Endocrine Abstracts (2010) 22 P478

The polymorphic Alu1 variant of ER may modulate the feedback regulation of LH secretion

Katerina Saltiki1, Emily Mantzou1, Eleni Anastasiou1, Theodora Pappa1, Ilpo Huhtaniemi2 & Maria Alevizaki1

1Endocrinology, Metabolism and Diabetes Unit, Evgenidion Hospital and Department of Medical Therapeutics, ALEXANDRA Hospital, Athens University School of Medicine, Athens, Greece; 2Imperial College London, Institute of Reproductive and Developmental Biology, Hammersmith Campus, London, UK.

A common polymorphism of the ERβ gene (AluI) located in 3′-UTR of exon 8 has been shown to be associated with clinical features of altered estrogen action in tissues where this gene is expressed. It has recently been shown that GnRH neurons express ERβ, indicating that this receptor may participate in the feedback regulation of gonadotrophin secretion. We therefore studied the association of gonadotrophin levels and the AluI polymorphism of ERβ in a group of postmenopausal women. Genomic DNA was studied by RFLP in 96 postmenopausal women. LH, estradiol, testosterone and DHEA-S levels were estimated. 33 women were homozygous for the wild type (WT) variant, 53 were heterozygous carriers (carr) and 10 women were homozygous (homoz) for the polymorphic AluI ERβ gene variant. Mean estradiol levels were: WT, 13.8±2.2 (S.E.M.); carr, 12.1±1.6; homoz, 9.3±2.1 (NS). Mean LH levels were significantly higher in carriers of the polymorphic variant: WT, 31.7±2.6; carr, 36.4±2.7; homoz, 45.5±10.46 (P=0.014, ANOVA). There were no significant differences in BMI or the levels of DHEA-S or testosterone between the three groups of polymorphic variants. No differences were observed in the mean LH levels according to the presence of the PvuII polymorphic variant of ERα in the same population. These findings, if confirmed in a larger population sample, provide further evidence that ERβ participates in the feedback regulation of LH secretion. Whether the mechanism is by enhancing the positive feedback or suppressing the negative feedback remains to be determined.

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