Different levels of leptin regulate different target enzymes involved in progesterone synthesis.

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 3ß-hydroxysteroid dehydrogenase (3ßHSD). 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 3ßHSD 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 3ßHSD. In contrast, the daily treatment, which induces the ovulatory process, showed an increased expression of the ovarian 3ßHSD protein, without differences in the other proteins measured. We also found that leptin increased the protein of both P450scc and 3ßHSD at physiological levels and inhibited both messenger RNA and protein of 3ßHSD at higher concentrations. CONCLUSION(S): The results indicate that 1) leptin is able to regulate the expression of the 3ßHSD 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.