Department of Biology, East Carolina University, Greenville, NC 27858, USA.
Department of Chemistry, East Carolina University, Greenville, NC 27858, USA.
Gen Comp Endocrinol. 2019 Oct 1;282:113218. doi: 10.1016/j.ygcen.2019.113218. Epub 2019 Jul 10.
Progestin receptor membrane component (Pgrmc1 & 2) is a heme-binding protein. Studies on Pgrmc1 have suggested possible roles in heme binding, activation of steroid-synthesizing P450s, along with binding and transferring of membrane proteins. However, the studies of Pgrmc1's paralog, Pgrmc2 are still lacking. In order to determine the physiologic function(s) of Pgrmc2, we generated a zebrafish mutant line (pgrmc2). We found a reduction in both spawning frequency and the number of embryos produced in female pgrmc2. This subfertility is caused by reduced oocyte maturation (germinal vesicle breakdown, GVBD) in pgrmc2 in vivo. Nonetheless, oocytes from pgrmc2 had similar sensitivity to 17α,20β-dihydroxy-4-pregnen-3-one (DHP, a maturation induced progestin in zebrafish) compared with wildtype (wt) in vitro. Therefore, we hypothesized that oocyte maturation tardiness found in vivo, could be due to lack of progestin in pgrmc2. Interestingly, we found significant reduced expression of hormones, receptors, and steroid synthesizing enzymes including lhcgr, egfra, ar, and esr2, cyp11a1 and hsd3b1. In addition, DHP levels in pgrmc2 ovaries showed a significant decrease compared to those in wt. In summary, we have provided a plausible molecular mechanism for the physiological functions of Pgrmc2 in the regulation of female fertility, likely via regulation of receptors and steroids in the ovary, which in turn regulates oocyte maturation in zebrafish.
孕激素受体膜成分（Pgrmc1 和 2）是一种血红素结合蛋白。对 Pgrmc1 的研究表明，它可能在血红素结合、激活类固醇合成 P450 以及膜蛋白的结合和转移中发挥作用。然而，对 Pgrmc1 同源物 Pgrmc2 的研究仍然缺乏。为了确定 Pgrmc2 的生理功能，我们生成了一个斑马鱼突变系（pgrmc2）。我们发现雌性 pgrmc2 的产卵频率和胚胎数量都减少了。这种生育力低下是由于体内 pgrmc2 的卵母细胞成熟（卵母细胞核破裂，GVBD）减少所致。尽管如此，与野生型（wt）相比，pgrmc2 的卵母细胞对 17α,20β-二羟基-4-孕烯-3-酮（DHP，一种在斑马鱼中诱导成熟的孕激素）的敏感性相似。因此，我们假设体内发现的卵母细胞成熟迟缓可能是由于 pgrmc2 缺乏孕激素。有趣的是，我们发现包括 lhcgr、egfra、ar 和 esr2、cyp11a1 和 hsd3b1 在内的激素、受体和类固醇合成酶的表达显著降低。此外，与 wt 相比，pgrmc2 卵巢中的 DHP 水平显著降低。总之，我们为 Pgrmc2 在调节雌性生育力方面的生理功能提供了一个合理的分子机制，可能是通过调节卵巢中的受体和类固醇，进而调节斑马鱼的卵母细胞成熟。
