Expression of Ovary-Specific Acidic Protein in Steroidogenic Tissues: A Possible Role in Steroidogenesis

Abstract

Ovary-specific acidic protein (OSAP) is a novel molecule discovered from a genomic project designed to identify ovary-selective genes in mice. Whereas public databases suggest extraovarian expression of OSAP, its tissue distribution has not yet been well documented. Thus, the expression profile of mouse and human OSAP was determined by quantitative real-time RT-PCR using RNAs isolated from various tissues. The results demonstrate that the human and mouse OSAP expression profiles are similar; OSAP is prominently expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Placenta served as an exception and possessed minimal level of OSAP mRNA. Immunohistochemical studies show that mouse OSAP localizes almost exclusively to the steroid-producing cells of the ovary, adrenal gland, and testis. Consistent with predictions made by several subcellular localization algorithms, dual labeling studies in Y-1 mouse adrenocortical cells indicate OSAP resides in the mitochondria. Because of its abundant expression in steroidogenic cells and mitochondrial localization, a role for OSAP in steroidogenesis was determined. OSAP silencing by specific small interfering RNAs significantly inhibits 8-bromoadenosine-cAMP-induced progesterone production in Y-1 cells. Reduction in OSAP levels results in mitochondrial fragmentation and a decrease in the cellular content of mitochondrial DNA, indicative of decreased mitochondrial abundance. Lastly, 8-bromoadenosine-cAMP does not regulate OSAP protein expression in Y-1 cells as is the case for other steroidogenic components known to be induced by cAMP. Collectively these results suggest that OSAP is involved in steroidogenesis, potentially through its ability to maintain mitochondrial abundance and morphology.

snoRNA U17 Regulates Cellular Cholesterol Trafficking

“…The reciprocal relationship between U17 snoRNA and HUMMR mRNA abundance in the developing mouse ovary suggests that the U17 snoRNA-HUMMR pathway may play a role in regulating steroid hormone production and postnatal gonadal maturation. Enrichment of HUMMR in steroidogenic tissues and its regulation under hypothalamic-pituitary-gonadal axis is consistent with such a role (Matsumoto et al, 2009; Zhou et al, 2011). Our findings that the developmental decline in U17 snoRNA expression is concomitant with the de-repression of HUMMR expression and the steroidogenic demand, and that in vivo knockdown of U17 snoRNA increases HUMMR expression and steroid synthesis, implicates U17 snoRNA as an upstream regulator that modulates mitochondrial cholesterol import.…”

“…HUMMR is highly expressed in steroidogenic tissues and is regulated by the hypothalamic-pituitary-gonadal axis in mice (Matsumoto et al, 2009; Zhou et al, 2011). Since cholesterol is an obligate precursor for mitochondrial steroid synthesis, we examined the U17 snoRNA-HUMMR pathway in steroidogenic tissues.…”

Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease

“…Hypoxia-up-regulated mitochondrial movement regulator (HUMMR) was termed corneal endothelium-specific protein-1 in corneal endothelium, potentially maintaining mitochondrial abundance and morphology [10]. It has recently been demonstrated that HUMMR, expressed in neurons, astrocytes and even whole brain, is closely associated with mitochondrial movement and mainly regulates mitochondrial distribution and transport [11].…”

Mitochondria-Localized Glutamic Acid-Rich Protein (MGARP) Gene Transcription Is Regulated by Sp1

“…Our previous studies have demonstrated that MGARP is highly expressed in the inner segment of the photoreceptor (IS), outer plexiform layer (OPL) and ganglion cell layer (GCL) of the retina, which are enriched with mitochondria [3]. Additional studies have indicated that MGARP is involved in steroidogenesis through its ability to maintain mitochondrial abundance and morphology, and importantly, it is also highly expressed in the organs involved in steroidogenesis, such as the ovary, testis, adrenal gland and brain [4], [5]. MGARP can also be induced by HIF-1 and hypoxia, biasing mitochondrial transport in the anterograde direction and joining the mitochondrial dance [6], [7].…”