Anovulation is the leading cause of female infertility, therefore it is essential to identify the mechanisms regulating ovulation to gain insight into the underlying causes of female infertility and develop novel therapeutic interventions. Progesterone receptor (PGR), a steroid-dependent transcription factor expressed in ovarian granulosa cells, is obligatory for ovulation in mammals. We investigated effector pathways activated by PGR in order to identify those that are crucial for oocyte release. We hypothesised that PGR may upregulate ATP production to fuel ovulatory processes. To address this we investigated major metabolic pathways (mitochondrial function, glycolysis and fatty-acid oxidation) in granulosa cells of mice null for PGR (PRKO). Using real-time cell metabolism assays we found that surprisingly ATP production via mitochondrial respiration or glycolysis was not PGR-regulated. Supporting these observations, treatment of mice with rotenone, an inhibitor of Complex I reduced granulosa cell mitochondrial respiration but this did not impair ovulation. In parallel, we performed RNA-seq analysis of both isolated granulosa cells and the GC-depleted ovarian stromal tissue to identify differentially expressed genes in PRKO vs WT mice. Ingenuity Pathways Analysis elucidated a number of interesting pathways that were dysregulated in the two ovarian cell compartments. Of note, ‘lipid metabolism’ was dysregulated in granulosa cells of PGR-null mice, and a network of adipose-related transcription factors, Bcl11b, Pparg, Hnf4a and Zbtb16, was identified as PGR-regulated with gene expression induced during ovulation. Additionally, Cpt1a and Cpt1b, the rate-limiting enzymes for fatty-acid oxidation were PGR-regulated in granulosa cells. These findings advance our understanding of steroid-receptor regulation of metabolism, demonstrating that PGR does not regulate mitochondrial respiration or glycolysis in granulosa cells but activates alternative pathways for lipid regulation during ovulation. Additionally, RNA-seq analysis of both granulosa and stromal cells has revealed intriguing PGR-regulated gene networks that shed light on the intercellular mechanisms regulating ovulation.