In 1957, Béla Flerkó and János Szentágothai implanted ovarian and liver tissue autografts into two distinct hypothalamic regions or the adenohypophysis of female rats. The tiny pieces of liver were absorbed. By contrast, the ovary implants survived and continued to release oestrogens. Furthermore, when the ovarian tissue was implanted below the hypothalamic paraventricular nucleus, the weight of the uterus decreased and the oestrous cycle of most animals was arrested in dioestrus. Both of these consequences were attributed to reduced peripheral oestrogen signalling and were absent in rats that had the ovarian implants in either the mammillary region or the adenohypophysis. Flerkó and Szentágothai interpreted their results as evidence that the oestrogen released from the ovarian grafts, which could not inhibit gonadotrophic activity via direct effects on the adenohypophysis, acted on the nervous tissue of the hypothalamus to inhibit secretion of follicle-stimulating hormone.

The basic conclusion of the authors that oestrogens act predominantly in the hypothalamus to inhibit the secretion of gonadotrophs has remained valid since 1957. However, it should be recognized that the lesion and implantation techniques available at that time did not allow these investigators to precisely determine the hypothalamic site where negative feedback takes place. The results of these lesion experiments directed their attention to the anterior hypothalamus.

1957 年，Béla Flerkó 和 János Szentágothai 将自体卵巢和肝脏组织移植到雌性大鼠的两个不同的下丘脑区域或腺垂体中。肝脏的小碎片被吸收了。相比之下，卵巢植入物存活下来并继续释放雌激素。此外，当卵巢组织植入下丘脑室旁核下方时，子宫重量下降，大多数动物的发情周期在间情期停止。这两种后果都是由于外周雌激素信号减少所致，而在乳头区域或腺垂体植入卵巢的大鼠中则不存在。Flerkó 和 Szentágothai 将他们的结果解释为证据，即卵巢移植物释放的雌激素不能通过直接作用于腺垂体来抑制促性腺激素活性，而是作用于下丘脑的神经组织，抑制促卵泡激素的分泌。

作者的基本结论是，雌激素主要作用于下丘脑，抑制促性腺激素的分泌，这一结论自 1957 年以来一直有效。然而，应该认识到，当时可用的病变和植入技术不允许这些研究人员精确确定发生负反馈的下丘脑部位。这些损伤实验的结果将他们的注意力引向了下丘脑前部。