Regulation of gonadotropin subunit messenger ribonucleic acid expression in gonadotropin-releasing hormone (GnRH)-deficient female rats: Effects of GnRH, galanin, GnRH-associated peptide, neuropeptide-Y, and thyrotropin- releasing hormone

Abstract

Gonadotropin subunit mRNA expression is differentially regulated during the 4-day estrous cycle in rats, with LH-β and FSH-β mRNA expression rapidly increasing on proestrus. Studies in an ovariectomized (OVX) GnRH deficient female rat model have shown that GnRH pulses can increase alpha and FSH-β mRNA concentrations, but LH-β mRNA is unchanged. Thus, the factors required for physiologic regulation of the LH-β gene are not fully understood. To determine whether or not the proestrous ovarian hormone environment is required to allow increased expression of the LH-β gene, GnRH pulses were administered to GnRH-deficient (phenoxybenzamine-treated) intact female rats on proestrus. Both LH and FSH secretion and alpha and FSH-β mRNA concentrations were increased, but LH-β mRNA expression was unaltered. The effect of co-administration of GnRH and specific neurohormones (GnRH- associated peptide [GAP], galanin, neuropeptide-Y [NPY], and thyrotropin- releasing hormone [TRH]) was also examined in OVX rats receiving estradiol (E2) and progesterone (P) replacement. Alpha and FSH-β mRNA concentrations increased 2 fold in response to pulsatile GnRH, and no further increase was seen after the addition of GAP, galanin, or TRH. It was of interest that NPY blocked the GnRH-induced rise in alpha and FSH-β mRNA. LH-β mRNA expression was not increased by GnRH pulses alone or by addition of any of the neuropeptides. Further studies determined that continuous GnRH was no more effective than pulsatile GnRH in stimulating a rise in LH-β mRNA. The results indicate that GnRH pulses are not sufficient to en hence LH-β mRNA expression in the GnRH-deficient female rat. These findings suggest that other, as yet unidentified, factors are required to produce increases in LH- β mRNA expression seen on the afternoon of proestrus.