A History of Leydig Cell Research

Franz Leydig first described the testicular cells in 1850 that now bear his name. For the next 50 yr after their discovery, Leydig cells were the subject of further studies by light microscopy, and diverse speculations were offered about their possible function. In 1903, Pol Bouin and Paul Ancel provided the first substantial evidence that Leydig cells constituted an endocrine gland controlling male secondary sexual characteristics. Their evidence seemed compelling at the time, but was necessarily circumstantial, because there was no direct proof that Leydig cells produced a male hormone. Over subsequent decades, workers found additional evidence that these cells had an endocrine function, but there were also other findings that cast doubt on the hypothesis, and increasing skepticism developed about the earlier evidence. By the late 1920s, many influential reproductive biologists suspected that the seminiferous tubules were the actual source of male hormone. During the 1930s, the male hormone was shown to be testosterone, its endocrine actions were studied extensively, and the role of the pituitary in regulating testicular function was demonstrated. From the 1930s through the 1950s, Leydig cells came back into favor as endocrine cells, although some uncertainty persisted and there was still no direct evidence that Leydig cells produced androgen. Finally, direct evidence came from histochemistry in 1958 and from biochemistry in 1965.