Within developing ovarian follicles, oocyte maturation requires coordinated interplay between multiple specialized cells: the oocyte, granulosa cells (GCs), and enveloping stromal (mainly theca externa interna that provide essential structural steroidogenic support, respectively). Although numerous studies have focused on explaining interactions occur within its surrounding GCs throughout matur...

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 ...

The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP and officially designated NR5A1) has emerged as an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of the cytochrome P450 steroid hydroxylases, SF-1 has considerably broader roles, as evidenced from studies in knockout mice lacking SF-1. The ...

The signaling phosphatidylinositol lipids PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3) bind nuclear receptor 5A family (NR5As), but their regulatory mechanisms remain unknown. Here, the crystal structures of human NR5A1 (steroidogenic factor-1, SF-1) ligand binding domain (LBD) bound to PIP2 and PIP3 show the lipid hydrophobic tails sequestered in the hormone pocket, as predicted. However, unlike cl...

Orphan nuclear receptors such as germ cell nuclear factor (GCNF), steroidogenic factor 1 (SF-1) and liver receptor homolog-1 (LRH-1), are emerging as important ovarian factors in regulating female reproduction. Within the ovary, GCNF (NR6A1) expression is restricted to the oocyte, while SF-1 (NR5A1) is expressed only in the somatic cells, such as granulosa, thecal and luteal cells, and intersti...

PURPOSE OF REVIEW This review focuses on the pathogenesis, diagnosis, management and long-term outcomes of disorders of sex development, specifically women with Swyer syndrome (46,XY complete gonadal dysgenesis). RECENT FINDINGS Recent discoveries have broadened our understanding of the complex pathways involved in normal and abnormal sex development. In 46,XY gonadal dysgenesis, lack of test...

Next generation sequencing (NGS), using massive parallel sequencing, is increasingly being used in the clinical setting. It is a high throughput technique that offers a fast and cost-effective testing solution for genetic disorders with a number of candidate genes. In this study we have employed NGS to sequence 48 samples that had been referred to the Molecular Genetics Department for the inves...

The nuclear receptor LRH-1 (NR5A2) functions to regulate expression of a number of genes associated with bile acid homeostasis and other liver functions, but mechanisms that modulate its activity remain unclear. We have found that mitogenic stimuli, including treatment with phorbol myristate (PMA), increase LRH-1 transactivation. This response maps to the hinge and ligand binding domains of LRH...