INVESTIGADORES
DE NICOLA Alejandro Federico
artículos
Título:
Levonorgestrel antagonismo on estrogen-induced pituitary tumors is mediated by progesterona receptors
Autor/es:
REY-ROLDAN E.B.; GRILLO C.; PIETRANERA L.; LIBERTUN C.; DE NICOLA A.F.; PIROLI G.
Revista:
HORMONE AND METABOLIC RESEARCH
Editorial:
Thieme
Referencias:
Lugar: Alemania; Año: 2008 vol. 40 p. 245 - 250
ISSN:
0018-5043
Resumen:
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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.
