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 andr...
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todo:paper_00283835_v72_n2_p80_Piroli2023-10-03T14:38:55Z Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats Piroli, G.G. Torres, A. Pietranera, L. Grillo, C.A. Ferrini, M.G. Lux-Lantos, V. Aoki, A. De Nicola, A.F. Fischer rats Gonadal steroid receptors Gonadal steroids Immunocytochemistry Lactotropes Pituitary tumors Prolactin Sexual dimorphism androgen diethylstilbestrol DNA estrogen receptor progesterone receptor prolactin steroid receptor testosterone propionate animal experiment animal tissue article carcinogenesis cell hyperplasia cell population controlled study female hormonal regulation hypertrophy hypophysis tumor male nonhuman priority journal prolactin blood level rat sex difference tumor growth 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 μg 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 (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 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, NE2R 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. Copyright (C) 2000 S. Karger AG, Basel. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00283835_v72_n2_p80_Piroli |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Fischer rats Gonadal steroid receptors Gonadal steroids Immunocytochemistry Lactotropes Pituitary tumors Prolactin Sexual dimorphism androgen diethylstilbestrol DNA estrogen receptor progesterone receptor prolactin steroid receptor testosterone propionate animal experiment animal tissue article carcinogenesis cell hyperplasia cell population controlled study female hormonal regulation hypertrophy hypophysis tumor male nonhuman priority journal prolactin blood level rat sex difference tumor growth |
| spellingShingle |
Fischer rats Gonadal steroid receptors Gonadal steroids Immunocytochemistry Lactotropes Pituitary tumors Prolactin Sexual dimorphism androgen diethylstilbestrol DNA estrogen receptor progesterone receptor prolactin steroid receptor testosterone propionate animal experiment animal tissue article carcinogenesis cell hyperplasia cell population controlled study female hormonal regulation hypertrophy hypophysis tumor male nonhuman priority journal prolactin blood level rat sex difference tumor growth Piroli, G.G. Torres, A. Pietranera, L. Grillo, C.A. Ferrini, M.G. Lux-Lantos, V. Aoki, A. De Nicola, A.F. Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats |
| topic_facet |
Fischer rats Gonadal steroid receptors Gonadal steroids Immunocytochemistry Lactotropes Pituitary tumors Prolactin Sexual dimorphism androgen diethylstilbestrol DNA estrogen receptor progesterone receptor prolactin steroid receptor testosterone propionate animal experiment animal tissue article carcinogenesis cell hyperplasia cell population controlled study female hormonal regulation hypertrophy hypophysis tumor male nonhuman priority journal prolactin blood level rat sex difference tumor growth |
| description |
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 μg 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 (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 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, NE2R 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. Copyright (C) 2000 S. Karger AG, Basel. |
| format |
JOUR |
| author |
Piroli, G.G. Torres, A. Pietranera, L. Grillo, C.A. Ferrini, M.G. Lux-Lantos, V. Aoki, A. De Nicola, A.F. |
| author_facet |
Piroli, G.G. Torres, A. Pietranera, L. Grillo, C.A. Ferrini, M.G. Lux-Lantos, V. Aoki, A. De Nicola, A.F. |
| author_sort |
Piroli, G.G. |
| title |
Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats |
| title_short |
Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats |
| title_full |
Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats |
| title_fullStr |
Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats |
| title_full_unstemmed |
Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats |
| title_sort |
sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in f344 rats |
| url |
http://hdl.handle.net/20.500.12110/paper_00283835_v72_n2_p80_Piroli |
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| _version_ |
1807321152358449152 |