadas, de 21,15 ñ 9,74 meses de edad y e 31 controles de la misma edad y nivel socioeconómico y se buscó contaminación de los alimentos con zearalenona y dietilbestrol por cromatografía en capa delgada. La actividad estrogénica total en el plasma de las niñas, así como plasma y tejidos de pollo, se midió por el método de radiorreceptor. Las concentraciones basales de LH, FSH, prolactina y estradiol eran similares en pacientes y controles. La actividad estrogénica total fue significativamente mayor en las niñas con telarquia (201 ñ 102 vs 78 ñ 20 pg E2 equivalente) y descendió a niveles similares que en los controles (75 ñ 8 pg E2) al desaparecer la telarquia. La respuesta a LHRH en pacientes con telarquia fue mayor para FSH (28,7 ñ 17,5 Uµ/ml) que para LH (5,01 ñ 2,7 Uµ/ml). El tamaño del útero y la maduración ósea fueron similares en ambos grupos, pero el volumen ovárico medio fue mayor en pacientes con telarquia. No se detectaron contaminantes exógenos en la sangre de las niñasy los tejidos de 25 pollos. La actividad estrogénica en el plasma de las aves cumplía las recomendaciones internacionales (FAO). La respuesta de FSH al factor liberador, el mayor volumen ovárico y el aumento de la actividad estrogénica sugieren activación parcial del eje hipotálamo-hipofisiario-gonadal de predominio FSH en las niñas con telarquia prematura