期刊
BIOLOGY OF REPRODUCTION
卷 85, 期 5, 页码 987-995出版社
OXFORD UNIV PRESS INC
DOI: 10.1095/biolreprod.111.093492
关键词
diurnal; estradiol; estradiol receptor; feedback; GnRH receptor; gonadotropin-releasing hormone; ion channels
资金
- National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01 HD41469]
Estradiol has both negative and positive feedback actions upon gonadotropin-releasing hormone (GnRH) release; the latter actions trigger the preovulatory GnRH surge. Although neurobiological mechanisms of the transitions between feedback modes are becoming better understood, the roles of voltage-gated potassium currents, major contributors to neuronal excitability, are unknown. Estradiol alters two components of potassium currents in these cells: a transient current, I-A, and a sustained current, I-K. Kisspeptin is a potential mediator between estradiol and GnRH neurons and can act directly on GnRH neurons. We examined how estradiol, time of day, and kisspeptin interact to regulate these conductances in a mouse model exhibiting daily switches between estradiol negative (morning) and positive feedback (evening). Whole-cell voltage clamp recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice and from OVX mice treated with estradiol (OVX+E). There were no diurnal changes in either I-A or I-K in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX+E mice, I-A and I-K were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased I-A in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced I-A regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized I-A activation. These findings extend our understanding of both the neurobiological mechanisms of estradiol negative vs. positive regulation of GnRH neurons and of kisspeptin action on these cells.
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