Direct effects of luteal regression on anterior pituitary response to GNRH

The preovulatory period of the ewe is marked by a dramatic decrease in concentrations of progesterone in serum during the late luteal phase, followed by elevated luteinizing hormone (LH) secretion, final follicular maturation and ovulation. This experiment was designed to ascertain the extent to which removal of endogenous progesterone negative feedback at the anterior pituitary gland, independent of effects at the hypothalamus, promotes increased secretion of LH in the hours immediately after induction of luteolysis. Estrus was synchronized in ovary-intact ewes with two injections of prostaglandin F2 alpha (PGF2 alpha) analog given 10 d apart (Day 0 = second day after the second PGF2 alpha injection). Ewes were subjected to hypothalamic-pituitary disconnection (HPD; n = 6) on Day 3 and were pulsed with gonadotropin-releasing hormone (GnRH). Ewes were used during the estrous cycle or received approximately 400 IU pregnant mare serum gonadotropin (PMSG) on Day 2 to stimulate ovulation; there was no difference (P < 0.10) in ovulation rate or progesterone production between these two groups. Luteal regression was induced by injection of PGF2 alpha analog on approximately Day 10 of the estrous cycle. Blood samples were collected around exogenous GnRH pulses before and at 2- or 4-hr intervals after PGF2 alpha administration and concentrations of LH and progesterone determined. At 4, 12, and 24 hr after PGF2 alpha administration, mean serum progesterone levels in all ewes had decreased by 54.7%, 66.2% and 89.4%, respectively (P < 0.05) from pre-injection levels. The decrease in progesterone was associated with an increase (P < 0.01) in LH pulse amplitude with means at 4-hr post-PGF2 alpha ranging from 190% to 288% of pre PGF2 alpha values. Mean serum LH levels were also increased (P < 0.01) within 4 hr of PGF2 alpha administration and remained elevated at all but the 24-hr time point. The timing of this increase (within 4 hr) indicates that it is independent of changes in serum estradiol concentrations, which do not increase for at least 16 hr after induction of luteolysis. Thus, removal of endogenous progesterone negative feedback at the anterior pituitary gland in the hours immediately after induction of luteolysis seems to play a role in facilitating LH release independently of hypothalamic action.