The Expression of a Mitochondria-Localized Glutamic Acid-Rich Protein (MGARP/OSAP) Is Under the Regulation of the HPG Axis

Abstract

The hypothalamic-pituitary-gonadal (HPG) axis exerts a profound effect on animal development, reproduction, and response to stress, and new insights into its complicated functional activities are continuously being made. In the present study, by using immunohistochemical studies and different mouse models (ovariectomy and ob/ob mice), we systemically analyzed the expression of a novel mitochondria-localized glutamic acid-rich protein (MGARP)/ovary-specific acid protein and demonstrated that MGARP is under the regulation of the HPG axis. MGARP is highly enriched in steroidogenic tissues and the visual system. Interestingly, its expression increases as mice develop. Early in development, MGARP is mainly detected in the retina and adrenal gland. At this early developmental stage, its expression is not detectable in the gonads, but its expression in the gonads dramatically increases during the first 2-4 wk after birth. Importantly, MGARP levels correlate with estrogen levels in the ovaries during the estrous cycle, and estrogen regulates the expression of MGARP in a tissue-specific manner and through a feedback regulatory mechanism. Functional inhibition of GnRH with an antagonist strongly reduces MGARP levels, and knockout of leptin (ob/ob) significantly reduces the MGARP expression in follicular granular cells. We proposed a model that elucidates the role MGARP plays in the HPG axis. Within the HPG axis loop, MGARP participates in hormone biosynthesis while being under the regulation of the hormones derived from the HPG axis.

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.…”

Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP‐1c Signaling Pathway in ApoE−/− Mice Fed with a High‐Fat Diet

“…The adipose tissue from the other three groups of mice were removed and stored at −80°C to examine the protein expressions of Insig-1, SCAP, and SREBP-1c. The protocol for western blotting was previously described by us [17]. Primary antibodies including Insig-1 (Abcam, ab70784, 1 : 200), SREBP-1c (Abcam, ab28481, 1 : 1000), SCAP (Abcam, ab19013, 1 : 1000), IRS-1 (Abcam, ab52167, 1 : 1000), PI3K (Abcam, ab151549, 1 : 1000), Akt (Abcam, ab8805, 1 : 500), mTORC1(Abcam, ab2732, 1 : 200), PAQR3 (Abcam, ab174327, 1 : 250), and β -actin (Beijing Zhongshan Golden Bridge Biotechnology Co., TA-09, 1 : 1000) were used in this study.…”

A genomic atlas of human adrenal and gonad development

“…These genes include MGARP (also known as OSAP ), which may be involved in mitochondrial trafficking, MAP3K15 ( ASK3 ) involved in cell signalling of stress, and the imprinted gene DLK1 ( PREF1 ) implicated in growth and differentiation (Guasti et al, 2013; Naguro et al, 2012; Zhou et al, 2011). Two genes that have not been studied previously are GRAMD1B and RMDN2 ( FAM82A1 ).…”

“…MGARP has been implicated in mitochondrial trafficking and steroidogenesis (Jia et al, 2014; Jin et al, 2012; Zhou et al, 2011), but may also be a key target of OCT4 during reprogramming to pluripotency (Tiemann et al, 2014). DLK1 is an imprinted gene that is involved in inhibiting adipocyte differentiation, which has previously been shown to be expressed in the outer undifferentiated zone of the male rat adrenal gland and signals to the adrenal capsule to regulate zonation (Guasti et al, 2013).…”