the anti-estrogen 4-OH-tamoxifen showed a mild effect on lowering estrogenic effects from 19Nor derivatives. But neither an anti-progestin, nor an anti-aromatase had ANY effect. So the estrogenic effects are not the result of aromatisation, or progestagenic activity, and only caused for a very small part by the ER (confirming nandrolone's low affinity for the ER. Another study I found showed that nandrolone's affinity for the ER seems to increase with dose as well for those interested).
In the end, researchers simply concluded that they did not know what caused the estrogenic activity. Then I found this study (3). It shows that the prohormone estren , a metabolite of nandrolone (it converts to nandrolone via 3aHSD, alpha version of Nor-diol) can activate estrogenic transcripts via the AR. It seems plausible then, that nandrolone probably has similar activity, which perfectly explains its estrogenic nature.
It does present us with the problem that one cannot block the estrogenic effects of nandrolone unless they block the AR.
Seems like another blow for nandrolone to me. Will have to wait and see if said theory holds true in breast tissue as well as bone of course.
EDIT : It seems estren is not a natural metabolite of nandrolone, in vitro and in vivo it converts almost completely to nandrolone, irreversibly. The time-frame of the effects as well as the required AR binding needed for the estrogenic effects in the last study presented seem to therefor indicate that nandrolone is in fact the mediator for the estrogenic effects via the AR perceived with estren. Estren converts entirely to nandrolone, nandrolone binds the AR and the AR homodimer activates estrogen response elements, with and activity 3 times larger than natural androgens, accounting for the unexplicable estrogenic effects perceived with nandrolone, quantified in the first study at roughly 60% that of estradiol
(1)J. Shields-Botella, I Duc, E. Duranti, F. Puccio, P. Bonnet, R. Delansorne, J. Paris. An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. Journal of Steroid Biochemistry & Molecular Biology 87 (2003) 111-122.
(2) J. Botella,t E. Duranti, V. Viader, I. Duc, R. Delansorne, J. Paris. Lack of Estrogenic Potential of Progesterone- or 19-Nor-progesterone-derived Progestins as Opposed to Testosterone or 19-Nor- testosterone Derivatives on Endometrial Ishikawa Cells. Steroid Biochem. Molec. Biol. Vol. 55, No. 1, pp. 77-84, 1995.
(3) Centrella M, McCarthy TL, Chang WZ, Labaree DC, Hochberg RB.Estren (4-estren-3alpha,17beta-diol) is a prohormone that regulates both androgenic and estrogenic transcriptional effects through the androgen receptor.Mol Endocrinol. 2004 May;18(5):1120-30. Epub 2004 Feb 5.