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 5alpha-reductase isoform 1 mRNA expression.
Rzhevsky
D I
DI
Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia.
Zhokhov
S S
SS
Babichenko
I I
II
Goleva
A V
AV
Goncharenko
E N
EN
Baizhumanov
A A
AA
Murashev
A N
AN
Lipkin
V M
VM
Kostanyan
I A
IA
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D005837:Genitalia, Male / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism*; D009919:Orchiectomy; D009929:Organ Size; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D000728:Androgens; D009363:Neoplasm Proteins; D010455:Peptides; C091149:cell differentiation factor 8.2-kDa; D013739:Testosterone; D004958:Estradiol; D003345:Corticosterone