HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice

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 5α-reductase isoform 1 mRNA expression. © 2004 Elsevier B.V. All rights reserved.

Rzhevsky D.I.1 , Zhokhov S.S.2 , Babichenko I.I. 3 , Goleva A.V. 3 , Goncharenko E.N.4 , Baizhumanov A.A.4 , Murashev A.N.1 , Lipkin V.M.1, 2 , Kostanyan I.A.2
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  • 1 Br. Shemyakin-Ovchinnikov Inst. B., Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russian Federation
  • 2 Shemyakin-Ovchinnikov Inst. B., Russian Academy of Sciences, 117997 Moscow, Russian Federation
  • 3 Department of Medicine, People's Friendship Univ. of Russia, 117198 Moscow, Russian Federation
  • 4 Biological Department, M.V. Lomonosov Moscow State Univ., 119992 Moscow, Russian Federation
5α-Reductase; Behavior; Brain; Dihydrotestosterone; Estradiol; Human leukemia differentiation factor; Peptide; Prostate; Seminal vesicles; Testosterone
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