Strange Steroids #2: 17-Deoxysteroids

The next addition to the “strange steroids” series focuses on a couple of steroids possessing anabolic and/or androgenic activity despite the lack of a 17b-hydroxyl function.

17b-hydroxyl group in testosterone (circled).

Testosterone, with the 17b-hydroxyl group circled.

The 17b-hydroxyl group is the most fundamental commonality between steroids that attach to and activate the androgen receptor, with all commercialised anabolic steroids either containing, or being metabolized to, a steroid that contains a 17b-OH.

“Without any doubt, the attachment of the steroid to the receptor at the 17-hydroxyl group is one of the most important attachments. The presence of oxygen in the form of a 17b-hydroxyl group is more important than the presence of oxygen at carbon-3 and for practical purposes all useful anabolic agents and highly active androgens possess the 17b-hydroxyl group.” [1]

The key to the significance of this function is hydrogen bonding, an important feature in ligand-receptor interactions. The Asn705 and Thr877 residues of the androgen receptor form hydrogen bonds with the 17β hydroxyl, locking the steroid into the ligand binding pocket of the receptor. [2] Modification or elimination of the 17β hydroxyl typically ablates anabolic and androgenic action, but not in every case.
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