Gonadotropin-releasing hormone regulation of gonadotropin subunit gene expression in female rats: Actions on follicle-stimulating hormone beta messenger ribonucleic acid (mRNA) involve differential expression of pituitary activin (beta-B) and follistatin mRNAs

GnRH is the primary stimulus in the regulation of gonadotropin subunit mRNA expression. Additionally, local (pituitary) production of activin and foll istatin appear to modulate the expression of FSH beta mRNA. The current stu dies aimed to determine whether GnRH regulation of pituitary activin (beta- B) and follistatin mRNAs could play a role in the differential actions of G nRH pulse pattern on gonadotropin mRNA expression in female rats. In respon se to altered GnRH pulse amplitude, the expression of FSH beta and follista tin mRNAs followed an inverse pattern. Only high dose GnRH increased expres sion of follistatin whereas, in contrast, beta-B and FSH beta expression we re increased following lower doses of GnRH. To determine whether increased follistatin mRNA expression was correlated with FSH beta mRNA responses, we examined their temporal relationship following high dose GnRH. Both FSH be ta and follistatin mRNAs were increased within 2 h and remained increased t hrough 6 h. However, by 12 h FSH beta mRNA levels returned to values seen i n controls, suggesting that increased follistatin requires 6-12 h to reduce FSH beta mRNA. In response to altered GnRH pulse frequency, FSH beta expre ssion was increased at all pulse intervals (8-240 min) examined. Rapid GnRH pulse frequencies (8-min intervals) increased follistatin expression, wher eas beta-B mRNA was only increased after 30-min pulse intervals, which also resulted in maximal FSH beta mRNA concentrations. These results suggest th at changes in pituitary activin (beta-B) and follistatin mRNA expression ma y be important components of gonadotrope responses to pulsatile GnRH, and p otentially imply that GnRH stimulation of activin and follistatin peptide p roduction provides regulatory control over the production of FSH.