Testosterone increases TRH biosynthesis in epididymis but not heart of zinc-deficient rats.
Enzymes responsible for the posttranslational processing of precursor proteins to form alpha-amidated peptide hormones require the availability of several cofactors, including zinc, copper, and ascorbic acid. For this reason, we studied the effects of 6 weeks of a zinc-deficient diet (ZD1; 1 microgram zinc per g diet), pair-feeding (PF), and marginal zinc deficiency (ZD6; 6 micrograms zinc per g diet) compared to a control diet (36 micrograms/g zinc) on the conversion of prepro-TRH to TRH in epididymides, testes, prostate, pancreas, and heart of young adult, male Sprague-Dawley rats. In the epididymis, severe zinc deficiency (ZD1 diet) reduced TRH and TRH-like peptides to undetectable levels. In ZD6 animals, TRH was selectively inhibited 80%, while pair-feeding increased all of these peptide levels compared to controls. A similar effect of zinc deficiency on the TRH precursor peptides was observed. A quantitative loss of TRH from the testes of ZD1 was also observed. Zinc deficiency results in a substantial reduction in body weight and testosterone production in male rats. Exogenous testosterone (T) supplementation of ZD1 rats resulted in a selective increase in the TRH concentration of the epididymis but not of the heart. The change in steady-state levels of TRH precursor peptides in the hearts of the ZD1+T rats was consistent with a reduction in the activity of the zinc-dependent carboxypeptidase H enzyme. We conclude that severe zinc deficiency inhibits TRH biosynthesis in reproductive tissues of the male rat due to the combined effects of hypogonadism and inhibition of the zinc-dependent carboxypeptidase H.
Pekary
A E
AE
Endocrinology Research Laboratory, Veterans Administration Wadsworth Medical Center, Los Angeles, CA 90073.
Lukaski
H C
HC
Mena
I
I
Smith
S M
SM
Bhasin
S
S
Hershman
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000172:deficiency / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000737:chemistry; D014018:Tissue Distribution; D015032:Zinc / Q000172:deficiency*
D013739:Testosterone; D013973:Thyrotropin-Releasing Hormone; C040476:thyrotropin-releasing hormone, Gly; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D015032:Zinc; D011761:Pyrrolidonecarboxylic Acid