PMID- 28596078 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20181202 IS - 1095-6840 (Electronic) IS - 0016-6480 (Linking) VI - 250 DP - 2017 Sep 1 TI - Identification of an oxytocinase/vasopressinase-like leucyl-cystinyl aminopeptidase (LNPEP) in teleost fish and evidence for hypothalamic mRNA expression linked to behavioral social status. PG - 58-69 LID - S0016-6480(17)30209-5 [pii] LID - 10.1016/j.ygcen.2017.06.002 [doi] AB - The vasotocin/vasopressin and isotocin/mesotocin/oxytocin family of nonapeptides regulate social behaviors and physiological functions associated with reproductive physiology and osmotic balance. While experimental and correlative studies provide evidence for these nonapeptides as modulators of behavior across all classes of vertebrates, mechanisms for nonapeptide inactivation in regulating these functions have been largely overlooked. Leucyl-cystinyl aminopeptidase (LNPEP) - also known as vasopressinase, oxytocinase, placental leucine aminopeptidase (P-LAP), and insulin-regulated aminopeptidase (IRAP) - is a membrane-bound zinc-dependent metalloexopeptidase enzyme that inactivates vasopressin, oxytocin, and select other cyclic polypeptides. In humans, LNPEP plays a key role in the clearance of oxytocin during pregnancy. However, the evolutionary diversity, expression distribution, and functional roles of LNPEP remain unresolved for other vertebrates. Here, we isolated and sequenced a full-length cDNA encoding a LNPEP-like polypeptide of 1033 amino acids from the ovarian tissue of Amargosa pupfish, Cyprinodon nevadensis. This deduced polypeptide exhibited high amino acid identity to human LNPEP both in the protein's active domain that includes the peptide binding site and zinc cofactor binding motif (53.1% identity), and in an intracellular region that distinguishes LNPEP from other aminopeptidases (70.3% identity). Transcripts encoding this LNPEP enzyme (lnpep) were detected at highest relative abundance in the gonads, hypothalamus, forebrain, optic tectum, gill and skeletal muscle of adult pupfish. Further evaluation of lnpep transcript abundance in the brain of sexually-mature pupfish revealed that lnpep mRNAs were elevated in the hypothalamus of socially subordinate females and males, and at lower abundance in the telencephalon of socially dominant males compared to dominant females. These findings provide evidence of an association between behavioral social status and hypothalamic lnpep transcript abundance and suggest that variation in the rate of VT/IT peptide inactivation by LNPEP may be a contributing component in the mechanism whereby nonapeptides regulate social behavior. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Elkins, Emma A AU - Elkins EA AD - Biological Sciences Department, Center for Coastal Marine Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USA. FAU - Walti, Kayla A AU - Walti KA AD - Biological Sciences Department, Center for Coastal Marine Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USA. FAU - Newberry, Kathryn E AU - Newberry KE AD - Biological Sciences Department, Center for Coastal Marine Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USA. FAU - Lema, Sean C AU - Lema SC AD - Biological Sciences Department, Center for Coastal Marine Sciences, California Polytechnic State University, San Luis Obispo, CA 93407, USA. Electronic address: slema@calpoly.edu. LA - eng PT - Journal Article DEP - 20170606 PL - United States TA - Gen Comp Endocrinol JT - General and comparative endocrinology JID - 0370735 RN - 0 (DNA, Complementary) RN - 0 (RNA, Messenger) RN - EC 3.4.11.3 (Cystinyl Aminopeptidase) RN - EC 3.4.11.3 (leucyl-cystinyl aminopeptidase) SB - IM MH - Adult MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - *Behavior, Animal MH - Cystinyl Aminopeptidase/chemistry/*metabolism MH - DNA, Complementary/genetics MH - Female MH - Fishes/*genetics/*metabolism MH - Gene Expression Profiling MH - Humans MH - Hypothalamus/*metabolism MH - Male MH - Phylogeny MH - Pregnancy MH - Principal Component Analysis MH - Prosencephalon/metabolism MH - RNA, Messenger/genetics/metabolism MH - *Social Behavior OTO - NOTNLM OT - Aggression OT - Aminopeptidase OT - Behavior OT - Fish OT - Isotocin OT - Oxytocin OT - Vasopressin OT - Vasotocin EDAT- 2017/06/10 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/06/10 06:00 PHST- 2017/03/17 00:00 [received] PHST- 2017/06/03 00:00 [revised] PHST- 2017/06/04 00:00 [accepted] PHST- 2017/06/10 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/06/10 06:00 [entrez] AID - S0016-6480(17)30209-5 [pii] AID - 10.1016/j.ygcen.2017.06.002 [doi] PST - ppublish SO - Gen Comp Endocrinol. 2017 Sep 1;250:58-69. doi: 10.1016/j.ygcen.2017.06.002. Epub 2017 Jun 6.