Vasoactive intestinal peptide stimulates androgen biosynthesis by cultured neonatal testicular cells.
Vasoactive intestinal peptide (VIP) was originally isolated from porcine duodenum and considered to be a gut hormone. Recent evidence indicates that it may also be involved in reproductive functions. In this study, a possible action of VIP on steroidogenesis by cultured testicular cells was investigated. Neonatal testicular cells were treated in vitro with hormones for 3 days and medium steroid or cAMP content was measured by radioimmunoassay. Treatment of cultured cells with VIP (10(-9) to 10(-6) M) increased the production of testosterone, progesterone, and pregnenolone in a dose-dependent fashion. Testosterone production in response to 10(-6) M VIP was about 5-10% of that maximally induced by LH. Addition of methyl-isobutyl-xanthine, a phosphodiesterase inhibitor, to the VIP-containing cultures significantly enhanced production of testosterone by 13-fold, of progesterone by 9-fold, and of pregnenolone by 2.5-fold as compared to treatment with VIP alone. Additional experiments also showed a dose-dependent stimulation of cAMP production by VIP. The VIP-related hormones PHM-27, secretin, and glucagon also stimulated progesterone and testosterone production with a potency order (PHM-27 greater than secretin greater than glucagon) consistent with that observed for other VIP receptor-mediated actions. A direct stimulatory effect of VIP on Leydig cells was indicated in studies on steroidogenesis by testicular cells separated on a metrizamide density gradient. In these studies, VIP stimulated androgen production in an LH-responsive subpopulation of testis cells but failed to affect steroid production in non-LH-responsive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D005934:Glucagon / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D010451:Peptide PHI / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D010451:Peptide PHI; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D013739:Testosterone; D011374:Progesterone; D011284:Pregnenolone; D007986:Luteinizing Hormone; D005934:Glucagon; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D015056:1-Methyl-3-isobutylxanthine