Abstract
Fluctuating sex steroids during the estrous or menstrual cycle of mammalian females make it difficult to determine their role on behaviors and physiology. To avoid this, many investigators ovariectomize their animals and administer progesterone, estradiol or a combination of both. Several different strategies are used to administer estradiol, which confounds interpretation of results. This study compared two methods of estradiol replacement implants: Silastic tubes filled with crystalline estradiol benzoate (E2) and commercially available estradiol benzoate pellets. Implants were placed subcutaneously in adult ovariectomized (OVX) rats and blood samples obtained weekly. Control OVX rats received empty Silastic tubes or placebo pellets. Our data shows that E2 plasma levels from rats with Silastic implants peaked after one week and decreased slowly thereafter. In contrast, plasma E2 from commercial pellets peaked after two weeks, increasing and decreasing over time. To validate hormone release, body weight was monitored. All E2 treated animals maintained a similar body weight over the four weeks period whereas an increase in body weight over time was observed in the OVX group that received empty implants, confirming E2 release and supporting the role of E2 in the regulation of body weight. Furthermore, the effects of E2 on basal locomotor activity were assessed using animal activity cages. Results showed no difference between E2 and control group in several locomotor activities. These results indicate that Silastic implants achieve more stable plasma estradiol levels than pellets and thus are a better alternative for studies of estradiol on brain function and behavior.
Highlights
Estrogens are a family of steroid hormones derived from cholesterol that include estrone, estriol, and estradiol
Estradiol levels of rats implanted with placebo pellets did not decline to the same extent as those that received an empty Silastic implant or no implant whatsoever, and were not significantly different than levels observed in intact females at day 0 (Figure 1 and Table 1)
Our results show that Silastic implants provide a more stable delivery system of estradiol than the commercially available pellets, i.e., delivery by pellets fluctuated significantly from week to week
Summary
Estrogens are a family of steroid hormones derived from cholesterol that include estrone, estriol, and estradiol. Estradiol is the most abundant sex steroid in pre-menopausal woman and has the highest estrogenic activity. Estradiol is produced mainly in the ovaries and to a lesser extent, by the adrenal cortex. Several tissues, such as the brain, produce estradiol for local use, mainly by aromatization of androgens to estradiol. Estradiol's effects are exerted mainly by binding to intracellular receptors. The hormone-receptor complex binds to specific sites on the DNA (estrogen response elements) and activates or represses transcription of target genes. Interact, with membrane receptors, and modulate aperture of ionic channels or promote activation of second messenger systems, resulting in a faster response [1]. The membrane receptor, GPER ( known as GPR30), a 7 transmembrane G-protein coupled receptor that binds estradiol, was recently described to mediate many of estradiol's rapid effects [1]
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