(2) It was found that the induction of experimental cryptorchidism in the rat produced a marked increase in protein labeling in each of the remaining cells of the germinal epithelium. It would seem that this increase in protein labeling of the cryptorchid testis is due to both an unmasking of the remaining cell types with a higher capacity for protein synthesis as well as to a temperature-induced stimulation of protein synthesis occurring in these same testicular cell types.

(3) The data of the present experiments also indicate that the in vitro inhibition of rat testicular protein labeling caused by temperatures higher than the normal scrotal temperature of 32 C can be protected against by the addition of glucose. The possibility therefore exists that temperatures above 32 C result in irreversible damage to the testicular protein synthesizing systems of the spermatids in the absence of an adequate supply of glucose.

(4) The present experiments indicate that the enzymatic systems involved in the incorporation of lysine into protein of the testis, and especially those found in the spermatids, are markedly more sensitive to the addition of exogenous glucose than those of a number of other tissues of the rat. It is suggested that one possible explanation for the damaging effects of diabetes on testicular germinal epithelium may involve this extremely sensitive regulation of testicular protein synthesis by glucose.

(5) The presently observed sensitive relationship that exists between testicular protein synthesis and glucose may yet have additional clinical bearing. Since glucose is capable of protecting testicular protein labeling against the deleterious effects of an increased temperature, glucose or some of its metabolites may play an important role in the reversal of the degeneration of spermatogenesis occurring in cryptorchidism, pyrexia, or after the use of drugs capable of producing testicular damage as an untoward side effect. In addition, because of the marked dependency of testicular protein synthesis on glucose, it may be possible to utilize a glucose analogue in the continuing search for a clinically useful birth-control drug to be used in the male. The finding that protein synthesis in the mature spermatids has been shown to have the greatest requirement for glucose has special significance since a glucose analogue might suppress spermatogenesis, yet not affect those more immature cells which are responsible for cell renewal. This then would theoretically permit such a male contraceptive drug to be fully reversible.

(6) It is therefore possible to state at the present time that while the spermatids seem to be characterized by a great dependency on glucose utilization for both their morphological integrity and their extent of protein synthesis, the spermatogonia and primary spermatocytes responsible for cell renewal are characterized by a much greater degree of protein synthesis and nucleic acid anabolism which does not appear to be dependent upon glucose utilization. Any difference in the metabolism of those cells of the spermatogenic cycle responsible for cell proliferation and cell renewal as compared to the more mature spermatids may have importance in investigations on spermicidal agents as well as for investigations dealing with enhancement of spermatogenesis in cases of male infertility. Moreover, these metabolic differences may have importance in investigating potential side effects of drugs affecting proliferating germinal cell systems with a possible resulting damage to genetic material causing congenital malformations.

(7) The data obtained on the effects of nitrofurazone and testosterone on testicular metabolism appear to emphasize the desirability of investigating other drugs as well as environmental poisons in a similar biochemical fashion employing testicular slices. The parameters of testicular metabolism discussed in the present paper seem applicable as beginning screening tests to investigate the potential biochemical side effects of a large number of drugs and poisons on spermatogenesis. Such experiments are now being initiated in our laboratory in the hope of further elucidating the biochemical pharmacology of spermatogenesis.