The strength in comparison: Franz von Leydig (May 21, 1821 - April 13, 1908).

Abstract

Exciting progress in understanding mammalian sex determination goes way beyond a gene on the Y chromosome (SRY, sex determining region of the Y chromosome) that gets the process of male gonad development started. True, SRY expression starts early in mammals, but it is short-lived, instead passing its main job onto another, more-highly conserved family member, SOX9, which then passes the responsibility further down the line. The rubber hits the road, so to speak, at a small number of cells in the developing testis - the Leydig cells - that are responsible for the majority of testosterone (and its variants) in the male. Testosterone synthesis by Leydig cells is under the control of lutenizing hormone (LH) from the pituitary gland. LH directly increases cholesterol desmolase activity, which converts cholesterol to pregnenolone, an essential precursor of testosterone. First described 165 years ago by Franz von Leydig (1850), in a variety of vertebrates, Leydig cells differentiate as the seminiferous tubules form in the developing testis, and have a unique appearance: From the comparative histology of the testis it is clear that, in addition to seminiferous tubules, blood vessels, and nerves, one finds an additional constant component in the mammalian testis, namely a cell-like mass that when present in smaller amounts follows the course of blood vessels between the seminiferous tubules, but when more developed, becomes a mass in which the seminiferous tubules are embedded. Its main constituents are small granules of fatty appearance, which are unaltered by acetic acid and sodium hydroxide treatment, are colorless, or yellowish, and at least in some mammals the entire granular mass is surrounded by a sharp outline. Also, at times, the entire structural aggregate is of such an appearance that one can speak of it as a complete cell. The published description of these cells by von Leydig was confident and impactful based both on the importance of these cells to the physiology of the male, and on the strength of his comparative analysis. He examined testicular tissue and observed these steroidogenic cells in a variety of non-human primates, bats, insectivores, carnivores, marsupials, rodents, rabbits, pigs, horses, artiodactyls, and a dolphin. Indeed, one of von Leydig's strengths was his comparative approach, which is exemplified by his contributions to multiple areas of biology - e.g. the Leydig organ, which contributes to blood cell formation in cartilaginous fish, and the “other” Leydig cell, a mucus-secreting cell of fish and amphibian larvae. This widespread interest in all animals started early with von Leydig; as a young child, he coveted a makeshift wooden microscope with lenses embedded in folded paper. Histology was an art form, and von Leydig excelled at it. He studied medicine at the University of Würzburg, and upon earning his degree became an assistant in the physiology department where he taught histology and developmental anatomy. His mentors were exceptional investigators who likely had strong impacts on his breadth of research capabilities, including Albert von Kölliker (1817-1905), an outstanding and highly diverse histologist and anatomist who worked with mammals, marine invertebrates, and even arthropods. In 1857, several years after his “testicular cell” study, von Leydig became full professor at the University of Tübingen, where he published the highly influential morphology work Lehrbuch der Histologie des Menschen und der Tiere. In it, Leydig reviewed and integrated crucial developments in the field of histology, including the discovery and definition of the cell by Jan Evangelista Purkyne (1797-1869), Gabriel Gustav Valentin (1810-1883), and Theodor Ambrose Hubert Schwann (1810-1882). This treatise is considered one of the best accounts of the growth of comparative anatomy and histology. von Leydig became professor of comparative anatomy at the University of Bonn in 1875, where he stayed until his death in 1908. Ironically for the namesake of the testicular cells that “father” male development, von Leydig and his wife never had children.