Nearly 10 years after the discovery that birds make a hormone1 that suppresses抑制,镇压 reproduction, University of California, Berkeley, neuroscientists神经系统科学家 have established that humans make it too, opening the door to development of a new class of contraceptive避孕用具 and possible treatments for cancer or other diseases. The hormone, gonadotropin促性腺激素 inhibitory hormone (GnIH), has the opposite effect from gonadotropin releasing hormone, a key reproductive hormone. While GnRH triggers a cascade喷流,层叠 of hormones4 that prime the body for sex and procreation, GnIH puts a brake on the cascade3.
"Identifying the inhibitory hormone in humans forces us to revise our understanding of the control mechanism5 of human reproduction," said first author Takayoshi Ubuka, a post-doctoral fellow in the UC Berkeley Department of Integrative Biology and in the Helen Wills Neuroscience Institute. "We hope this will stimulate6 clinical studies on people with precocious7 puberty性早熟 or in the area of contraception."
Because reproductive hormones often promote the growth of cancer cells, GnIH might also work as an anti-cancer agent.
"Frequently, treatment of hormone-responsive cancers involves GnRH antagonists敌手,对抗物 or very, very high doses of GnRH, which cause side effects," said George Bentley, UC Berkeley assistant professor of integrative综合的 biology. "Maybe we can use something that inhibits9 reproduction at physiological10 levels, so that we can bypass忽视,绕开 some of these side effects."
Ubuka, Bentley and their colleagues at UC Berkeley and in Japan and the United Kingdom report their findings in the Dec. 22 online issue of the public access journal PLoS ONE.
GnIH was discovered in 2000 in quail11 and has been studied in other birds, in mice and in sheep, but its role in humans has been hard to pin down阻止,确定. While the human genome contains the gene12 for GnIH, it was unclear if, when and where the protein hormone is produced, and whether it affects reproduction.
The UC Berkeley researchers extracted two versions of the hormone from human brains (five human hypothalami). They found that the human GnIH gene produces a precursor13 protein that is cut up to form 12 and 8 amino acid氨基酸 mature peptides多肽类,缩氨酸.
"One of the peptides in sheep has the same amino acid sequence氨基酸顺序 as the human peptide, so we can study its activity in sheep to learn about its activity in humans," Bentley said. "It's likely that the function of GnIH is evolutionarily conserved14."
They also showed that the hormones are present in a region of the brain, the hypothalamus下丘脑, that controls reproduction. In addition, GnIH affects nerve cells that secrete15 GnRH, which is in line with previous findings that GnIH down-regulates GnRH.
Finally, they found that the hypothalamus and pituitary脑垂体 – two key parts of the reproductive axis轴,轴心 in the brain have receptors for the hormones.
All the previous work on birds, rodents17, sheep and even macaque猕猴,恒河猴 monkeys – much of it performed by Bentley's group and by a group led by the discoverer of GnIH, Kazuyoshi Tsutsui at Waseda University in Tokyo hint at a wealth of interactions between GnIH and the reproductive system. Only recently, the human hormone was shown to inhibit2 the release of gonadotropin in sheep.
"GnIH pushes the pause button on reproduction, but in a variety of ways," Bentley said. "It can act on GnRH neurons in the hypothalamus, inhibiting18 GnRH release; it can act directly on pituitary; or it can influence the gonads生殖腺 directly. The overall effect is to inhibit reproduction, but at different levels of the reproductive axis16."
GnIH might even be a key regulator of puberty青春期,开花期, Ubuka said.
Bentley and Ubuka continue to investigate how GnIH acts in humans as well as in starlingsstarlings椋鸟 and zebra finches斑胸草雀.