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Division of Endocrinology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908
Address all correspondence and requests for reprints to: Dr. Alan C. Dalkin, University of Virginia Health Sciences Center, Division of Endocrinology, Department of Internal Medicine, 5041 MR4 Building, Lane Road, Charlottesville, Virginia 22908. E-mail acd6v{at}virginia.edu
GnRH is the primary stimulus in the regulation of gonadotropin subunit mRNA expression. Additionally, local (pituitary) production of activin and follistatin appear to modulate the expression of FSH ß mRNA. The current studies aimed to determine whether GnRH regulation of pituitary activin (ß-B) and follistatin mRNAs could play a role in the differential actions of GnRH pulse pattern on gonadotropin mRNA expression in female rats. In response to altered GnRH pulse amplitude, the expression of FSH ß and follistatin mRNAs followed an inverse pattern. Only high dose GnRH increased expression of follistatin whereas, in contrast, ß-B and FSH ß expression were increased following lower doses of GnRH. To determine whether increased follistatin mRNA expression was correlated with FSH ß mRNA responses, we examined their temporal relationship following high dose GnRH. Both FSH ß and follistatin mRNAs were increased within 2 h and remained increased through 6 h. However, by 12 h FSH ß mRNA levels returned to values seen in controls, suggesting that increased follistatin requires 612 h to reduce FSH ß mRNA. In response to altered GnRH pulse frequency, FSH ß expression was increased at all pulse intervals (8240 min) examined. Rapid GnRH pulse frequencies (8-min intervals) increased follistatin expression, whereas ß-B mRNA was only increased after 30-min pulse intervals, which also resulted in maximal FSH ß mRNA concentrations. These results suggest that changes in pituitary activin (ß-B) and follistatin mRNA expression may be important components of gonadotrope responses to pulsatile GnRH, and potentially imply that GnRH stimulation of activin and follistatin peptide production provides regulatory control over the production of FSH.
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