Activin a regulation of gonadotropin-releasing hormone synthesis and release in vitro

Activin is essential for the regulation of normal mammalian reproductive fu nction at both the pituitary and gonadal levels. However, its central actio ns in the control of the hypothalamic-pituitary-gonadal axis remain largely unexplored, The present study aims to determine whether activin could regu late the reproductive axis at the level of the hypothalamus, th rough contr ol of the GnRH neuroendocrine system. Using the GnRH-secreting GT1-7 neuron al cell line as a model system, we demonstrate expression of mRNAs encoding activin receptor types I, IB, and II. We examined the effects of activin A on GnRH protein secretion and mRNA levels in GT1-7 cells. Treatment with r h-activin A regulated both GnRH protein secretion and GnRH mRNA expression in the GT1-7 cells in a time-dependent fashion. Using transient transfectio n assays, we explored a potential transcriptional basis for these changes. Activin A increased reporter gene activity driven by minimal GnRH enhancer and promoter elements, suggesting that activin may regulate GnRH gene expre ssion at the level of transcription. Lastly, activin A treatment of male ra t hypothalami, in vitro, increased GnRH protein secretion. Collectively, mo lecular and physiological evidence support the presence of an activin syste m which might act at a hypothalamic site to regulate mammalian reproduction via activation of GnRH synthesis and release.