Bertram Richard, Li Yue-Xian
Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4510, USA.
Bull Math Biol. 2008 Nov;70(8):2211-28. doi: 10.1007/s11538-008-9341-2. Epub 2008 Aug 9.
The timed secretion of the luteinizing hormone (LH) and follicle stimulating hormone (FSH) from pituitary gonadotrophs during the estrous cycle is crucial for normal reproductive functioning. The release of LH and FSH is stimulated by gonadotropin releasing hormone (GnRH) secreted by hypothalamic GnRH neurons. It is controlled by the frequency of the GnRH signal that varies during the estrous cycle. Curiously, the secretion of LH and FSH is differentially regulated by the frequency of GnRH pulses. LH secretion increases as the frequency increases within a physiological range, and FSH secretion shows a biphasic response, with a peak at a lower frequency. There is considerable experimental evidence that one key factor in these differential responses is the autocrine/paracrine actions of the pituitary polypeptides activin and follistatin. Based on these data, we develop a mathematical model that incorporates the dynamics of these polypeptides. We show that a model that incorporates the actions of activin and follistatin is sufficient to generate the differential responses of LH and FSH secretion to changes in the frequency of GnRH pulses. In addition, it shows that the actions of these polypeptides, along with the ovarian polypeptide inhibin and the estrogen-mediated variations in the frequency of GnRH pulses, are sufficient to account for the time courses of LH and FSH plasma levels during the rat estrous cycle. That is, a single peak of LH on the afternoon of proestrus and a double peak of FSH on proestrus and early estrus. We also use the model to identify which regulation pathways are indispensable for the differential regulation of LH and FSH and their time courses during the estrous cycle. We conclude that the actions of activin, inhibin, and follistatin are consistent with LH/FSH secretion patterns, and likely complement other factors in the production of the characteristic secretion patterns in female rats.
在发情周期中，垂体促性腺细胞定时分泌促黄体生成素（LH）和促卵泡生成素（FSH）对于正常生殖功能至关重要。LH和FSH的释放受下丘脑GnRH神经元分泌的促性腺激素释放激素（GnRH）刺激。它由发情周期中变化的GnRH信号频率控制。奇怪的是，LH和FSH的分泌受GnRH脉冲频率的差异调节。在生理范围内，随着频率增加，LH分泌增加，而FSH分泌呈现双相反应，在较低频率时达到峰值。有大量实验证据表明，这些差异反应的一个关键因素是垂体多肽激活素和卵泡抑素的自分泌/旁分泌作用。基于这些数据，我们开发了一个纳入这些多肽动力学的数学模型。我们表明，一个纳入激活素和卵泡抑素作用的模型足以产生LH和FSH分泌对GnRH脉冲频率变化的差异反应。此外，它表明这些多肽的作用，连同卵巢多肽抑制素以及雌激素介导的GnRH脉冲频率变化，足以解释大鼠发情周期中LH和FSH血浆水平的时间进程。也就是说，在发情前期下午出现LH的单峰，在发情前期和发情早期出现FSH的双峰。我们还使用该模型来确定哪些调节途径对于发情周期中LH和FSH的差异调节及其时间进程是不可或缺的。我们得出结论，激活素、抑制素和卵泡抑素的作用与LH/FSH分泌模式一致，并且可能在雌性大鼠特征性分泌模式的产生中补充其他因素。
