Activin A is a dimeric glycoprotein showing a high sequence homology with transforming growth factor-beta (TGF-beta) and playing autocrine/paracrine actions in reproductive tissues. However, since the synthesis of activin is ubiquitous it may have a role in regulating cell growth and differentiation in several tissues. Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age. The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets. With this purpose human pancreatic islets were incubated with varying concentrations of activin A (0.1 to 10.0 nM). In absence of glucose, activin A did not modify insulin secretion at the different concentrations used. In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern. In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM). Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001). The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.

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Objective: To evaluate the expression of activin bA-subunit mRNA and the secretion of activin A in/from cultured GnRH-secreting neuronal cells cloned from human olfactory epithelium (FNC-B4), which showed biochemical and antigenic properties of GnRH-secreting neurons. Design: FNC-B4 cells were cultured in basal and conditioned media. Methods: Reverse transcription-polymerase chain reaction (RTR±PCR) evaluated the expression of activin bA-subunit mRNA. By using a speci®c ELISA, dimeric activin A concentrations were measured in culture media, in the absence or presence of carvone or forskolin and with different doses of progesterone, GnRH, and estradiol. Results: RT±PCR experiments performed on total RNA isolated from FNC-B4 cells, using speci®c primers for the activin bA gene, showed a 787 bp DNA band corresponding to the bA gene. FNC-B4 cells secreted activin A, and the highest accumulation in conditioned medium was achieved after 3 h culture: the addition of forskolin, but not of carvone, was able to stimulate the release of activin A from cultured neuronal cells (P < 0.01). When progesterone or GnRH was added, a signi®cant accumulation of activin A was observed (P < 0.01), while estradiol administration did not signi®cantly affect activin A secretion. Conclusion: To date, this is the only study, in an in vitro human model reporting, that GnRH-secreting neuronal cells expressed activin bA-subunit mRNA, and released dimeric activin A in culture medium. The expression and secretion of activin suggests that in these cells activin A might exert its action by autocrine/paracrine mechanisms.

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