Regulation of steroid production and its function within the corpus luteum.

During the second half of the luteal phase, the human corpus luteum becomes responsive to regular luteinizing hormone (LH) pulses. These LH pulses stimulate progesterone secretion tonically, and during this tonic stimulation, additional LH-independent progesterone pulses occur, which are particularly pronounced in women with human chorionic gonadotropin-stimulated luteal function. No progesterone pulses are seen in women suffering from corpus luteum deficiency due to absent LH pulses. The corpus luteum thus has a progesterone pulse generator turned on by gonadotropins but functioning for several hours without further gonadotropic support. This pulse generator appears to be regulated by intraluteal auto-/paracrine mechanisms, which we have investigated in a porcine model using molecular, cellular, and in vivo tools. Luteal oxytocin and progesterone release occurs in tightly coupled pulses. In vivo, oxytocin and prostaglandin F2 alpha(PGF2 alpha) stimulate estradiol and progesterone release and estradiol itself further stimulates progesterone release. Analysis of the different luteal cell compartments (large luteal cells, small luteal cells, fibroblasts) suggests an intraluteal circuit that involves paracrine effects of estradiol, oxytocin, and PGF2 alpha. At the time of luteolysis, the luteotropic effects of estradiol are inhibited by tumor necrosis factor derived from invading macrophages and the intraluteal circuit is thereby disrupted, leading to luteolysis.