IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Levonorgestrel antagonism on estrogen-induced pituitary tumors is madiated by progesterone receptors
Autor/es:
E. B. REY-ROLDÁN; C.A. GRILLO; L. PIETRANERA; C. LIBERTUN; A.F. DE NICOLA; G.G. PIROLI
Revista:
HORMONE AND METABOLIC RESEARCH
Editorial:
Georg Thierne Verlag KG
Referencias:
Lugar: New York; Año: 2007
ISSN:
0018-5043
Resumen:
Levonorgestrel Antagonism on Estrogen-induced Pituitary Tumors Is Mediated by Progesterone Receptors   E. B. Rey-Roldán1, C. A. Grillo2,3, L. Pietranera2,3, C. Libertun1,4, A. F. De Nicola2,3, G. G. Piroli2,3 1Laboratory of Neuroendocrinology, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires, Argentina2Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires, Argentina3Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina4Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina Abstract Using both in vitro and in vivo approaches, we studied the antagonism exerted by the synthetic progestin levonorgestrel on estrogen-induced prolactinomas, considering that levonorgestrel shows partial androgenic properties and that androgens inhibit estrogen-induced prolactin synthesis and secretion. In the tumors, binding of estrogens to their receptors was competed neither by progesterone receptor ligands nor by androgen receptor ligands, ruling out direct inhibitory effects of these drugs on tumor development. Progestin binding was competed by the progesterone receptor agonists progesterone and levonorgestrel, by the antagonist mifepristone, and also by the androgen dihydrotestosterone, whereas the androgen receptor antagonist hydroxyflutamide was a weak competitor. In addition, both progesterone receptor and androgen receptor ligands competed for binding to androgen receptors. In primary cultures of pituitary tumors, levonorgestrel decreased prolactin secretion, an effect that was blocked by mifepristone but not by hydroxyflutamide. In vivo results indicated that levonorgestrel inhibition of both estrogen-induced pituitary weight increment and hyperprolactinemia was reduced by mifepristone, whereas flutamide was unable to block levonorgestrel effects. Our results suggest that even when an interaction of levonorgestrel with androgen receptors in the tumors is possible, the antagonistic effects of levonorgestrel on tumor development and functionality are mediated by progesterone receptors.