Expression of ER-alpha Isoforms in Periodontal Tissues

Objective: Functional changes in the female reproductive system are well known to be associated with oral manifestations. The incidence of gingivitis and pyogenic granuloma increase during pregnancy; while menopause predisposes to alveolar bone loss due to periodontitis. Although changes in estrogen levels have been postulated to be etiologic factors in these conditions, conflicting reports concerning the presence of estrogen receptors (ERs) in gingiva (G) and/or periodontal ligament (PDL) are found in the literature. Thus, we have re-examined this issue. Experimental Methods: Immunoblot analysis was used to determine relative steady-state levels of ERs in samples of non-inflamed G and PDL obtained from healthy young adults, and in primary cultures of human gingival fibroblasts (hGFs). Expression in cultured cells was also examined by RT-PCR. Results: Both G and PDL contained multiple isoforms of ER-alpha (approx 65, 55 and 40 kDa). However when cultured hGFs were examined, the putative wildtype ER-alpha (65 kDa) was not observed, and only the two alternatively spliced isoforms were expressed. Conclusions: ER-alpha is expressed in human G and PDL and the heterogeneity of isoforms helps explain the previous conflicting reports regarding the presence of ERs in oral tissues and cultured cells. The differences in patterns of isoform expression between whole gingival tissue and cultured fibroblasts suggests that splicing may be regulated by external signals, and may be clinically significant since splice variants are known to exhibit atypical activities. Supported by Baylor Oral Health Foundation and NIH/NIDCR DE07188