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Oophorectomy improves pituitary activin inhibitory function preventing lactotroph hyperplasia development.
Peña-Zanoni, Milagros; Faraoni, Erika Yanil; Abeledo-Machado, Alejandra; Perez, Pablo Anibal; Marcial López, Carla Agustina; Camilletti, María Andrea; Gutierrez, Silvina; Rulli, Susana B; Diaz-Torga, Graciela.
Afiliación
  • Peña-Zanoni M; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
  • Faraoni EY; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
  • Abeledo-Machado A; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
  • Perez PA; Centro de Microscopia Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
  • Marcial López CA; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
  • Camilletti MA; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
  • Gutierrez S; Centro de Microscopia Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
  • Rulli SB; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
  • Diaz-Torga G; Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina.
Endocr Relat Cancer ; 29(6): 359-373, 2022 05 11.
Article en En | MEDLINE | ID: mdl-35324456
ABSTRACT
Among pituitary adenomas, prolactinomas are the most frequently diagnosed (about 50%). Dopamine agonists are generally effective in the treatment of prolactinomas. However, a subset of about 25% of patients does not respond to these agents. The management of drug-resistant prolactinomas remains a challenge for endocrinologists and new inhibitory treatments are needed. Pituitary activins inhibit lactotroph function. Its expression and action were found reduced in animal models of lactotroph hyperplasia (female mice overexpressing the B subunit of the human chorionic gonadotrophin and female mice knockout for dopamine receptor type 2). In these models, an oophorectomy avoids prolactinoma development. Hormonal replacement with oestradiol and/or progesterone is not enough to reach the tumor size observed in transgenic females. We postulated that the loss of gonadal inhibins after an oophorectomy contributes to prevent hyperplasia development. Here, we demonstrated that an oophorectomy at 2 months age recovers the following in adulthood (i) pituitary activin expression, (ii) activin receptor expression specifically in lactotroph population, (iii) activin biological activity in lactotrophs with a concomitant reduction of Pit-1 expression. To summarize, when an oophorectomy is performed, inhibins are lost and the inhibitory action of pituitary activins on lactotroph population is recovered, helping to prevent lactotroph hyperplasia development. These results emphasize the importance of the inhibitory action of activins on lactotroph function, positioning activins as a good therapeutic target for the treatment of resistant prolactinomas.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Hipofisarias / Prolactinoma / Lactotrofos Límite: Adult / Animals / Female / Humans Idioma: En Revista: Endocr Relat Cancer Asunto de la revista: ENDOCRINOLOGIA / NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Argentina

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Hipofisarias / Prolactinoma / Lactotrofos Límite: Adult / Animals / Female / Humans Idioma: En Revista: Endocr Relat Cancer Asunto de la revista: ENDOCRINOLOGIA / NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Argentina