Progesterone treatment that either blocks or augments the estradiol-induced gonadotropin-releasing hormone surge is associated with different patterns of hypothalamic neural activation
Ta. Richter et al., Progesterone treatment that either blocks or augments the estradiol-induced gonadotropin-releasing hormone surge is associated with different patterns of hypothalamic neural activation, NEUROENDOCR, 73(6), 2001, pp. 378-386
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.