Transferrin in the developing ovarian follicle: evidence for de-novo expression by granulosa cells

Transferrin is produced primarily by the liver and is best known as a carrier of iron in the circulation. Transferrin is also produced extra-hepatically where it may serve to suppress the generation of reactive oxygen species and act as a growth factor, in addition to its role in the endocytosis of iron. There is evidence that transferrin and its cognate receptor are important for successful development of follicles but little is known about their precise roles in this context. To learn more about their modus operandi, we undertook immunocytochemical studies which revealed that transferrin and its receptor are distributed heterogeneously in human granulosa cells, with more pronounced expression in more mature follicles. Expression within the oocyte itself was not prominent until the antral stage of development. Using nested reverse trancription-polymerase chain reaction (RT-PCR), transferrin mRNA expression was demonstrated in granulosa cells of the human and mouse ovary but not in the oocyte. Hence it appears that local production of transferrin is possible in addition to the likely uptake of circulating protein into the follicle by endocytosis. Values of transferrin in the follicular fluid were found to be highly correlated with those in serum, suggesting that the small contribution made by its localized synthesis in the granulosa cell may be important for some as yet unknown mechanism in follicle maturation.