Oakley Amy E, Breen Kellie M, Clarke Iain J, Karsch Fred J, Wagenmaker Elizabeth R, Tilbrook Alan J
Department of Molecular and Integrative Physiology, University of Michigan, 1301 East Catherine Street, Room 7744 Med Sci II 0622, Ann Arbor, Michigan 48109-0404, USA.
Endocrinology. 2009 Jan;150(1):341-9. doi: 10.1210/en.2008-0587. Epub 2008 Sep 18.
Stress-like elevations in plasma glucocorticoids suppress gonadotropin secretion and can disrupt ovarian cyclicity. In sheep, cortisol acts at the pituitary to reduce responsiveness to GnRH but does not affect GnRH pulse frequency in the absence of ovarian hormones. However, in ewes during the follicular phase of the estrous cycle, cortisol reduces LH pulse frequency. To test the hypothesis that cortisol reduces GnRH pulse frequency in the presence of ovarian steroids, the effect of cortisol on GnRH secretion was monitored directly in pituitary portal blood of follicular phase sheep in the presence and absence of a cortisol treatment that elevated plasma cortisol to a level observed during stress. An acute (6 h) cortisol increase in the midfollicular phase did not lower GnRH pulse frequency. However, a more prolonged (27 h) increase in cortisol beginning just before the decrease in progesterone reduced GnRH pulse frequency by 45% and delayed the preovulatory LH surge by 10 h. To determine whether the gonadal steroid milieu of the follicular phase enables cortisol to reduce GnRH pulse frequency, GnRH was monitored in ovariectomized ewes treated with estradiol and progesterone to create an artificial follicular phase. A sustained increment in plasma cortisol reduced GnRH pulse frequency by 70% in this artificial follicular phase, in contrast to the lack of an effect in untreated ovariectomized ewes as seen previously. Thus, a sustained stress-like level of cortisol suppresses GnRH pulse frequency in follicular phase ewes, and this appears to be dependent upon the presence of ovarian steroids.
血浆糖皮质激素类似应激的升高会抑制促性腺激素的分泌,并可能扰乱卵巢周期性。在绵羊中,皮质醇作用于垂体以降低对促性腺激素释放激素(GnRH)的反应性,但在没有卵巢激素的情况下不影响GnRH脉冲频率。然而,在发情周期卵泡期的母羊中,皮质醇会降低促黄体生成素(LH)脉冲频率。为了验证皮质醇在存在卵巢类固醇的情况下会降低GnRH脉冲频率这一假设,在有或没有使血浆皮质醇升高至应激时观察到水平的皮质醇处理的情况下,直接监测皮质醇对卵泡期绵羊垂体门脉血中GnRH分泌的影响。卵泡中期急性(6小时)皮质醇升高并未降低GnRH脉冲频率。然而,在孕酮下降前开始的更长时间(27小时)的皮质醇升高使GnRH脉冲频率降低了45%,并使排卵前LH峰延迟了10小时。为了确定卵泡期的性腺类固醇环境是否使皮质醇能够降低GnRH脉冲频率,在用雌二醇和孕酮处理以创建人工卵泡期的去卵巢母羊中监测GnRH。与之前在未处理的去卵巢母羊中未观察到影响相反,在这个人工卵泡期血浆皮质醇的持续升高使GnRH脉冲频率降低了70%。因此,持续的类似应激水平的皮质醇会抑制卵泡期母羊的GnRH脉冲频率,这似乎依赖于卵巢类固醇的存在。