PMID- 24713504 OWN - NLM STAT- MEDLINE DCOM- 20141229 LR - 20220321 IS - 1878-5867 (Electronic) IS - 0039-128X (Linking) VI - 84 DP - 2014 Jun TI - Stimulation of androgen production by D-aspartate through the enhancement of StAR, P450scc and 3beta-HSD mRNA levels in vivo rat testis and in culture of immature rat Leydig cells. PG - 103-10 LID - S0039-128X(14)00070-1 [pii] LID - 10.1016/j.steroids.2014.03.016 [doi] AB - Previous studies have shown a role of d-aspartic acid (d-Asp) in testicular steroidogenesis. Here, we evaluated the effects of d-Asp on androgen production and on expression levels of mRNAs encoding specific steroidogenic key molecules. d-Asp was endogenously present in adult rat testis and its content paralleled to serum luteinizing hormone (LH) and, local and circulating androstenedione and testosterone levels. In vivod-Asp administration induced serum LH release, causing an indirect increase of androstenedione and testosterone levels by enhancing steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase/D5-D4 isomerases (3beta-HSD) mRNA levels. The direct endocrine role of d-Asp was evaluated using cultured immature Leydig cells (ILCs) obtained from 35days old rats. Cytoplasm and nucleus of ILCs localized d-Asp, while StAR marked the cytoplasm only. After 12h from d-Asp in vitro administration, ILCs resulted intensely d-Asp stained, and StaR protein level, evaluated by Western blotting, significantly increased. After 24h, significant androstenedione and testosterone syntheses were induced. At molecular level, d-Asp administration significantly increased StAR, P450scc and 3beta-HSD mRNAs at 2, 4 and 12h, respectively. The temporal shift on relative mRNA expression levels indicated that d-Asp exerted its physiological role through sequential gene cascade activation of those molecules implicated in the synthesis of androgens. Conclusively, our findings demonstrated that d-Asp is a local messenger in testis and give a contribution in understanding the complexity of local endocrine regulation as well as the molecular events leading the acquisition to a steroidogenic competence by ILCs. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Raucci, Franca AU - Raucci F AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Via Vivaldi 43, 81100 Caserta, Italy. Electronic address: francaraucci@hotmail.com. FAU - D'Aniello, Antimo AU - D'Aniello A AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Via Vivaldi 43, 81100 Caserta, Italy. FAU - Di Fiore, Maria Maddalena AU - Di Fiore MM AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Via Vivaldi 43, 81100 Caserta, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140405 PL - United States TA - Steroids JT - Steroids JID - 0404536 RN - 0 (Androgens) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 0 (steroidogenic acute regulatory protein) RN - 4SR0Q8YD1X (D-Aspartic Acid) RN - EC 1.1.- (3-Hydroxysteroid Dehydrogenases) RN - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme) SB - IM MH - 3-Hydroxysteroid Dehydrogenases/genetics/*metabolism MH - Androgens/*biosynthesis MH - Animals MH - Cholesterol Side-Chain Cleavage Enzyme/genetics/*metabolism MH - Chromatography, High Pressure Liquid MH - D-Aspartic Acid/*metabolism MH - Male MH - Phosphoproteins/genetics/*metabolism MH - RNA, Messenger/*genetics MH - Radioimmunoassay MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - Androstenedione OT - Steroidogenesis OT - Testis OT - Testosterone OT - d-Aspartic acid EDAT- 2014/04/10 06:00 MHDA- 2014/12/30 06:00 CRDT- 2014/04/10 06:00 PHST- 2013/09/10 00:00 [received] PHST- 2014/03/18 00:00 [revised] PHST- 2014/03/25 00:00 [accepted] PHST- 2014/04/10 06:00 [entrez] PHST- 2014/04/10 06:00 [pubmed] PHST- 2014/12/30 06:00 [medline] AID - S0039-128X(14)00070-1 [pii] AID - 10.1016/j.steroids.2014.03.016 [doi] PST - ppublish SO - Steroids. 2014 Jun;84:103-10. doi: 10.1016/j.steroids.2014.03.016. Epub 2014 Apr 5.