REGULATION OF STEROID-PRODUCTION AND ITS FUNCTION WITHIN THE CORPUS-LUTEUM

During the second half of the luteal phase, the human corpus luteum be comes responsive to regular luteinizing hormone (LH) pulses. These LH pulses stimulate progesterone secretion tonically, and during this ton ic stimulation, additional LH-independent progesterone pulses occur, w hich are particularly pronounced in women with human chorionic gonadot ropin-stimulated luteal function. No progesterone pulses are seen in w omen suffering from corpus luteum deficiency due to absent LH pulses. The corpus luteum thus has a progesterone pulse generator turned on bq ; gonadotropins but functioning for several hours without further gona dotropic support. This pulse generator appears to be regulated by intr aluteal auto-/paracrine mechanisms, which we have investigated in a po rcine model using molecular, cellular, and in vivo tools. Luteal oxyto cin and progesterone release occurs in tightly coupled pulses. In vivo , oxytocin and prostaglandin F-2 alpha(PGF(2 alpha)) stimulate estradi ol and progesterone release and estradiol itself further stimulates pr ogesterone release. Analysis of the different luteal cell compartments (large luteal cells, small luteal cells, fibroblasts) suggests an int raluteal circuit that involves paracrine effects of estradiol, oxytoci n, and PGF(2 alpha). At the time of luteolysis, the luteotropic effect s of estradiol are inhibited by tumor necrosis factor derived from inv ading macrophages and the intraluteal circuit is thereby disrupted, le ading to luteolysis. (C) 1998 by Elsevier Science Inc.