Separate negative feedback effects of estrogen on the pituitary and the central nervous system in the ovariectomized rhesus monkey.

The site(s) of the negative feedback action of estrogen on gonadotropin secretion were studied in the ovariectomized rhesus monkey by observing the serum LH and FSH responses to intravenous GnRH injections at various times after implantation of Silastic capsules filled with estrogen. Circulating estrogen concentrations produced by the capsules were within the normal midcycle range for this species. Four h after estrogen implantation, no LH or FSH response was seen to the GnRH injection, indicating a suppressive effect of the steroid directly on the pituitary. Twelve and 22 h after estrogen implantation, however, the LH and FSH responses were equal to or larger than control responses. Since preinjection LH and FSH levels were below control values at these times and the pituitary responded to exogenous GnRH, it appears that endogenous GnRH secretion was affected, indicating an inhibitory action of estrogen on the central nervous system. Thus these experiments suggest 2 separate negative feedback actions of estrogen: a transient one directly on the pituitary and a longer lasting effect on the central nervous system.