Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta

Abstract

This study was designed to test the hypothesis that basal estrone conjugate (E1C) profiles do not accurately detect ovarian function when ovarian estrogen production is low or absent. We employed surgical removal of active ovaries from laboratory rhesus macaques to simulate an acute decline in ovarian estrogen production. In the first experiment, urine samples collected prior to and following ovariectomy (Ovx) were subjected to high-performance liquid chromatography (HPLC) separation. Eluates were then assayed for E1C immunoreactive components. The results indicated a modest decrease in total immunoreactive polar conjugates following ovariectomy, with no substantial change in the overall retention profile. In the second experiment, estradiol (E2) cypionate injections were used to replace the E2 component of ovarian estrogen production in the treated (Tx) group, while the control group (C) received only vehicle. Urine samples were hydrolyzed and individual estrogens were separated by celite chromatography prior to immuno-assay. Both the Tx and C groups exhibited similar urinary excretion levels of estrone (E1), E2, and E1C prior to Ovx (Pre-Ovx) and after Ovx (Post-Ovx), but there were significant differences between groups after treatment (Post-Tx). Significant differences were observed in the Tx group's excretion of E1, E2, and E1C in the Pre- vs. Post-Ovx samples and in the Post-Ovx and Post-Tx samples. The C group also showed the expected significant differences in the Pre- vs. Post-Ovx samples, as well as in the Pre-Ovx and Post-Tx samples. The results indicate that the use of E1C measurements is clearly a suitable method for monitoring ovarian function in intact, cycling animals, but urinary E2 measurements are required to verify loss of follicular activity.

Synaptic Estrogen Receptor-α Levels in Prefrontal Cortex in Female Rhesus Monkeys and Their Correlation with Cognitive Performance

“…Serum E values and urine levels of E metabolites were measured at multiple time points. As published previously for the same animals as those examined here (Rapp et al, 2003; Shideler et al, 2003; Hao et al, 2007), OVX reduced serum and urinary E to approximately zero. Estradiol cypionate injection provided every 21 d in treated monkeys (group OVX+E) produced a rapid rise in circulating E compared with V-treated animals (group OVX+V), which peaked within 24 h at levels comparable with preovulatory values in intact females, followed by decline to baseline over the next several days.…”

Estrogen Alters Spine Number and Morphology in Prefrontal Cortex of Aged Female Rhesus Monkeys

“…Serum 17␤-estradiol values were measured 1 d before treatment and 9 h, 2 d, and 3 d after treatment, and urine levels were measured at multiple time points. As detailed previously for the same animals as those examined here (P. R. Shideler et al, 2003), OVX reduced serum and urinary 17␤-estradiol to near zero. Estradiol cypionate injection provided every 21 d in treated monkeys (group OVXϩE) produced a rapid rise in circulating 17␤-estradiol compared with vehicle-treated animals (group OVXϩVeh), which peaked within 24 h at levels comparable with preovulatory values in intact females, followed by decline to baseline over the next several days.…”

“…Given this background, we have initiated a multidisciplinary analysis of 17␤-estradiol treatment in aged rhesus monkeys that employs cyclical delivery of 17␤-estradiol to monkeys that were ovariectomized relatively early during the course of aging (mean age of 22 years), before the onset of pronounced ovarian deficiency and cognitive impairment that might prove refractory to rescue (P. R. Shideler et al, 2003). Our previously published behavioral analyses of these animals (P. R. showed that this cyclical regimen of estradiol treatment reversed the most well established signature of cognitive aging in ovariectomized monkeys, the delayed response (DR) task, a behavioral assessment that critically requires the dorsolateral PFC (P. R. .…”

Effects of estrogen replacement therapy on cholinergic basal forebrain neurons and cortical cholinergic innervation in young and aged ovariectomized rhesus monkeys

“…The collective urinary metabolites of estradiol and estrone (estrone conjugates, E1C) and progesterone PdG) were measured by the immunoenzyme assays described by Shideler et al (2001), whereas total urinary estradiol was measured after hydrolysis by radioimmunoassay as previously described (Shideler et al, 2003). Briefly, urine was diluted in distilled water assayed directly for E1C and PdG.…”