Testosterone selectively influences protein kinase-C-coupled secretion of proluteinizing hormone-releasing hormone-derived peptides.
LHRH and GnRH-associated peptide (GAP) are two major pro-LHRH-derived peptides which are secreted from median eminence (ME) nerve terminals in vitro. The purpose of the present experiment was to determine whether manipulation of gonadal steroid levels in vivo influenced selectively the in vitro secretion of LHRH and GAP under basal or K+ and phorbol ester (PDBu) stimulation. Secretion of both peptides under each of these three conditions was reduced at least 2-fold in 2-week orchidectomized (ORDX) rats relative to the level in intact controls. Tissue stores of LHRH and GAP were also depressed in the ME of ORDX relative to control rats. When the data were expressed in terms of the percentage of peptide secreted per ME, both groups secreted similar percentages of the peptides into the medium under basal and K+-stimulated conditions. Interestingly, PDBu-activated secretion of LHRH and GAP remained depressed in ORDX animals. The nerve terminals from ORDX animals were not susceptible to a more rapid depletion of releasable peptides, since both groups secreted similar percentages of the peptides during repeated K+ depolarization. By comparison, protein kinase C (PKC)-coupled secretion from ORDX rats was selectively affected, since secretion of pro-LHRH-derived peptides became even more depressed with successive activation with PDBu. Immediate replacement with testosterone after ORDX fully restored the peptide levels in tissue and the LHRH and GAP secretory response to PKC activation. Since testosterone influenced both tissue stores and PDBu-stimulated secretion of LHRH and GAP, this steroid may selectively regulate biosynthesis and secretion of pro-LHRH-derived peptides through activation of the metabolic cascade involving the PKC system.
Wetsel
W C
WC
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Negro-Vilar
A
A
D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D009919:Orchiectomy; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology*
D011498:Protein Precursors; C050502:gonadotropin releasing hormone associated peptide; D007987:Gonadotropin-Releasing Hormone; D015240:Phorbol 12,13-Dibutyrate; D013739:Testosterone; D011493:Protein Kinase C; D011188:Potassium