PULSATILE GNRH REGULATION OF GONADOTROPIN SUBUNIT GENE-TRANSCRIPTION

We investigated the requirement for gonadotropin-releasing hormone (Gn RH) release in vivo and the pattern of GnRH administration in vitro on the expression of the gonadotropin subunit genes in female rats. Inje ction of the GnRH antagonist ([Nal-Lys] GnRH; 30 ug/100g bw) to ovarie ctomized rats rapidly suppressed transcription of the alpha-subunit an d LH beta genes to 10-25% of control after 24 h, as measured by nuclea r run-off assays. The rate of FSH beta gene transcription was also sup pressed, but to a lesser extent (to 60-75% of control). Administration of 17 beta-estradiol (20 ug/100 g bw) in addition to antagonist did n ot suppress transcription of the genes beyond that seen with the antag onist alone. Administration of constant levels of GnRH (0.1, 1, or 10 nM) to pituitary fragments in static culture stimulated alpha-subunit mRNA synthesis 2- to 3-fold, but had no significant sustained effects on LH beta or FSH beta transcription. In contrast, pulsatile GnRH admi nistered once per hour (25 ng over 10 min) to pituitary fragments moun ted on perifusion columns stimulated both alpha-subunit and LH beta ge ne transcription 3-fold after 3 h, with inconsistent stimulation of FS H beta. Pulsatile GnRH appears to be crucial for LH beta gene stimulat ion, as continuous GnRH on the columns stimulated only alpha-subunit m RNA synthesis. Thus, pulsatile GnRH in vivo is required to maintain tr anscription of the alpha-subunit and LH beta genes, with lesser effect s on FSH beta. While continuous GnRH can stimulate cu-subunit mRNA syn thesis, a pulsatile GnRH is required to stimulate the LH beta gene.