Hormones: what the testis really sees
Authors: Setchell B. P. 
Published: July 2004

Various barriers in the testis may prevent hormones from readily reaching the cells they are supposed to stimulate, especially the hydrophilic hormones from the pituitary. For example, LH must pass through or between the endothelial cells lining the blood vessels to reach the surface of the Leydig cells, and FSH has the additional barrier of the peritubular myoid cells before it reaches the Sertoli cells. The specialised junctions between pairs of Sertoli cells would severely restrict the passage of peptides from blood to the luminal fluid and therefore to the cells inside this barrier, such as the later spermatocytes and spermatids. There is evidence in the literature that radioactively labelled LH does not pass readily into the testis from the blood, and the concentration of native LH in the interstitial extracellular fluid surrounding the Leydig cells in rats is only about one-fifth of that in blood plasma. Furthermore, after injection with LHRH, there are large rises in LH in the blood within 15 min, at which time the Leydig cells have already responded by increasing their content of testosterone, but with no significant change in the concentration of LH in the interstitial extracellular fluid. Either the Leydig cells respond to very small changes in LH, or the testicular endothelial cells in some way mediate the response of the Leydig cells to LH, for which there is now some evidence from co-cultures of endothelial and Leydig cells. The lipophilic steroid hormones, such as testosterone, which are produced by the Leydig cells, have actions within the seminiferous tubules in the testis but also in other parts of the body. They should pass more readily through cells than the hydrophilic peptides; however, the concentration of testosterone in the fluid inside the seminiferous tubules is less than in the interstitial extracellular fluid in the testis, especially after stimulation by LH released after injection of LHRH and despite the presence inside the tubules of high concentrations of an androgen-binding protein. The concentration of testosterone in testicular venous blood does not rise to the same extent as that in the interstitial extracellular fluid, suggesting that there may also be some restriction to movement of the steroid across the endothelium. There is a very poor correlation between the concentrations of testosterone in fluids from the various compartments of the testis and in peripheral blood plasma. Determination of the testosterone concentration in the whole testis is also probably of little predictive value, because the high concentrations of lipid in the Leydig cells would tend to concentrate testosterone there, and hormones inside these cells are unlikely to have any direct effect on other cells in the testis. The best predictor of testosterone concentrations around cells in the testis is the level of testosterone in testicular venous blood, the collection of which for testosterone analysis is a reasonably simple procedure in experimental animals and should be substituted for tissue sampling. There seems to be no simple way of determining the concentrations of peptide hormones in the vicinity of the testicular cells.