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

Abstract

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.

• Authors: D I Rzhevsky, S S Zhokhov, I I Babichenko, A V Goleva, E N Goncharenko, A A Baizhumanov, A N Murashev, V M Lipkin, I A Kostanyan
• Journal: Regulatory peptides (Regul Pept) Vol. 127 Issue 1-3 Pg. 111-21 (Apr 15 2005) ISSN: 0167-0115 [Print] Netherlands
• PMID: 15680477 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Neoplasm Proteins
• Peptides
• cell differentiation factor 8.2-kDa
• Testosterone
• Estradiol
• Corticosterone

Topics

• Androgens (metabolism)
• Animals
• Behavior, Animal (drug effects)
• Corticosterone (blood)
• Estradiol (blood)
• Genitalia, Male (cytology, metabolism)
• Humans
• Male
• Mice
• Mice, Inbred Strains
• Motor Activity (drug effects)
• Neoplasm Proteins (metabolism)
• Orchiectomy
• Organ Size
• Peptides (genetics, metabolism)
• Testosterone (blood)