In Vitro Effect of Leptin on Growth Hormone (GH)- and Insulin-Like Growth Factor-I (IGF-I)-stimulated Progesterone Secretion and Apoptosis in Developing and Mature Corpora Lutea of Pig Ovaries

Abstract

This study was designed to determine whether leptin modulates growth hormone (GH)- and insulin like growth factor-I (IGF-I)-stimulated progesterone (P4) production by corpora lutea (CL). Luteal cells were recovered from early developing (ELP) and mature (MLP) corpora lutea and cultured in defined medium with various combinations of GH, IGF-I, and leptin (0-200 ng/ml). P4 concentrations in the media were determined after 48 h of culture. During the early luteal phase, leptin at all used doses had no effect on basal P4 secretion, but it did suppress caspase-3 activity. When added in combination with GH, it had no effect on either GH-stimulated P4 secretion or apoptosis. Concomitant treatment with IGF-I and leptin decreased P4 secretion and parallelly increased the apoptosis rate. In mature corpora lutea of full secreting capacity, leptin at all doses had no effect on basal and GH-stimulated P4 secretion and caspase-3 activity. Only at the highest dose (200 ng/ml) when leptin was added with IGF-I did P4 secretion decrease with no effect on the caspase-3 activity. We conclude that the role of leptin is to restrict the stage of CL formation. During this luteal phase, leptin acts as an antiapoptotic factor and, at the same time, reverses antiapoptotic action of IGF-I, thereby protecting cells from excessive apoptosis and supporting retention of appropriate cell numbers, which is necessary for maintenance of homeostasis in developing CL.