PMID- 23332974 OWN - NLM STAT- MEDLINE DCOM- 20130628 LR - 20131121 IS - 1556-5653 (Electronic) IS - 0015-0282 (Linking) VI - 99 IP - 5 DP - 2013 Apr TI - Different levels of leptin regulate different target enzymes involved in progesterone synthesis. PG - 1460-6 LID - S0015-0282(12)02523-X [pii] LID - 10.1016/j.fertnstert.2012.12.014 [doi] AB - OBJECTIVE: To study the effects of different doses of leptin on the expression of proteins involved in P synthesis, such as steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (P450scc), and 3beta-hydroxysteroid dehydrogenase (3betaHSD). DESIGN: Experimental studies. SETTING: Research laboratory. ANIMAL(S): Immature rats primed with gonadotropins to induce ovulation. INTERVENTION(S): In vivo studies: rats received either an acute or daily treatment with leptin. In vitro studies: ovarian explants were cultured in the absence or presence of leptin (0.3-500 ng/mL). MAIN OUTCOME MEASURE(S): The expression of both messenger RNA and protein of StAR, P450scc, and 3betaHSD were measured by reverse transcription-polymerase chain reaction (PCR) and Western blot, respectively. RESULT(S): The acute treatment with leptin, which inhibits the ovulatory process, caused a significant reduction in the ovarian expression of P450scc without changes in StAR or 3betaHSD. In contrast, the daily treatment, which induces the ovulatory process, showed an increased expression of the ovarian 3betaHSD protein, without differences in the other proteins measured. We also found that leptin increased the protein of both P450scc and 3betaHSD at physiological levels and inhibited both messenger RNA and protein of 3betaHSD at higher concentrations. CONCLUSION(S): The results indicate that 1) leptin is able to regulate the expression of the 3betaHSD protein in a dose-dependent manner; and 2) leptin seems to exert its dual effects on P synthesis on different targets in a dose-dependent manner. CI - Copyright (c) 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Bilbao, Maria Guillermina AU - Bilbao MG AD - Centro de Estudios Farmacologicos y Botanicos (CEFYBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. FAU - Di Yorio, Maria Paula AU - Di Yorio MP FAU - Faletti, Alicia Graciela AU - Faletti AG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130116 PL - United States TA - Fertil Steril JT - Fertility and sterility JID - 0372772 RN - 0 (Gonadotropins) RN - 0 (Leptin) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 0 (steroidogenic acute regulatory protein) RN - 4G7DS2Q64Y (Progesterone) 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 - Age Factors MH - Animals MH - Cholesterol Side-Chain Cleavage Enzyme/*genetics/metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Gene Expression Regulation, Enzymologic/drug effects/physiology MH - Gonadotropins/pharmacology MH - Leptin/pharmacology/*physiology MH - Ovulation/drug effects/physiology MH - Ovulation Induction/methods MH - Phosphoproteins/*genetics/metabolism MH - Progesterone/*biosynthesis MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley EDAT- 2013/01/22 06:00 MHDA- 2013/07/03 06:00 CRDT- 2013/01/22 06:00 PHST- 2012/08/27 00:00 [received] PHST- 2012/11/29 00:00 [revised] PHST- 2012/12/10 00:00 [accepted] PHST- 2013/01/22 06:00 [entrez] PHST- 2013/01/22 06:00 [pubmed] PHST- 2013/07/03 06:00 [medline] AID - S0015-0282(12)02523-X [pii] AID - 10.1016/j.fertnstert.2012.12.014 [doi] PST - ppublish SO - Fertil Steril. 2013 Apr;99(5):1460-6. doi: 10.1016/j.fertnstert.2012.12.014. Epub 2013 Jan 16.