Critical role for estrogen receptor alpha in negative feedback regulation of gonadotropin-releasing hormone mRNA expression in the female mouse.
Estrogen exerts an important regulatory influence upon the functioning of the gonadotropin-releasing hormone (GnRH) neurons. Whether this is mediated by estrogen receptor alpha (ERalpha) or ERbeta or both ERs is presently unclear. Using female mice with targeted disruptions of ERalpha and ERbeta (alphaERKO and betaERKO, respectively) we have investigated the in vivo role of the two ERs in the negative feedback influence of estrogen upon GnRH mRNA expression. Compared with intact wild-type mice, plasma luteinizing hormone (LH) levels were substantially (p < 0.01) higher in intact alphaERKO females and increased modestly (p < 0.05) in intact betaERKO mice. Three weeks after ovariectomy, LH concentrations were elevated significantly in wild-type (p < 0.01) and betaERKO (p < 0.05) mice but not changed in alphaERKO females. Quantitative analysis of GnRH mRNA expression using in situ hybridization revealed that cellular GnRH mRNA content was greater (p < 0.05) in intact alphaERKO mice compared with intact wild-type and betaERKO mice. Following ovariectomy, GnRH mRNA expression was elevated in wild-type (p = 0.06) and betaERKO (p < 0.05) females but not alphaERKO mice. These data demonstrate that both ERalpha and ERbeta are involved in inhibiting LH levels at times of estrogen-negative feedback in vivo. However, only ERalpha appears to be critical for the estrogen-negative feedback suppression of GnRH mRNA expression in the female mouse.
Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, UK.
Amber A
AA
Dorling
Martin G
MG
Todman
Kenneth S
KS
Korach
Allan E
AE
Herbison
D000704:Analysis of Variance; D000818:Animals; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone