Researchers at the Institute of Hydrobiology, Chinese Academy of Sciences, discovered that GnRH3 neuropeptide controls primordial germ cell proliferation and sex differentiation in zebrafish. Using gene-edited mutants, they found reduced PGC numbers and more males in adults. The findings appear in…
Gonadotropin-releasing hormone, or GnRH, also called luteinizing hormone-releasing hormone or LHRH, acts as a neurohormone from the hypothalamus. It helps control reproduction in vertebrates. Scientists first isolated GnRH from pig and sheep brains in 1971. The GnRH family includes at least 28 types, with 15 from vertebrates and 13 from invertebrates.
The hypothalamus releases GnRH in pulses to manage the reproductive axis. This triggers the pituitary to release gonadotropins, luteinizing hormone or LH, and follicle-stimulating hormone or FSH, into the bloodstream periodically. Those hormones prompt the gonads to produce estradiol, progesterone, inhibin, and testosterone, all key to reproduction.
GnRH serves as a central element in the hypothalamic-pituitary-gonad axis of vertebrates. It influences gonad development, maturation, and reproduction. Researchers at the Institute of Hydrobiology, Chinese Academy of Sciences, used zebrafish to uncover a novel role for the GnRH3 neuropeptide and its mechanism.
Hu Wei, a researcher at the Institute of Hydrology, created a zebrafish model with GnRH3 mutation through gene editing technology. In these GnRH3 knockout fish, partial male development occurred, and the share of adult males rose notably. The study marks the first identification of GnRH3's role in primordial germ cell or PGC proliferation and sex differentiation during early zebrafish embryo stages.
In early embryos before the sphere stage, PGC numbers in GnRH3 mutants matched wild-type fish. Later developmental stages showed far fewer PGCs in mutants compared to wild type. Proliferation and migration analysis indicated normal migration for PGCs post-GnRH3 mutation, but proliferation dropped significantly.
Further work showed GnRH3 governs PGC proliferation in early zebrafish embryos via MAPK signaling pathways. It also controls expression of genes linked to female and male gonadal cells during the key early sex differentiation window. These actions influence overall sex differentiation in zebrafish.
The results appeared online recently in Endocrinology. The full reference lists authors Ke Feng, Xuefan Cui, Yanlong Song, Binbin Tao, Ji Chen, Jing Wang, Shaojun Liu, Yonghua Sun, Zuoyan Zhu, Vance L Trudeau, and Wei Hu from 2019: "Gnrh3 regulates PGC proliferation and sex differentiation in developing zebrafish." Endocrinology.
GnRH agonists and antagonists represent synthetic versions of the GnRH peptide hormone. They reduce LH and FSH release from the anterior pituitary mediated by GnRH, leading to castrate levels of testosterone. GnRH antagonists block the GnRH receptor directly.
GnRH agonists disrupt the normal pulsatile signaling of natural GnRH. Constant high activity from agonists downregulates GnRH receptors, lowering LH, FSH, and testosterone. Agonists typically cause an early rise in LH, FSH, and testosterone before downregulation sets in. Antagonists avoid this androgen surge.
Peptides referenced: Gonadorelin.
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