Estrogen replacement in ovariectomized rats results in physiologically significant levels of circulating progesterone, and co-administration of progesterone markedly reduces the circulating estrogen

Abstract

Estrogen and progesterone replacement in ovariectomized rats in an often-used experimental system for determination of the specific effects of these hormones. In this study, two different delivery systems and two different dosage levels of estrogen, progesterone or a combination of the two have been used. Estrogen and progesterone in the circulation have been measured in response to each treatment. It is reported that estrogen treatment (237.2 +/- 49.2 pg/mL) results in physiologically significant levels of circulating progesterone (11.1 +/- 1.3 ng/mL). Also, co-administration of progesterone (23.7 +/- 2.0 ng/mL) with estrogen decreases the level of estrogen over that seen with estrogen alone (96.7 +/- 19.2 pg/mL with progesterone vs 237.2 +/- 49.2 pg/mL without progesterone). Thus, contrary to expectations, estrogen replacement therapy is not specific to estrogen and some of the antagonistic effects of progesterone are the result of a decrease in circulating estrogen, and not a specific effect on a target tissue. Whereas the mechanism of these effects has not been determined, obvious artifactitous phenomena have been excluded as being their cause. These results could have a major impact on the interpretation of past and future experiments of this kind.

Substantial discrepancies in 17β‐oestradiol concentrations obtained with three different commercial direct radioimmunoassay kits in rat sera

“…A lowering of the obtained values by approximately 20-30% was observed. This comparatively slight decrease is not consistent with the current study, and the explanations for this could possibly be found in differences in the extraction procedure, which regrettably is not explicitly described in the previous study [2]. In another study three direct 17β-estradiol RIAs (none of the ones used in the current study) were tested in human serum samples with and without organic solvent extraction.…”

“…These kits offer a fast and convenient way of measuring 17β-estradiol and are also frequently employed in rat models [2][3][4][5][6][7][8][9][10].…”

Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement

“…Progesterone is also anti-inflammatory under some circumstances, contributing to tolerance of the embryo during pregnancy (Zhao et al 2002), and likewise testosterone has been shown to reduce some immune responsivity . A previous study in our laboratory demonstrated that E 2 replacement in OVX animals resulted in physiological levels of circulating progesterone (Liu et al 1997). Kinetic analyses conducted by Shimizu et al (1993) demonstrated that natural estrogens, like estrone and estradiol, inhibit the process of androgen aromatization.…”

“…In addition, glucocorticoids are antiinflammatory and OVX has been shown to decrease glucocorticoid secretion and E 2 replacement to increase it (Lo et al 2000, Seale et al 2004. Remembering that OVX increased and E 2 replacement decreased the DTH response, one might suggest therefore that the conversion of E 2 to 2-hydroxyestrogens, the stimulatory effect of E 2 on progesterone production by the adrenal gland (Liu et al 1997), E 2 inhibition of aromatase activity in extra-ovarian tissues (Shimizu et al 1993), or E 2 stimulation of glucocorticoid secretion (Lo et al 2000, Seale et al 2004) may contribute in some measure to the effects observed. To begin to unravel these complex possibilities, the current study has used the observed different degrees of DTH response in males and females, and manipulation of the latter by OVX and E 2 replacement, to uncover important hormonally regulated cytokines, which by their pattern may indicate a significant regulatory role.…”

“…5-22 pg/ml in males (Hilakivi-Clarke et al 1996, 1997 and vary between w22 and 55 pg/ml in females, according to the stage of the estrous cycle (Walmer et al 1992). In OVX animals, previous work from this laboratory has shown that levels of E 2 are w25 pg/ml at 17 days and w30 pg/ml at 24 days post-OVX (Liu et al 1997). The E 2 replacement pellets used result in circulating blood levels of 100-200 pg/ml for a mouse weighing 20-25 g. These levels of E 2 are within the physiological range and comparable with levels found during pregnancy (Jacquet et al 1977, Parkening et al 1978.…”