While it had been clear for many centuries that the testicles were crucial for the male body to properly develop, it was not until modern times that an understanding of testosterone began to form. The first solid scientific experiments in this area, which eventually led to the discovery and replication of testosterone (and related androgens), were undertaken in the 1800s. During this century a number of animal experiments were published, most of which involved the removal and/or implantation of testicular material from/in a subject. Although very crude in design by today's standards, these studies certainly laid the foundation for the modern field of endocrinology (the study of hormones). By the turn of the century, scientists were able to produce the first experimental androgen injections. These were actualized either through the filtering of large quantities of urine (for active hormones), or by extracting testosterone from animal testicles. Again, the methods were rough but the final results proved to be very enlightening.
Chemists finally synthesized the structure of testosterone in the mid-1930’s, sparking a new wave of interest in this hormone. With the medical community paying a tremendous amount of attention to this achievement, the possible therapeutic uses for a readily available synthetic testosterone quickly became an extremely popular focus. Many believed the applications for this type of a medication would be extremely far-reaching, with uses ranging from the maintenance of an androgen deficiency, to that of a good health and wellbeing treatment for the sickly or elderly. During the infancy of such experimentation, many believed they had crossed paths with a true “fountain of youth.”
Dihydrotestosterone and nandrolone, two other naturally occurring steroids, were also isolated and synthesized in the early years of steroid development. To make things even more interesting, scientists soon realized that the androgenic, estrogenic, and anabolic activity of steroid hormones could be adjusted by altering their molecular structure. The goal of many researchers thereafter became to manufacture a steroid with extremely strong anabolic activity, but will display little or no androgenic/estrogenic properties. This could be very beneficial, because side effects will often become pronounced when steroid hormones are administered in supraphysiological amounts. A “pure” anabolic would theoretically allow the patient to receive only the beneficial effects of androgens (lean muscle mass gain, increased energy and recuperation, etc.), regardless of the dosage. Some early success with the creation of new structures convinced many scientists that they were on the right track. Unfortunately none of this progress led researchers their ultimate goal. By the mid-1950’s, well over one thousand testosterone, nandrolone, and dihydrotestosterone analogues had been produced, but none proved to be purely anabolic compounds.
The failure to reach this goal was primarily due to an initial flawed understanding of testosterone's action. Scientists had noticed high levels of DHT in certain tissues, and believed this indicated an unusual receptor affinity for this hormone. This led to the belief that the human body had two different androgen receptors. According to this theory, one receptor site would respond only to testosterone (eliciting the beneficial anabolic effects), while the other is activated specifically by the metabolite, dihydrotestosterone. With this understanding, eliminating the conversion of testosterone to DHT was thought capable of solving the problem of androgenic side effects, as these receptors would have little or none of this hormone available for binding. More recently, however, scientists have come to understand that only one type of androgen receptor exists in the human body. It is also accepted that no anabolic/androgenic steroid can possibly be synthesized that would participate only with receptors in tissues related to anabolism. DHT, which was once thought not to bind to the same receptor as testosterone, is now known to do so at approximately three to four times the affinity of its parent, and the unusual recovery of DHT from androgen responsive tissues is now attributed to the distribution characteristics of the 5a-reductase enzyme.
Wlliam Llewellyn (2011) - Anabolics