Gonadotropin regulation and role of ovarian osteopontin in the periovulatory period

Abstract

Osteopontin (OPN), a secreted glycoprotein, has multiple physiological functions. This study investigated the regulation and roles of OPN in the mouse ovary during the periovulatory stages. Immature female mice were treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to simulate follicle maturation and ovulation. In situ hybridization and real-time RT-PCR were performed to assess expression of Opn in the periovulatory ovary. Granulosa cells (GCs) from PMSGprimed immature mice were cultured with or without hCG in the presence or absence of OPN, and effects on expression of Opn, progesterone synthesis, and vascular endothelial growth factor (VEGF) signaling were assessed by real-time RT-PCR, ELISA, and western blotting analysis. Opn transcripts were significantly upregulated 3 h after hCG treatment, followed by a peak at 16 h, and the transcripts localized to GCs. Incubation with hCG significantly increased quantities of Opn transcripts in GCs and OPN levels in the culture medium at 12 and 24 h. Furthermore, OPN treatment caused a significant increase in the levels of Star protein, P 450 cholesterol side-chain cleavage enzyme (p450scc), 3-betahydroxysteroid dehydrogenase (Hsd3b), and progesterone in the culture medium. OPN treatment promoted Vegf expression in GCs, which was significantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor. In addition, OPN treatment stimulated phosphorylation of AKT, a downstream PI3K signaling molecule. In conclusion, expression of Opn was upregulated in mouse ovarian GCs in response to a gonadotropin surge through epidermal growth factor receptor signaling, which enhances progesterone synthesis and Vegf expression during the early-luteal phase.

Polycystic ovary syndrome is associated with increased osteopontin levels

“…Adipose tissue dysfunction may also impact the pathophysiology of PCOS through its influence on metabolism and reproductive systems (6). In the present study, circulating OPN levels were significantly elevated in women with PCOS, and also overweight/obese women had significantly higher circulating OPN levels than lean (22) recently reported that OPN might be involved in the regulation of follicular growth and ovulation. They showed that OPN expression increased in mouse ovarian granulosa cells in response to gonadotropin.…”

“…They also observed that circulating OPN levels significantly increased following gonadotropin administration. They showed that OPN increases progesterone synthesis and expression of vascular endothelial growth factor (VEGF) in the early luteal phase (22). In addition, it has been previously demonstrated that circulating levels of certain adipokines show variations during the menstrual cycle (23,24).…”

Factors of angiogenesis in the development of physiological and pathological processes of the female gonads

“…Васкуляризация яичника в репродуктивном периоде онтогенеза регулируется и такими фак-торами, как остеопонтин, тромбоспондин-1, дельта-подобный лиганд 4, прокинетицин-1 и простагландин Е2 [11,21]. Все ýти факторы по-разному способствуют выживанию и функ-ционированию овариального резерва и профи-лактируют аномальный ангиогенез [11].…”

“…Ангиогенная активность находится под контро-лем основных ростовых факторов: сосудисто-ýн-дотелиального фактора роста, фактора роста фибробластов, ýпидермального фактора роста, фактора роста тромбоцитов, инсулино-подобно-го фактора роста-1, а также цитокинов (таких, как тумор-некротический фактор, интерлейки-ны, компоненты ýкстрацеллюлярного матрикса (ламинин, фибронектин) и их рецепторы (ин-тегрины), матричные металлопротеиназы и их тканевые ингибиторы и регуляторы, протеазы (плазминоген, активаторы урокиназы и уроки-назы тканевого типа), а также гипоксия, гипо-гликемия и стресс [1,8,10,18,19,20,21,22,23,24,25]. Следовательно, процессы ангиогенеза контролируются индукторами и ингибиторами васкуляризации [8,26,27].…”

Effect of Selinum on Ovarian Structure, Function and Serum Osteopontin Level in Rat Model of Polycystic Ovary Syndrome

“…Interestingly, Kuwabara et al, [10] reported that there is a link between OPN and ovarian function, as its expression in mouse ovaries and circulating levels were increased after gonadotropin administration.…”