Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis.
The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide have long been considered as putative regulators of testicular functions. In vitro evidence suggests that VIP could play an important role in testosterone biosynthesis. However, the endogenous role of VIP on testicular functions remained to be demonstrated. In C57BL/6 mice exhibiting a complete disruption of the VIP gene, we first observed here that serum testosterone levels were lower than those of WT littermates. At the age of 4 months, this phenotype was accompanied with a reduction of expression of StAR and 3-beta-hydroxysteroid dehydrogenase (3beta-HSD) in the testis. In addition, serum levels of FSH but not LH were reduced in young knock-out (KO) males. Testicular anatomy also revealed a higher percentage of degenerated seminiferous tubules in the 4-month-old VIP KO animals when compared with WT. In 15-month-old animals, control males showed typical testicular aging, including a severe degeneration of seminiferous tubules, a dramatic decrease in serum levels of testosterone, and a reduction in StAR and 3beta-HSD gene expression. In age-matching VIP KO males, the levels of serum testosterone and steroidogenic enzymes were still very low. Interestingly, in contrast to that observed in young mice, testicular degeneration at 15 months was significantly less severe in VIP KO than WT mice. All together, these results suggest that 1) VIP is an important factor for regulating testosterone biosynthesis and FSH secretion and 2) VIP may influence testicular aging.
Lacombe
Arnaud
A
Department of Human Genetics, David Geffen School of Medicine at UCLA, Gonda Center, University of California, Room 6357, 695 Charles Young Drive South, Los Angeles, California 90095-7088, USA.
Lelievre
Vincent
V
Roselli
Charles E
CE
Muller
Jean-Marc
JM
Waschek
James A
JA
Vilain
Eric
E
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D013739:Testosterone / Q000032:analysis* / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000235:genetics*; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D014660:Vasoactive Intestinal Peptide; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015096:3-Hydroxysteroid Dehydrogenases