Hence, in the present work, we investigated (i) gene and protein expression of SPX and GALR2/3 in GC of normal weight and obese healthy women and diagnosed with PCOS, its immunolocalization in the human ovary, as well as SPX levels in FF; (ii) the in vitro effect of SPX on GC proliferation and steroidogenesis; and (iii) the molecular mechanism of SPX action by GALR2/3 silencing and pharmacological inhibition of kinases: MAP3/1, AKT, and protein kinase A (PKA), as well as signal transducer and activator of transcription 3 (STAT3). This evidence concerns the gene STAT3 and polycystic ovary syndrome.