Nandrolone estrogenic via the AR ?
(Big Cat)
Nandrolone estrogenic via the AR ?
Sorry if anyone has adressed this topic of late, i've been busy and not as present as normal, so I may have missed it.

But figured this was interesting enough to post. Old research, only recently published (1) shows demonstrates that nandrolone has an estrogenic value of 60 compared to an arbitrary value of 100 for estradiol. Suggesting that mg for mg, nandrolone is 3/5 as estrogenic as estradiol. Newer research tried to examine the estrogenic value of nandrolone and nandrolone-derivatives (2).

The results in short : 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.

(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.

Originally posted by Nandi
You got me thinking a bit more, Big Cat. Irrespective of which of the above two scenarios is the predominant one, could we cover all bases with a compound the binds to the ERE and renders it unable of initiating transcription. It turns out there is at least one family of compounds with this property:

J Steroid Biochem Mol Biol. 2005 Jul 27; [Epub ahead of print]

Transcriptional inhibition of the estrogen response element by antiestrogenic piperidinediones correlates with intercalation into DNA measured by energy calculations.

Sidell N, Tanmahasamut P, Ewing DE, Hendry LB.

Department of Gynceology and Obstetrics, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.

The energy of interaction of antiestrogenic ligands bound to DNA derived from molecular modeling was compared to the capacity of the ligands to directly inhibit the transcriptional activity of an estrogen responsive gene. 3-Phenylacetylamino-2,6-piperidinedione (A10) and related compounds were intercalated into a partially unwound DNA site in a canonical estrogen response element (ERE). The piperidinedione/ERE complexes were subjected to energy minimization and the strength of interaction of the ligands with the DNA was measured. The ability of the ligands to inhibit transactivation was assessed using a reporter gene constructed with the ERE of the vitellogenin gene promoter (ERE(v)-tk-Luc) transiently transfected into the human estrogen receptor-positive MCF-7 breast cancer cell line. The results demonstrate a direct correlation between the calculated energetic fit of the compounds in the ERE and inhibition of ERE(v) transactivation. The order of potency of the compounds to suppress estrogen-dependent reporter gene activity was identical to that previously shown for inhibiting the growth of MCF-7 cells. To our knowledge, these results provide the first direct experimental evidence that the predicted fit of a class of compounds into a defined DNA binding site correlates with the ability of the compounds to modulate specific gene functions regulated at that site.