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

The 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.