PARENT SESSION

(M742) EXPRESSION OF PDGF LIGANDS AND RECEPTORS IN THE FOLLITROPIN RECEPTOR KNOCKOUT (FORKO) MOUSE OVARY: REGULATION BY FSH AND ESTRADIOL.

Chen, XinLei¹, Aravindakshan, Jayaprakash ¹, Yang, Yinzhi¹, T Pandey , Rashmi ¹, Sairam, M Ram ¹, ¹ Clinical Research Institute of Montreal, Montreal, QC, Canada

ABSTRACT- Although PDGF family members play a vital role in cell motility, proliferation, and chemotaxis via activation of structurally similar - and -receptors little is known of their function in ovarian regulation. We hypothesize that FSH-R signaling may exert its effects partly by regulation of PDGF family. Initial microarray analysis of immature wild type and FORKO ovaries revealed differential expression of both ligands and receptors of this family. To further investigate the hormonal regulation of PDGF family members, we used Affymetrix microarray, RT-PCR, Q-PCR, immunohistochemistry as well as Western Blot. We demonstrate that while PDGF-C and PDGF R increased, PDGF R mRNA levels decreased significantly in the absence of FSH-R signaling. To analyze the mechanism of hormonal regulation of PDGF, ovaries were collected 12, 24 and 48 hrs after administration of eCG or 17 estradiol to immature mice. While PDGF-C and PDGFR- decreased, PDGF-R was not affected after administration of eCG. Administration of estradiol decreased PDGF and their receptors. Interestingly while PDGFR- mRNA did not change in response to PMSG, it decreased after treatment with E2. To further probe the differential regulation of PDGF family members by eCG and estradiol, we co-administered eCG with E2 antagonist, ICI 182,780. PDGF-R was increased suggesting that FSH signalling could increase PDGFR- mRNA only in the absence of estradiol. This can explain in part its increase in our FORKO model. PDGF-C expression decreased in response to both eCG and E2. As the ICI 182,780 given with eCG also decreased PDGF-C expression a mechanism independent of E2 is likely to be involved. During the estrous cycle PDGF-C, PDGF-D and PDGFR- mRNA were found to be highest at proestrous, confirming the complex interplay by FSH and E2. By IHC, we report for the first time the localization of PDGF-C, PDGFR and protein in the mouse ovary. Immunostaining of PDGF-Rs increased as the follicle developed to preantral stage and declined thereafter. Western blot revealed the same trend as mRNA expression. Thus FSH modulates PDGF family members, partly via E2, suggesting that aberrant FSH-R signalling may lead to imbalance of PDGF family which in turn may play a role in abnormal follicle development and eventual ovarian tumorigenesis in FORKO mice (Supported by NCIC & CIHR).

KEY WORDS: PDGF, FSH, estrogen, ovary