Anabolic Steroid Bolandiol For prevent the Loss of Lean Body Mass and Bone Mineral Density

Anabolic Steroid Bolandiol For prevent the Loss of Lean Body Mass and Bone Mineral Density

Bolandiol​ Introduction:

Bolandiol (19-nortestosterone 3β,17β-diol; 4-estren-3β,17β-diol; 3β-dihydronandrolone) is a synthetic anabolic steroid that until recently was available as a dietary supplement used by athletes to enhance performance. Previously, we compared the activity of bolandiol in a castrated adult male Sprague Dawley rat model to that of 19-nortestosterone (19-NT: nandrolone), a proposed metabolite of bolandiol [2] and dihydrotestosterone (DHT), all administered in Silastic implants.

Long-term administration of bolandiol (20-24 wk) prevented the loss of lean body mass (LBM), bone mineral density (BMD), and levator ani (LA) muscle weight that occurs in castrate rats while inhibiting gonadotropin and endogenous T production. The effects of bolandiol were dose-dependent and similar to those observed after administration of DHT or 19-NT to castrate animals. On the contrary, bolandiol resulted in little or no stimulation of ventral prostate (VP) or seminal vesicles (SV) weights at these doses. Thus, bolandiol exhibited tissue selectivity in vivo with a pharmacodynamic profile suitable for potential development as a male contraceptive or a “prostate-sparing” androgen in which suppression of endogenous T might be desirable.

Since bolandiol demonstrated some degree of tissue selectivity with long-term administration, we wanted to further characterize its mechanism of action. In the present study, the potency of bolandiol in various in vitro assays was compared with the potencies of T, DHT, and 19-NT. We determined the relative binding affinity (RBA) of these androgens for various classes of steroid hormone receptors as well as their functional activity in transactivation assays mediated by these receptors. The comparative androgenic/anabolic potency in vivo was evaluated using stimulation of sex accessory glands and LA muscle weights and suppression of gonadotropin secretion as endpoints in the immature castrate male rat. The possibility that bolandiol manifests estrogenic activity in vivo was investigated in the immature female rat by assessing dose-dependent increases in uterine weight following bolandiol or 17β-estradiol (E2) treatment.

Finally, metabolism of bolandiol could play a role in the selectivity of its in vivo activities. It has been suggested that the anabolic activity of bolandiol is attributable to its conversion by 3β-hydroxysteroid dehydrogenase (3β-HSD) to 19-NT [2,4-6], a potent anabolic steroid [7-9], because increased urinary metabolites of 19-NT can be measured after oral dosing of men with bolandiol [10-12]. Interestingly, the prohormone of 19-NT, 19-norandrostenedione, has recently been shown to have tissue selectivity in castrate male rats [13] supporting the notion that precursors and metabolites of these steroids may have unique profiles of tissue activity. Furthermore, by analogy to the major pathways by which T is metabolized, bolandiol could also be converted to tetrahydronandrolone (5α-estran-3β,17β-diol) by 5α-reductase or to E2 by aromatase which might contribute to bolandiol’s ability to maintain BMD in castrate adult rats [3]. Therefore, we examined the potential metabolism of bolandiol by 5α-reductase in vivo and the possible conversion of bolandiol to E2 by purified recombinant human aromatase in vitro.

Abstract:

Bolandiol is a synthetic anabolic steroid that increases lean body mass and bone mineral density without significantly stimulating the sexual accessory glands of adult male rats.

Since bolandiol inhibits the production of gonadotropin and endogenous testosterone (T), we investigated its mechanism of action. We compared the efficacy of boranediol with T,5α-dihydrotestosterone (DHT), 19-nortestosterone (19-NT) and estradiol (E(2)) in vitro and in vivo.

Compared with other androgens, Bolandiol has lower affinity for recombinant androgen receptor (AR), and recombinant human progesterone receptor (PR-A, PR-B) and estrogen receptors (ERalpha and β-) 1) has low but measurable affinity. ). Functional agonist activity is assessed in AR, PR or ER mediated transcription assays.

Bolandiol is irritating in all of these assays, but only 4-9% is as effective as T, DHT and 19-NT AR, with 1% efficacy comparable to PR progesterone, 3% and 1% Efficacy was effective with E(2) via ERalpha or ERbeta, respectively. In immature ovariectomized rats, bolandiol is equivalent to T in stimulating the growth of levator ani muscle, but not as effective as T in stimulating accessory gland growth. Bolandiol also stimulated an increase in uterine weight in immature female rats, which was not partially blocked by ICI 182,780, but was not aromatized in vitro by recombinant human aromatase.

Simultaneous treatment with the dual 5α-reductase inhibitor dutasteride did not inhibit bolandiol's stimulation of the sex glandular weight compared to T. Since bolandiol exhibits tissue selectivity in vivo, it may act through AR, PR and/or ER.

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