The role of the orphan receptor SF–1 in the development and function of the ovary

SUMMARYThe development of oocyte and ovulation require a precise synchronization at systemic and local levels. Nuclear receptors are involved in the regulation of these processes. In addition to the well–known nuclear receptors (e.g. receptors for estradiol, progesterone, glucocorticoids), a group of “orphan receptors” are distinguished within a receptor family. The orphan receptors are characterized by a lack of defined physiological ligands. Steroidogenic Factor 1 (SF–1, NR5A1) is a member of the orphan receptor group and is involved in the regulation of reproductive processes. The SF–1 structure is similar to that of the steroid receptors but does not have a modulatory domain. The SF–1 as a transcription factor may interact with genes in three main ways: a/by a mechanism typical for nuclear receptors, encompassing homodimerization of SF–1 units, b/by a formation heterodimers with other nuclear receptors, and c/by action as a monomer. During fetal development, the SF–1, is responsible for differentiation of the gonads and, during the postnatal period, it is responsible for the increase in the expression of genes involved in steroidogenesis. Knock–out of SF–1 gene leads to a rapid death of newly born mice with symptoms of severe adrenal insufficiency. In humans, SF–1 dysfunction causes an adrenal insufficiency and infertility. Learning of the SF–1 and other orphan receptors’ action mechanisms, will allow the creation of specific drugs, helpful in preventing some diseases of the female reproductive tract.