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. Key words: Caspase-3 activity, Corpus luteum, Growth hormone (GH), Insulin-like growth factor-I (IGF-I), Pig, Progesterone (J. Reprod. Dev. 51: [727][728][729][730][731][732][733] 2005) eptin mediates transmission of information about nutritional status to centers that control the function of the reproductive system. The porcine leptin receptor complementary DNA has be en clo ned and se que nce d, an d th e gen e expression evaluated in the porcine ovary [1]. The authors of the related report showed the presence of leptin mRNA in porcine corpus luteum, theca, and granulosa cells. In a recent paper [2], a biphasic effect was shown for leptin. The authors of the report measured progesterone (P4) production by cultured porcine granulosa cells isolated from ovaries of prepubertal gilts and showed that leptin at 10 ng/ml increased P4 production, while a dose of 1000 ng/ml decreased it. In vivo serum leptin concentrations rise during the follicular phase and reach their peak during the luteal phase of the spontaneous cycle [3]. We previously showed a direct, maturation-dependent