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

Gonadotropin subunit mRNA expression is differentially regulated durin g the 4-day estrous cycle in rats, with LH-beta and FSH-beta mRNA expr ession rapidly increasing on proestrus. Studies in an ovariectomized ( OVX) GnRH-deficient female rat model have shown that GnRH pulses can i ncrease alpha and FSH-beta mRNA concentrations, but LH-beta mRNA is un changed. Thus, the factors required for physiologic regulation of the LH-beta gene are not fully understood. To determine whether or not the proestrous ovarian hormone environment is required to allow increased expression of the LH-beta gene, GnRH pulses were administered to GnRH -deficient (phenoxybenzamine-treated) intact female rats on proestrus, Both LH and FSH secretion and alpha and FSH-beta mRNA concentrations were increased, but LH-beta mRNA expression was unaltered, The effect of co-administration of GnRH and specific neurohormones (GnRH-associat ed peptide [GAP], galanin, neuropeptide-Y [NPY], and thyrotropin-relea sing hormone [TRH]) was also examined in OVX rats receiving estradiol (E(2)) and progesterone (P) replacement. Alpha and FSH-beta mRNA conce ntrations increased 2-fold in response to pulsatile GnRH, and no furth er increase was seen after the addition of GAP, galanin, or TRH. It wa s of interest that NPY blocked the GnRH-induced rise in alpha and FSH- beta mRNA. LH-beta mRNA expression was not increased by GnRH pulses al one or by addition of any of the neuropeptides. Further studies determ ined that continuous GnRH was no more effective than pulsatile GnRH in stimulating a rise in LH-beta mRNA. The results indicate that GnRH pu lses are not sufficient to enhance LH-beta mRNA expression in the GnRH -deficient female rat. These findings suggest that other, as yet unide ntified, factors are required to produce increases in LH-beta mRNA exp ression seen on the afternoon of proestrus.