Rzhevsky D I, Zhokhov S S, Babichenko I I, Goleva A V, Goncharenko E N, Baizhumanov A A, Murashev A N, Lipkin V M, Kostanyan I A
Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia.
Regul Pept. 2005 Apr 15;127(1-3):111-21. doi: 10.1016/j.regpep.2004.11.005.
The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals. Male NMRI mice were castrated or sham-operated at the age of 55 days (after puberty). After that, HLDF-6 peptide was injected daily during 3 weeks, followed by behavioral, morphological and biochemical testing. HLDF-6 increased testosterone level (1.5- to 2-fold) both in sham-operated and castrated animals. Sexual activity and pain sensitivity, which are strongly reduced in castrates, were completely or partially recovered by HLDF-6. At the same time, the peptide caused some effects similar to castration in sham-operated animals: aggression and locomotor activity were decreased; oral grooming was prolonged. Morphological studies of accessory sex glands showed that HLDF-6 partially normalizes the morphology and functional activity of seminal vesicles in castrates, but it does not prevent castration-induced apoptosis of prostate epithelial cells. Based on these observations, we can assume that HLDF-6 peptide displays at least two effects on androgen hormones metabolism in males: it stimulates testosterone biosynthesis by both testes and adrenals and simultaneously inhibits its conversion to dihydrotestosterone (DHT), most probably by diminution of 5alpha-reductase isoform 1 mRNA expression.
六肽苏氨酸-甘氨酸-谷氨酸-天冬酰胺-组氨酸-精氨酸（HLDF-6）最初被鉴定为人白血病分化因子（HLDF）分子的活性片段，具有诱导分化、神经保护和抗药物滥用活性。其大多数体内效应仅在雄性动物身上得以揭示。我们研究了HLDF-6对各种生物体功能和行为反应的影响，这些功能和反应已知依赖雄激素类固醇激素，研究对象包括去势动物和正常（假手术）动物。雄性NMRI小鼠在55日龄（青春期后）时接受去势或假手术。之后，连续3周每天注射HLDF-6肽，随后进行行为、形态学和生化测试。HLDF-6使假手术动物和去势动物的睾酮水平均升高（1.5至2倍）。去势动物中大幅降低的性活动和疼痛敏感性通过HLDF-6得以完全或部分恢复。同时，该肽在假手术动物中产生了一些类似于去势的效应：攻击性和运动活性降低；口腔梳理时间延长。附属性腺的形态学研究表明，HLDF-6使去势动物精囊的形态和功能活性部分恢复正常，但它并不能阻止去势诱导的前列腺上皮细胞凋亡。基于这些观察结果，我们可以推测HLDF-6肽对雄性雄激素激素代谢至少有两种作用：它刺激睾丸和肾上腺的睾酮生物合成，同时抑制其转化为二氢睾酮（DHT），最有可能是通过减少5α-还原酶同工型1 mRNA的表达来实现的。
