A 5-day estradiol therapy, in amounts reproducing concentrations of the early-mid follicular phase, prevents the activation of the hypothalamo-pituitary-adrenal axis by interleukin-1 alpha in the ovariectomized rhesus monkey.

Abstract

In a previous report, we have shown that intracerebroventricular (icv) administration of the cytokine interleukin-1 alpha (IL-1 alpha) in the ovariectomized (OVX) rhesus monkey results in the acute activation of the hypothalamo-pituitary-adrenal (HPA) axis and the inhibition of LH and FSH secretion. Here, we compare the cortisol response to IL-1 alpha administration in OVX monkeys and in OVX animals replaced with estradiol (E) to reproduce E concentrations typical of the early-mid follicular phase. Cortisol, LH and FSH were measured after an icv infusion of physiological saline or IL-1 alpha (2.1 or 4.2 micrograms/30 min) in both groups. E-containing capsules were implanted sc 5 days prior to the experiment. In OVX, E concentrations were < 5 pg/ml. Cortisol concentrations decreased throughout the afternoon after saline infusion (to 49.7 +/- 5.1% of baseline at 5 h; n = 7), but increased significantly after IL-1 alpha to 158.3 +/- 13.8% (n = 7). In OVXE, cortisol also declined after saline (to 76.4 +/- 16.2%; n = 5). There were 2 types of response to IL-1 alpha: in grp 1 (mean E: 18.0 +/- 0.7 pg/ml), the cortisol response was similar to that in OVX (160.8 +/- 17.0%; n = 5), while in grp 2 (E: 30.7 +/- 3.1 pg/ml), the cortisol response was absent (66.6 +/- 7.2% of baseline at 5 h; NS vs saline in OVXE; n = 7). The cortisol response to IL-1 alpha was restored in 2 monkeys when E was increased to > 100 pg/ml, confirming our previous observations.(ABSTRACT TRUNCATED AT 250 WORDS)