PARENT SESSION
Follicular Development

EXPRESSION OF ANDROGEN RECEPTOR AND APOPTOSIS DURING RAT FOLLICULAR DEVELOPMENT.

Clemens, Jeffrey ¹, Ursu, Stefania¹, ¹

ABSTRACT- Androgen receptor protein (AR) is expressed within the ovary of many mammalian species, including rats. In rats, androgens reportedly promote follicular atresia and decrease ovarian weight. As a potential mediator of follicular development, hormonally and developmentally regulated ovarian expression of AR may have important physiological and pathophysiological consequences. We have used a model of follicular development, the hormonally-primed immature female rat, to examine the expression and regulation of ovarian androgen receptor, along with expression of the NF-b transcription family member p65 and a marker of apoptosis, terminal deoxynucleotidyl transferase (TdT) dUTP end-label (TUNEL) staining. NF-B proteins regulate AR gene expression in the liver and the testes, as well as in a rat granulosa cell line. Modification of the N-terminal of steroid receptors can alter their trans-activation potential. We hypothesized that differences in N-terminal androgen receptor isoform expression might be associated with follicular atresia via apoptosis. Immunohistochemical techniques were used on paraffin-embedded ovaries harvested from human Chorionic Gonadotropin (hCG) treated female rats at three time points: 0, 24 and 48 hours after initiation of treatment. Differential expression of N-terminal AR isoforms was assessed using antibodies directed against the first 20 amino acids of the N-terminal (AR N-20) or against the last 19 amino acids of the C-terminal (AR C-19). N-terminal AR epitope expression was primarily restricted to granulosa cells and decreased as follicular development advanced. The C-terminal AR epitope expression was also present in the thecal and stromal compartments and did not change appreciably during follicular development. Using a p65 specific antibody for immunolocalization, p65 was present in the theca cells and ovarian stroma associated with all stages of follicular development. However, p65 expression in granulosa cells was detectable primarily in early stages of follicular development. Using TUNEL staining as a marker of apoptosis and serial section of ovarian follicles, follicular atresia appears to be correlated with expression of an N-terminal isoform of the androgen receptor. (Supported by NIH HD35330 to JWC)

KEY WORDS: androgen receptor, follicle, ovary, apoptosis