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 a...

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Published in:	Regulatory peptides Vol. 127; no. 1; pp. 111 - 121
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier B.V 15-04-2005 Amsterdam Elsevier
Subjects:	5α-Reductase Androgens - metabolism Animals Behavior Behavior, Animal - drug effects Brain Corticosterone - blood Dihydrotestosterone Estradiol Estradiol - blood Genitalia, Male - cytology Genitalia, Male - metabolism Human leukemia differentiation factor Humans Male Mice Mice, Inbred Strains Motor Activity - drug effects Neoplasm Proteins - metabolism Orchiectomy Organ Size Peptide Peptides - genetics Peptides - metabolism Prostate Seminal vesicles Testosterone Testosterone - blood Testosterone Brain Dihydrotestosterone Seminal vesicles 5α-Reductase Human leukemia differentiation factor Behavior Peptide Estradiol Prostate
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-0115 1873-1686
DOI:	10.1016/j.regpep.2004.11.005