Progesterone treatment that either blocks or augments the estradiol-induced gonadotropin-releasing hormone surge is associated with different patterns of hypothalamic neural activation

Progesterone can either augment or inhibit the surge of gonadotropin-releas ing hormone (GnRH) that drives the preovulatory luteinizing hormone (LH) su rge. This study investigated the central mechanisms through which progester one might achieve these divergent effects by examining the effects of exoge nous steroids on the activation of GnRH neurons and non-GnRH-immunopositive cells in the preoptic area/anterior hypothalamus of steroid-treated ovarie ctomized ewes. Fos expression tan index of cellular activation) was examine d during the estradiol-induced GnRH surge in ewes treated with progesterone using regimes that have been reported to either augment (progesterone pret reatment) or inhibit (progesterone treatment at the time of the surge-induc ing estradiol increment) the GnRH surge. Control groups received either no progesterone pretreatment or no surge-inducing estradiol increment. Inducti on of an LH surge was associated with a significant (p < 0.0001) increase i n the proportion of activated GnRH neurons, irrespective of whether ewes re ceived progesterone pretreatment. However, the number of non-GnRH-immunopos itive cells activated during the surge was significantly (p < 0.0001) incre ased in ewes that received the progesterone pretreatment. By contrast, the proportion of GnRH neurons and non-GnRH-immunopositive cells that expressed Fos was significantly (p < 0.0001) reduced in ewes in which the surge was inhibited by progesterone compared to ewes in which a surge was stimulated. These data indicate that(l) progesterone pretreatment increases the activa tion of non-GnRH cells during the estradiol-induced surge, but does not aff ect the proportion of GnRH neurons activated and (2) when administered conc urrently with a surge-inducing estradiol increment, progesterone prevents t he activation of GnRH neurons and non-GnRH cells that is normally associate d with the estradiol-induced surge. Therefore, progesterone does not appear to augment the GnRH surge by increasing the proportion of GnRH neurons tha t are activated by estradiol, whereas inhibition of the GnRH surge involves prevention of the activation of GnRH neurons. Thus, the augmentation and i nhibition of the GnRH surge by progesterone appear to be regulated via diff erent effects on the GnRH neurosecretory system. Copyright (C) 2001 S. Karg er AG, Basel.