Estradiol stimulates preoptic area-anterior hypothalamic proGnRH-GAP gene expression in ovariectomized rats

James L. Roberts, Clive M. Dutlow, Moshe Jakubowski, Mariann Blum, Robert P. Millar

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The decapeptide gonadotropin-releasing hormone (GnRH) and the 56-amino acid GnRH-associated peptide (GAP) are derived from a common precursor translated from the proGnRH-GAP mRNA. Studies using solid-phase hybridization techniques (i.e., Northern blot analysis, dot blot analysis, or in situ hybridization autoradiography) have yielded a controversy as to whether estradiol stimulates, inhibits, or has any effect on proGnRH-GAP gene expression in the preoptic area-anterior hypothalamus (POA-AH) of the ovariectomized (OVX) rat. Using a sensitive and quantitative solution hybridization-nuclease protection assay, which ensures complete hybridization of target RNA to probe RNA, we examined the effects of OVX and estradiol replacement on the amount of proGnRH-GAP mRNA in individual POA-AH dissections. Rats sacrificed at different intervals after OVX showed a significant time-dependent decrease (34-60%) in the levels of POA-AH proGnRH-GAP mRNA relative to sham-operated animals; OVX rats treated with estradiol, however, had proGnRH-GAP mRNA levels comparable to those of sham-OVX animals. To verify these observations, levels of the proGnRH-GAP peptide, measured by radioimmunoassay with antibodies directed against the cleavage and amidation site between the GnRH and the GAP portions of the precursor molecule, were also found to decrease (37%) after OVX and increase (63-85%) following estradiol replacement, relative to intact rats. These data support the view that estradiol stimulates the levels of both proGnRH-GAP mRNA and its primary translation product in the POA-AH region of the OVX rat.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalMolecular Brain Research
Issue number2-3
StatePublished - Nov 1989
Externally publishedYes


  • Estradiol
  • Gonadotropin-releasing hormone-GAP precursor
  • Hypothalamus
  • Ovariectomy
  • Preoptic area
  • Solution hybridization-nuclease protection assay

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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