Estrogen and estrogen receptor-{beta} (ER{beta})-selective ligands induce galanin expression within gonadotropin hormone-releasing hormone-immunoreactive neurons in the female rat brain.
Among the many factors that integrate the activity of the GnRH neuronal system, estrogens play the most important role. In females, estrogen, in addition to the negative feedback, also exhibits a positive feedback influence upon the activity and output of GnRH neurons to generate the preovulatory LH surge and ovulation. Until recently, the belief has been that the GnRH neurons do not contain estrogen receptors (ERs) and that the action of estrogen upon GnRH neurons is indirect involving several, estrogen-sensitive neurotransmitter and neuromodulator systems that trans-synaptically regulate the activity of the GnRH neurons. Based on our recent findings that GnRH neurons of the female rat coexpress galanin, that galanin is a potent GnRH-releasing peptide, and that ERbeta is present in GnRH neurons, we have evaluated the effect of 17beta-estradiol and two ERbeta-selective agonists (WAY-200070, WAY-166818) on the expression of galanin within GnRH neurons. By combining immunocytochemistry for GnRH and in situ hybridization histochemistry for galanin, we demonstrate that 17beta-estradiol (20 mug/kg, sc) stimulates galanin expression within GnRH-immunoreactive neurons in a time-dependent manner. A significant increase was observed 2 h after its administration to ovariectomized rats. However, a more robust expression required 3-d treatment regimen. Treatment with the beta-selective ligands resulted in similar observations, although no statistical analysis is available for the 2 hr survival. These observations strongly suggest that estrogen and the ERbeta-selective ligands stimulate galanin expression within GnRH neurons via ERbeta, although an indirect mechanism via interneurons still cannot be ruled out.
Merchenthaler
Istvan
I
Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, 10 South Pine Street, MSTF Room 900F, Baltimore, Maryland 21201, USA. imerchem@epi.umaryland.edu
Hoffman
Gloria E
GE
Lane
Malcolm V
MV
D000818:Animals; D000906:Antibodies; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism*; D005260:Female; D019004:Galanin / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D008024:Ligands; D009474:Neurons / Q000378:metabolism*; D010052:Ovariectomy; D011301:Preoptic Area / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D047629:Estrogen Receptor beta; D008024:Ligands; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D019004:Galanin