The negative feedback action of progesterone on luteinizing hormone release is not associated with changes in GnRH...

Progesterone is the ovarian hormone that times events in the ovine reproductive cycle. When elevated, this ovarian hormone acts centrally to inhibit both the tonic and surge modes of gonadotrophin releasing hormone (GnRH) release. Two studies were performed to address the underlying neural mechanisms. The first tested the hypothesis that the rapid rise in GnRH release, that results from an acute fall in progesterone concentrations (such as occurs following luteolysis), is temporally associated with a rapid rise in the cellular content of GnRH mRNA. Three groups of ovariectomised (OVX) ewes were treated with exogenous progesterone for 10 days, while one remained steroid free (OVX, n=7). To determine the effects of acute progesterone (P) withdrawal, ewes were killed on day 10 while implants were still in place (OVX+P, n=6) or 4 (OVX-P4, n=7) or 12 h (OVX-P12, n=7) after progesterone removal. Coronal sections through the rostral portion of the medial preoptic area (rPOA) were processed for cellular in-situ hybridization for GnRH mRNA. An increase in progesterone concentrations markedly suppressed luteinizing hormone (LH) release, while removal of the implants caused progesterone concentrations to fall (P<0.01) within 1 h and LH pulse frequency to increase (P<0.05) within 4 h. Despite these progesterone-induced changes in LH/GnRH release there were no differences in the cellular content of GnRH mRNA among the four groups. In the second study, three groups of ovariectomised ewes were used to determined whether the inhibitory actions of early (EL; n=8) and mid-luteal (ML; n=8) phase concentrations of progesterone on LH release are accompanied by a decrease in GnRH mRNA expression. P inhibited the secretion of LH in a dose dependant manner; pulses of LH were virtually absent in the ML group. Despite this marked inhibitory steroid action, there was no significant difference in the cellular content of GnRH mRNA among the OVX, OVX (EL) and OVX (ML) groups. Thus, both the negative feedback actions of physiological concentrations of progesterone on GnRH release and the rapid escape from progesterone-inhibition are independent of changes in the cellular content of GnRH mRNA. These data suggest that the mechanism by which progesterone controls the timing of events in the ovine oestrous cycle is primarily by altering the secretion of GnRH rather than GnRH biosynthesis.