Concentrations of circulating steroids in normal prepubertal and adult male and female humans, chimpanzees, rhesus monkeys, rats, mice, and hamsters: A literature survey

Overpeck, James; Colson, Sylvia H.; Hohmann, John R.; Applestine, Marshall S.; Reilly, Joseph

doi:10.1080/15287397809529700

Cited by 84 publications

(46 citation statements)

References 130 publications

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“…Furthermore, the effects of P are dependent on the concentration of estrogens in a variety of physiological events. But the serum concentration of E 2 in rats is lower than that in humans [22] in contrast to the case for P. Thus it is possible that the species differences in the effects of progestins between rats and humans might become apparent when the concentrations of estrogens were decreased after ovariectomy or menopause, even though the differences were not prominent under the conditions of the normal reproductive cycle.…”

Section: Discussionmentioning

confidence: 62%

“…However, we are unaware of the exact mechanism underlying the species differences in the effects of progestins. We can consider the following possibilities: First, the serum concentration of P in rats is generally remarkably higher than that in humans, and this holds true even after ovariectomy [22]. Therefore the contribution of the reduction in serum P concentration after ovariectomy to the change of thermoregulation might be less in rats, compared with humans.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Kobayashi

Tamura²,

Hayashi³

et al. 2000

JJP

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Menopausal hot flushes (HFs) are the major climacteric symptoms and occur in most climacteric women [1,2]. This symptom manifests as a transient increase in skin temperature in the face and peripheral parts of the extremities. The cause of the occurrence of HFs is the cessation of the ovarian production of sex hormones (i.e., estrogens and progestins) after menopause; and estrogens, especially estradiol (E 2 ), are considered to be the main factors responsible for generating HFs [3,4]. Thus estrogens are the primary agent for hormone replacement therapy for climacteric women, whereas progestins are commonly used with estrogens for inhibiting the side effects of estrogens on the uterus. However, only a single administration of progesterone (P) or its analogue has been reported to be effective for the treatment of HFs with almost the same efficacy as those of estrogens [5][6][7][8][9]. This clinical evidence suggests that progesterone as well as estrogens may be important for controlling the generation of HFs.By using rat tail, which is useful for studying skin temperature regulation [10], we previously demonstrated that the tail skin temperature (TST) in female rats was elevated after ovariectomy and suggested that this thermoregulatory change, which indicated the augmentation of vasodilatory heat dissipation, was relevant to human symptoms of menopausal HFs [11,12]. In this experimental system, we also demonstrated the inhibitory effect of E 2 posttreatment on the elevation of the TST and indicated the decrease in the E 2 level to be involved in the TST elevation induced by ovariectomy [11,12]. However, because we haven't evaluated the effects of P in this model, we examined the effects of P on the elevation of the TST, starting the treatment just after the ovariectomy. Furthermore, we also examined the effects of E 2 by the same protocol as that used for P and compared the results to evaluate the degree of involvement of both ovarian hormones in the development of the TST elevation induced by ovariectomy. Materials and MethodsAnimals. Specific pathogen-free (SPF) female Sprague-Dawley rats purchased from Charles River Japan (Yokohama, Japan) were used in these experiments. The rats were housed under a 12 : 12-h light/dark cycle with lights on at 0600 h in a thermoregulated room maintained at 24.0Ϯ2.0°C. Humidity was maintained in the range of 55Ϯ10%, and food (CE-2, Clea, Tokyo, Japan) and water were provided ad libitum. A bilateral ovariectomy or sham operation was performed on the rats at the age of 11 to 12 weeks. The experimental protocols were in accordance with the regulation of the Animal Care and Use Committee of our Institute.Temperature recording. Temperature record- Key words: progesterone, tail skin temperature, ovariectomy. Abstract:We examined the effects of progesterone on the elevation of tail skin temperature (TST) in ovariectomized rats and compared them with those of estradiol. Progesterone showed only insignificant effects on the TST elevation, whereas estradiol showed complete inhibition. T...

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Kobayashi

Tamura²,

Hayashi³

et al. 2000

JJP

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“…Although we used 5-week-old mice in the peripubertal period to minimize the hormonal variability, these animals have somewhat increased circulating levels of estradiol in the high diestrous range (Overpeck et al 1978), and this may have played a role in triggering the paradoxical anxiogenic effect of THP. Further, the results from the present study may also have relevance for mood swings and irritability, commonly reported at the onset of puberty in association with fluctuations in steroid hormones (Buchanan et al 1992;Cameron 2004).…”

Section: Discussionmentioning

confidence: 99%

“…These animals do not exhibit estrous cyclicity and were used in order to isolate selective effects of THP withdrawal on behavioral state. Circulating levels of estradiol at this time are increasing to within the high diestrous range (Overpeck et al 1978) and are elevated above levels earlier in development. Additional δ knockout mice were bred in-house, and tails genotyped after experimental procedures were completed.…”

Section: Animalsmentioning

confidence: 93%

Steroid withdrawal in the mouse results in anxiogenic effects of 3α,5β-THP: a possible model of premenstrual dysphoric disorder

et al. 2005

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Rationale-3α-OH-5α[β]-pregnan-20-one (THP) is a positive modulator of the GABA A receptor (GABAR), which underlies its reported anxiolytic effect. However, there are conditions such as premenstrual dysphoric disorder (PMDD) where increases in THP levels can be associated with adverse mood.Objectives-In order to test for conditions where THP might be anxiogenic, we developed a mouse model of THP withdrawal. Because δ-containing GABAR are highly sensitive to THP modulation, results were compared in wild-type and δ knockout mice.Methods-Finasteride, a 5α-reductase blocker, was administered for 3 days to female wild-type or δ knockout mice. Then, animals were tested in the elevated plus maze, following acute administration of THP, lorazepam, flumazenil, or 4,5,6,pyridin-3-ol (THIP), and results compared to vehicle-injected controls. CA1 hippocampal GABAR α4 subunit levels were assessed by Western blot.Results-After THP withdrawal, THP produced anxiogenic effects, decreasing open arm entries on the elevated plus maze, following a brief shock, in contrast to its expected anxiolytic effects. As we have shown in rats, THP withdrawal also resulted in increased expression of the α4 subunit in mouse CA1 hippocampus. As expected for increases in α4-containing GABAR, THP withdrawn mice were relatively insensitive to the benzodiazepine (BDZ) lorazepam and had atypical responses to the BDZ antagonist flumazenil when tested on the plus maze. In contrast, they showed a greater anxiolytic response to THIP, which has greater efficacy at α4βδ than other GABAR. Although THP Correspondence to: Sheryl S. Smith, Sheryl.smith@downstate.edu. NIH Public AccessAuthor Manuscript Psychopharmacology (Berl) withdrawal in δ knockout mice also increased the α4 GABAR subunit, the anxiogenic effects of THP and the anxiolytic effects of THIP were not observed, implicating α4βδ GABAR in these effects.Conclusions-Based on these behavioral and pharmacological findings, we suggest that THP withdrawal in the mouse may serve as a rodent model of PMDD.

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“…However, in many commonly used and widely accepted rodent models, the utility of the measurement of circulating serum hormone levels alone as an indicator of exposure to androgen-disrupting chemicals is limited. In male laboratory mice and males of several other species, including humans, there is striking intraindividual and interindividual variability in testosterone levels (31)(32)(33)(34). Thus, it is extremely difficult to detect statistically significant differences in steroid hormone levels due to exposure to a xenobiotic.…”

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confidence: 99%

Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

Wilson

McLachlan

Falls

et al. 1999

Environ Health Perspect

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Assessment of the impact of environmental chemicals on androgen homeostasis in rodent models is confounded by high intraindividual and interindividual variability in circulating testosterone levels. Our goal was to evaluate changes in testosterone biotransformation processes as a measure of androgen homeostasis and as a biomarker of exposure to androgen-disrupting chemicals. Sexspecific differences in hepatic testosterone biotransformation enzyme activities were identified in CD-i mice. Gonadectomy followed by replacement of individual steroid hormones identified specific sex differences in biotransformation profiles that were due to the inductive or suppressive effects of testosterone. Notably, significant androgen-dependent differences in testosterone 6a-and 15a-hydroxylase activities were demonstrated, and the ratio of 6w and 15a-hydroxylase activities proved to be an excellent indicator of the androgen status within the animaL The male or "masculinized" testosterone 6alotISt-hydroxylase ratio was significantdy less than the female or "feminized" ratio. Male mice were exposed to both an antiandrogen, vinclozolin, and to a compound that modulates serum androgen levels, indole-3-carbinol, to test the utility of this ratio as a biomarker of androgen disruption. Treatment with the antiandrogen vinclozolin significantly increased the 6ax1l5a-hydroxylase ratio. Indole-3-carbinol treatment resulted in a dose-dependent, but highly variable, decrease in serum testosterone levels. The 6aIlSa-hydroxylase ratio increased as serum testosterone levels decreased in these animals. However, the increase in the ratio was much less variable and more sensitive than serum testosterone levels. These investigations demonstrate that the 6a/150-hydroxylase ratio is a powerfil measure of androgen modulation and a sensitive indicator of exposure to androgen-disrupting chemicals in CD-1 mice. Key work androgen disruption,.biomarker, biotransformation, sexually dimorphic metabolism, testosterone.

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Concentrations of circulating steroids in normal prepubertal and adult male and female humans, chimpanzees, rhesus monkeys, rats, mice, and hamsters: A literature survey

Cited by 84 publications

References 130 publications

Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Steroid withdrawal in the mouse results in anxiogenic effects of 3α,5β-THP: a possible model of premenstrual dysphoric disorder

Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

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