FSH modulatory effect on human granulosa cells: a gene–protein candidate for gonadotrophin surge-attenuating factor

Previous evidence indicates a homology of gonadotrophin surge-attenuating factor (GnSAF) to the carboxyl terminal of human serum albumin (HSA) and the ability of human granulosa cells to produce mRNA transcripts corresponding to this fragment, but the underlying mechanism is still unknown. This study investigated the role of FSH in vitro in the expression of the carboxyl terminal of HSA by human luteinized granulosa cells. Cells were cultured on poly-l-lysine-coated microscope slides in the absence or presence of 10 ng/ml FSH, followed by in-situ hybridization and immunocytochemistry. In the presence of FSH, mRNA transcripts corresponding to the carboxyl terminal of the HSA gene and corresponding protein could be detected in comparable intensity to that seen by hepatic HepG2 cells (positive control). Significantly lower expression was detected in granulosa cells cultured without FSH addition (P < 0.01), but no expression was detected in HeLa cells. These results demonstrate for the first time that FSH stimulates the expression of the carboxyl terminal fragment of the HSA gene and corresponding protein in human luteinized granulosa cells. Therefore, the carboxyl terminal of HSA has a functional role in the ovary and this further supports the notion that this HSA fragment is a GnSAF-bioactive entity.Gonadotrophin surge-attenuating factor (GnSAF) is a nonsteroidal ovarian substance which attenuates the endogenous LH surge in superovulated women. In-vivo and in-vitro evidence has shown that GnSAF is produced under the stimulation of FSH and may play a physiological role during the normal menstrual cycle. We have previously demonstrated that GnSAF has identity to the carboxyl terminal fragment of human serum albumin (HSA). In this study, we investigated the role of FSH on the expression of the carboxyl terminal fragment of HSA by human luteinizing granulosa cells in vitro. It is demonstrated for the first time that FSH stimulates the expression of this fragment of HSA gene and the corresponding protein in human luteinizing granulosa cells. This finding supports further the notion that this fragment of HSA is the GnSAF bioactive entity.