生殖轴由出生在原始鼻子中的促性腺激素释放激素(GnRH)神经元网络控制,该网络与嗅觉系统的轴突一起迁移到下丘脑。先天性嗅觉缺失(无法嗅觉)通常与人类GnRH缺乏症有关的观察结果导致了普遍的观点,即GnRH神经元依赖于嗅觉结构到达大脑。但这一假设尚未得到证实。
这项工作的目的是确定在内部和外部嗅觉结构完全缺失的情况下正常生殖功能的潜力。
我们对11例先天性紫荆患者进行了全面的表型研究。通过对另外40名国际患者的医疗记录和研究问卷的审查,这些研究得到了加强。
所有男性患者均表现出GnRH缺乏的临床和/或生化体征,和5名男性研究的人没有黄体生成素(LH)脉冲,提示GnRH活性缺失。亲自研究的6名女性也有不成熟的LH资料,然而,3名女性有自发性乳房发育,2名女性(从远处研究)有正常的乳房发育和月经周期,暗示一个完整的生殖轴。向2名GnRH缺乏症患者服用搏动性GnRH显示垂体反应正常,但男性患者性腺衰竭。
紫荆患者告诉我们GnRH神经元,生殖轴的关键看门人,与正常迁移和功能的嗅觉结构相关,但可能不依赖于嗅觉结构,更广泛地说,说明极端人类表型在回答有关人类胚胎学的基本问题方面的力量。
The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed.
The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures.
We conducted comprehensive phenotyping studies in 11 patients with congenital
arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients.
All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient.
Patients with
arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.