Mechanisms of Hormone Action

Perturbation of Estradiol-Feedback Control of Luteinizing Hormone Secretion by Immunoneutralization Induces Development of Follicular Cysts in Cattle

Abstract

We used immunoneutralization of endogenous estradiol to investigate deficiencies in the estradiol-feedback regulation of LH secretion as a primary cause of follicular cysts in cattle. Twenty-one cows in the prostaglandin (PGF₂)-induced follicular phase were assigned to receive either 100 ml estradiol antiserum produced in a castrated male goat (n = 11, immunized group), or the same amount of castrated male goat serum (n= 10, control group). The time of injection of the sera was designated as 0 h and day 0. Five cows in each group were assigned to subgroups in which we determined the effects of estradiol immunization on LH secretion and follicular growth during the periovulatory period. The remaining 6 estradiol-immunized cows were subjected to long-term analyses of follicular growth and hormonal profiles, including evaluation of pulsatile secretion of LH. The remaining 5 control cows were used to determine pulsatile secretion of LH on day 0 (follicular phase) and day 14 (mid-luteal phase). The control cows exhibited a preovulatory LH surge within 48 h after injection of the control serum, followed by ovulation of the dominant follicle that had developed during the PGF₂-induced follicular phase. In contrast, the LH surge was not detected after treatment with estradiol antiserum. None of the 11 estradiol-immunized cows had ovulation of the dominant follicle, which had emerged before estradiol immunization and enlarged to over 20 mm in diameter by day 10. Long-term observation of the 6 immunized cows revealed that 5 had multiple follicular waves, with maximum follicular sizes of 20 to 45 mm at 10- to 30-day intervals, for over 50 days. The sixth cow experienced twin ovulations of the initial persistent follicles on day 18. The LH pulse frequency in the 5 immunized cows that showed the long-term turnover of cystic follicles ranged from 0.81 ± 0.13 to 0.97 ± 0.09 pulses/h during the experiment, significantly (p <0.05) higher than that in the mid-luteal phase of the control cows (0.23 ± 0.07). The mean LH concentration in the immunized cows was also generally higher than that in the luteal phase of control cows. However, the LH pulse and mean concentrations of LH after immunization were similar to those in the follicular phase of the control cows. Plasma concentrations of total inhibin increased (p <0.01) concomitant with the emergence of cystic follicles and remained high during the growth of cystic follicles, whereas FSH concentrations were inversely correlated with total inhibin concentrations. In conclusion, neutralization of endogenous estradiol resulted in suppression of the preovulatory LH surge but a normal range of basal LH secretion, and this circumstance led to an anovulatory situation similar to that with naturally occurring follicular cysts. These findings provide evidence that lack of LH surge owing to dysfunction in the positive-feedback regulation of LH secretion by estradiol can be the initial factor inducing formation of follicular cysts.