The
lactate dehydrogenase (LDH) has been studied widely because it exists in various isozymic forms. The association of A and B subunits of LDH can generate five tetrameric
isozymes, but the finding of the sixth
isozyme in mature human testis and sperm indicated the presence of an additional subunit of LDH, designated as
LDH-X (also termed LDH-C4 due to tetrameric nature of C-subunit).
LDH-C4 isozyme is an iso-, allo-, and auto-
antigen present in mammalian sperm cells. The synthesis of
LDH-C4 in the testis takes place during sexual maturation, and it is the predominant fraction in mature spermatozoa. Though, originally considered to be testis specific,
LDH-C or Ldh3 in mice was later detected in the murine oocyte and early embryo. Ldh3 in mouse supports its role in energy production in spermatids that favor
lactate as substrate and in spermatozoa with a characteristic aerobic glycolytic path to yield
ATP. During last two decades,
cancer/testis-associated genes (CTAs) which are expressed only in the germinal epithelium of the testis are also expressed in some
cancer cells, but not in non-cancerous somatic tissues. The CTAs are considered promising candidates for diagnosis and
immunotherapy of
cancer. The sperm-specific
Ldh-c gene has been shown to express in a broad spectrum of human
tumors, with high frequency in
lung cancer,
melanoma, and
breast cancer; the
protein being expressed virtually in all
tumor types tested. Accordingly,
LDH-C4 is the unique target for
contraception in both males and females and offers potential future for
immunotherapy of different types of
cancers. As
LDH-C has a preference for
lactate as a substrate,
LDH-C activation in
cancer may depend on
lactate for
ATP production. The major aim of this article is to review the salient features of
LDH-C subunit and the immune responses of
LDH-C4 in homologous and heterologous species in relation to its role in acceptance or rejection of the allograft and its application in
contraception and
immunotherapy of
cancer, directly or indirectly through the regulation of its substrate, the
lactate.