Regulation of pituitary alpha-subunit, beta-luteinizing hormone and prolactin messenger ribonucleic acid by gonadotropin-releasing hormone and estradiol in hypogonadal mice.

We have investigated the effects of three different GnRH injection regimens and the effects of estradiol benzoate (EB) on expression of the common alpha-subunit, beta-LH, and PRL genes in male and female hpg mice. GnRH was injected once daily (100 ng), every 2 h (100 ng) or every 30 min (25 ng), and EB (10 micrograms) was injected once daily. The effects of continuous exposure to the superactive agonist D-Trp6-GnRH released from microcapsules were also studied. Northern blot analysis showed that administration of GnRH increased alpha-subunit mRNA levels 2- to 10-fold in male and female hpg but not normal mice and had no significant effect on beta-LH or beta-TSH mRNA levels. The greatest increase in alpha-mRNA occurred when 100 ng GnRH were injected every 2 h and could be detected within 6 h of the first GnRH injection. More frequent injections (25 ng every 30 min) were less effective in increasing alpha-mRNA, as was prolonged exposure to the D-Trp6-GnRH superagonist. The increase in alpha-mRNA was associated with an increase in pituitary FSH content of similar magnitude. Continuous exposure of the pituitary gland to D-Trp6-GnRH (approximately 1500 ng/day) resulted in a smaller (2-fold) increase in alpha-mRNA and pituitary FSH content, suggesting that desensitization had occurred. EB had little effect on beta-LH mRNA and did not alter alpha-mRNA levels or affect the increase in alpha-mRNA caused by GnRH. Injection of GnRH every 2 h increased pituitary PRL mRNA levels in female but not male hpg mice, probably due to an indirect effect resulting from increased estrogen secretion. We conclude that GnRH administration to hpg mice significantly increases alpha-subunit but not beta-LH mRNA levels and that maximal effects occur with 100 ng GnRH injections every 2 h. Although EB does have direct effects upon pituitary gonadotropin content in hpg mice, the absence of significant changes in alpha- and beta-LH mRNA suggests that these effects may be largely posttranscriptional.