Ovarian Regulation of Pulsatile Luteinizing Hormone Secretion During Late Gestation in the Rat

The object of this study was to examine the influence of both estradiol (E2) and progesterone (P) alone or in combination on luteinizing hormone (LH) pulse amplitude and frequency during the interval between Days 21 and 22 of gestation. This was done by analyzing pulsatile LH release in rats bled on Days 21 and 22 of gestation, and in animals ovariectomized (OVX) on Day 21, implanted with silastic capsules producing plasma levels of E2 and/or P characteristic of the Day 21 to 22 interval, and bled on Day 22 Pulsatile LH release increased between Days 21 and 22 due to an increase in pulse frequency and a small elevation in pulse amplitude. OVX produced no further increase in pulse frequency but markedly enhanced the small change in pulse amplitude. Preventing either the decline in plasma P that normally occurs between Days 21 and 22, or just the small additional decrease in plasma P levels produced by OVX, had no suppressive effect on pulse amplitude or frequency, although Day 22 levels of P alone augmented the normal increase in pulse frequency occurring between Days 21 and 22. Restoration of physiological plasma E2 levels had no effect on the normal increase in pulse frequency, but partially attenuated the OVX-induced increase in pulse amplitude. Replacement of physiological Day 22 levels of both E2 and P also decreased LH pulse amplitude, although amplitude was not significantly different from that seen following E2 replacement alone, and was still greater than the normal Day 22 value. In contrast, restoration of physiological plasma levels of E2+ P caused a suppression of LH pulse frequency below that normally seen on Day 22. While E2+ P did not completely prevent the OVX-induced increase in pulse amplitude, administration of charcoal-extracted porcine follicular fluid to rats OVX on Day 21, and in which physiological plasma levels of E2+ P were restored, caused a further reduction in pulse amplitude. These data demonstrate that 1) marked increases in LH pulse amplitude are prevented from occurring between Days 21 and 22 of gestation by ovarian steroids, notably E2, and that this suppression is enhanced by a non-steroidal factor present in porcine follicular fluid, 2) neither E2 or P alone suppresses LH pulse frequency on Day 22 of gestation; LH pulse frequency increases on Day 22 because the plasma level of one of these steroids, P, markedly declines, and 3) restoration of physiological plasma levels of both steroids in the absence of the ovary produces an unphysiological suppression of pulse frequency, i.e. results in a lower pulse frequency than normally occurs in the presence of these same plasma steroid levels in animals with their ovaries intact. One hypothesis consistent with the latter observation is that at the end of gestation in the rat the ovary may produce a factor which ‘protects’ the frequency of the LH pulse generator from the negative feedback action of ovarian steroids. This allows an increase in LH pulse frequency and mean blood LH levels, and thereby facilitates ovarian follicular development and the normal progress of the first postpartum estrous cycle.