role of rfrp3 in the development of cold stressinduced polycystic ovary phenotype in rats rfamiderelated peptide rfrp3 is a regulator of gnrh secretion from the brain but it can also act in human ovary to influence steroidogenesis we aimed to study the putative local role of rfrp3 in the ovary and its potential participation in the development of a polycystic ovary phenotype induced by chronic sympathetic stress cold stress we used adult spraguedawley rats divided into control and stressed groups in both groups we studied the effect of intraovarian exposure to rfrp3 on follicular development and plasma ovarian steroid concentrations we also tested the effect of rfrp3 on ovarian steroid production in vitro chronic in vivo intraovarian exposure to rfrp3 decreased basal testosterone concentrations and cold stressinduced progesterone production by the ovary in vitro rfrp3 decreased hcginduced ovarian progesterone and testosterone secretion immunohistochemistry and mrna expression analysis showed a decrease in rfrp and expression of its receptor in the ovary of stressed rats a result which is in line with the increased testosterone levels found in stressed rats in vivo application of rfrp3 recovered the low levels of secondary and healthy antral follicles found in stressed rats taken together our data indicate a previously unknown response of hypothalamic and ovarian rfrp3 to chronic cold stress influencing ovarian steroidogenesis and follicular dynamics thus it is likely that rfrp3 modulation in the ovary is a key component of development of the polycystic ovary phenotype