[Significance and mechanism of desensitization to the gonadotropin-inhibiting effect of estrogen. 1. Studies on prepubertal desensitization].

In immature female rats, both a distinctive diminution of the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically implanted estradiol and a simultaneous rise of the estrogen and gonadotrophin levels in the blood were revealed during the last days preceding the onset of puberty. Based on these findings, studies on the neurohormonal mechanism underlying this prepubertal desensitization to the negative estrogen feedback were performed. Bilateral lesioning of the medial preoptic area (MPOA) which induced precocious puberty also diminished significantly the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically administered estrogen. Similar responses were recorded following the implantation of very low quantities of estrogen into the MPOA, whereas medial preoptic implants of the antiestrogen clomiphene citrate impaired the spontaneous prepubertal desensitization and delayed the onset of puberty. It is concluded from the results that the prepubertal increase of the estrogen concentration in the blood itself induces the desensitization to estrogen by an inhibitory effect on medial preoptic neurons. Preliminary clinical and experimental findings suggest that a comparable mechanism may be operative in humans, too.