Follicular maturation is a complex process controlled by a wide array of molecules that includes pituitary gonadotropins (FSH and LH) and steroid hormones as well as many other locally produced factors. Angiogenesis is initiated early in follicular development and contributes to folliculogenesis because increased vascularization of individual follicles results in the preferential delivery of gonadotrophins. Thus it is believed that blood flow plays an instrumental role in the selective maturation of preovulatory follicles and eventually ovulation. The pituitary hormones FSH and LH are major regulators of angiogenesis in the ovary, as they increase bFGF (basic fibroblast growth factor) and VEGF (vascular epithelial growth factor), important members of the vascular-specific angiogenic factors. Pituitary tumour transforming gene (PTTG) and hypoxia-inducible factor-1α (HIF-1α ) are known as transcriptional activators for βFGF and VEGF in several cell lines and tissues. Using oligonucleotides to prime specific sequences in the PTTG and HIF-1α genes we amplified cDNA obtained from ovarian granulosa cells, from Holtsman Sprague-Dawley rats killed by cervical dislocation, treated with 0.2 mIU of FSH. Both PTTG and HIF-1α, transcriptional activators, are expressed in granulosa cells and FSH increased in a time-dependent manner, reaching the maximum levels (4-fold) at 48 h of stimulation, when granulosa cells acquired a pre-ovulatory phenotype. Since forskolin also induced the mRNA levels of both factors we concluded that this is a cAMP-mediated effect. Using specific inhibitors (KT 5720, PD 98059, SB 203580, GF 109203X, LY 2940021) of different pathways we found that the FSH induction of PTTG and HIF-1α is mediated by PKA, but also by MAPKs. Co-treatment of granulosa cells with GnRH, a well known ovarian atretic factor, prevents FSH mediated increases in PTTG mRNA levels.