Yaron Zvi, Gur Gal, Melamed Philippa, Rosenfeld Hanna, Elizur Abigail, Levavi-Sivan Berta
Department of Zoology, Tel-Aviv University, Tel Aviv 69978, Israel.
Int Rev Cytol. 2003;225:131-85. doi: 10.1016/s0074-7696(05)25004-0.
Neurohormones similar to those of mammals are carried in fish by hypothalamic nerve fibers to regulate directly follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Gonadotropin-releasing hormone (GnRH) stimulates the secretion of FSH and LH and the expression of the glycoprotein hormone alpha (GPalpha), FSHbeta, and LHbeta, as well as their secretion. Its signal transduction leading to LH release is similar to that in mammals although the involvement of cyclic AMP-protein kinase A (cAMP-PKA) cannot be ruled out. Dopamine (DA) acting through DA D2 type receptors may inhibit LH release, but not that of FSH, at sites distal to activation of protein kinase C (PKC) and PKA. GnRH increases the steady-state levels of GPalpha, LHbeta, and FSHbeta mRNAs. Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and neuropeptide Y (NPY) potentiate GnRH effect on gonadotropic cells, and also act directly on the pituitary cells. Whereas PACAP increases all three subunit mRNAs, NPY has no effect on that of FSHbeta. The effect of these peptides on the expression of the gonadotropin subunit genes is transduced differentially; GnRH regulates GPalpha and LHbeta via PKC-ERK and PKA-ERK cascades, while affecting the FSHbeta transcript through a PKA-dependent but ERK-independent cascade. The signals of both NPY and PACAP are transduced via PKC and PKA, each converging at the ERK level. NPY regulates only GPalpha- and LHbeta-subunit genes whereas PACAP regulates the FSHbeta subunit as well. Like those of the mammalian counterparts, the coho salmon LHbeta gene promoter is driven by a strong proximal tripartite element to which three different transcription factors bind. These include Sf-1 and Pitx-1 as in mammals, but the function of the Egr-1 appears to have been replaced by the estrogen receptor (ER). The GnRH responsive region in tilapia FSHbeta 5' flanking region spans the canonical AP1 and CRE motifs implicating both elements in conferring GnRH responsiveness. Generally, high levels of gonadal steroids are associated with high LHbeta transcript levels whereas those of FSHbeta are reduced when pituitary cells are exposed to high steroid levels. Gonadal or hypophyseal activin also participate in the regulation of FSHbeta and LHbeta mRNA levels. However, gonadal effects are dependent on the gender and stage of maturity of the fish.
与哺乳动物类似的神经激素由鱼类下丘脑神经纤维携带，直接调节促卵泡激素（FSH）和促黄体生成素（LH）。促性腺激素释放激素（GnRH）刺激FSH和LH的分泌以及糖蛋白激素α（GPα）、FSHβ和LHβ的表达及其分泌。其导致LH释放的信号转导与哺乳动物相似，尽管不能排除环磷酸腺苷 - 蛋白激酶A（cAMP - PKA）的参与。通过多巴胺D2型受体起作用的多巴胺（DA）可能在蛋白激酶C（PKC）和PKA激活位点的远端抑制LH释放，但不抑制FSH释放。GnRH增加GPα、LHβ和FSHβ mRNA的稳态水平。垂体腺苷酸环化酶激活多肽（PACAP）38和神经肽Y（NPY）增强GnRH对促性腺细胞的作用，并且也直接作用于垂体细胞。虽然PACAP增加所有三个亚基的mRNA，但NPY对FSHβ的mRNA没有影响。这些肽对促性腺激素亚基基因表达的影响以不同方式转导；GnRH通过PKC - ERK和PKA - ERK级联调节GPα和LHβ，同时通过PKA依赖但ERK独立的级联影响FSHβ转录本。NPY和PACAP的信号均通过PKC和PKA转导，各自在ERK水平汇聚。NPY仅调节GPα和LHβ亚基基因，而PACAP也调节FSHβ亚基。与哺乳动物对应物一样，银大麻哈鱼LHβ基因启动子由一个强大的近端三联体元件驱动，三种不同的转录因子与之结合。这些包括与哺乳动物中一样的Sf - 1和Pitx - 1，但Egr - 1的功能似乎已被雌激素受体（ER）取代。罗非鱼FSHβ 5'侧翼区域中的GnRH反应区域跨越典型的AP1和CRE基序，表明这两个元件都赋予GnRH反应性。一般来说，高水平的性腺类固醇与高LHβ转录水平相关，而当垂体细胞暴露于高类固醇水平时，FSHβ的转录水平降低。性腺或垂体激活素也参与FSHβ和LHβ mRNA水平的调节。然而，性腺的影响取决于鱼的性别和成熟阶段。
