Circulating gonadal steroid hormones regulate estrogen receptor mRNA in the male rat forebrain

Lisciotto, Christine A.; Morrell, Joan I.

doi:10.1016/0169-328x(93)90112-3

Cited by 54 publications

(29 citation statements)

References 60 publications

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“…Down-regulation of ERα by E2 has been demonstrated in several species by injecting E2, usually in large amounts, to ovx females [11, 21, 24, 25, 26, 28, 30, 67, 76, 77]. Few studies have been made comparing intact vs. ovx animals to assess if endogenous estrogen exerts a regulatory role on the population of ERα.…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical Detection of Estrogen Receptor-α in the Female Rabbit Forebrain: Topography and Regulation by Estradiol

et al. 2003

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Two antibodies (H222 and Zymed) directed towards different sites of the estrogen receptor-α (ERα) were used for the following objectives: (1) to map the ERα in the forebrain of ovariectomized (ovx) rabbits by immunocytochemistry and (2) to determine the effect of endogenous (intact non-pregnant animals) and exogenous (ovx, estrogen-treated animals) estradiol (E2) on the population of ERα in the forebrain. Similar results were obtained with both antibodies used: dense aggregations of ERα-immunoreactive (IR) neurons were found in the infundibular nucleus (IN), the medial preoptic area (POA), the bed nucleus of the stria terminalis (BNST), and some nuclei of the amygdala. By contrast, no ERα-IR neurons were present in the ventromedial hypothalamic nucleus (VMN), but a dense aggregation of ERα-IR neurons occurred lateral to it in nucleus X. Numerous ERα-IR neurons were observed in the paraventricular hypothalamic nucleus, but not in the supraoptic or suprachiasmatic nuclei. The hippocampus proper lacked ERα-IR neurons, but the ventral subiculum in the hippocampal formation had a dense group of such cells. Intact non-pregnant rabbits showed less ERα-IR neurons in all regions tested than ovx animals. This difference was particularly clear in the medial POA, amygdala and BNST, while the IN showed only a marginal decrease. The dorsal, but much less the ventral, part of nucleus X also showed a decrease in the number of ERα-IR neurons compared with ovx animals. E2 benzoate (5 µg/day for 5 days) reduced even further the number of ERα-IR neurons in all regions except in a circumscribed area of the IN and the ventral part of nucleus X. These results show the existence of both sensitive and insensitive neurons to the down-regulatory effect of E2 on the presence of ERα. Sensitive neurons are located in the telencephalon, POA and several hypothalamic nuclei (PVN), while insensitive neurons are mainly restricted to the IN and the ventral part of nucleus X in the basal hypothalamus.

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Section: Discussionmentioning

confidence: 99%

Immunocytochemical Detection of Estrogen Receptor-α in the Female Rabbit Forebrain: Topography and Regulation by Estradiol

et al. 2003

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“…Neuro transmitter inputs to steroid target cells [1][2][3][4] as well as effects of the steroid hormones themselves [5][6][7] roid receptor concentrations. The extent of the contribu tions made by each of these factors, however, remains illdefined, due in part to the lack of suitable methods to measure steroid hormone receptor levels in individual groups of steroid target neurons under physiological con ditions of steroid hormone secretion [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…5a-dihydrotestosterone (DHT), selectively suppresses estro gen receptor binding in the ventromedial nucleus (VMN) of the hypothalamus [8]. The effects of estrogen are more widespread: estrogen receptor mRNA levels decline in many regions of the brain after treatment with estradiol [5][6][7], Under physiological circumstances, however, the extent and direction of estrogen receptor regulation by gonadal steroids remain uncertain. In cycling female rats, Shughrue et al [10] have demonstrated that estrogen receptor mRNA levels decline by almost 50% in the medial preoptic nucleus at proestrus.…”

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Regulation of Estrogen Receptor Concentrations in the Rat Brain: Effects of Sustained Androgen and Estrogen Exposure

et al. 1996

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To determine whether estrogen and androgens either alone or in combination downregulate estrogen receptors in the brain, ovariectomized/adrenalectomized female rats received one of the following four treatments: (1) one subcutaneously placed Silastic capsule containing 10% estradiol in cholesterol, (2) one capsule containing 10% estradiol and two capsules containing 100% 5α-dihydrotestosterone (DHT), (3) two capsules containing DHT, or (4) empty Silastic capsules (control animals). Animals were killed 4 or 8 days after capsule insertion and the occupied, unoccupied and total estrogen receptor content in specific brain nuclei was determined by quantitative in vitro autoradiography. To determine if the effects of the androgen were reversible, DHT capsules were removed after 4 days from half of the estradiol + DHT-treated rats, and the animals were killed 4 days later. Estradiol downregulated estrogen receptor expression in the periventricular preoptic area, medial preoptic area, bed nucleus of the stria terminalis (BNST), arcuate nucleus (ARC), ventromedial nucleus (VMN), and medial and cortical amygdala, decreasing receptor content by 30–41 % in animals treated for 4 days, and by 44-60% in animals treated for 8 days with estradiol alone. DHT treatment in combination with estradiol further decreased estrogen receptor content in the BNST, ARC and VMN, relative to the estradiol-only animals. DHT in the absence of estrogen was without effect. In animals in which the DHT capsules were removed after 4 days of exposure, allowing the estradiol to remain for a further 4 days, estrogen receptor levels were indistinguishable from those measured in control animals treated for 8 days with estradiol alone. These results demonstrate that sustained estrogen exposure downregulates levels of estrogen receptor in the brain and confirm that DHT synergizes with estrogen in inducing this response in some, but not all, target neuronal groups.

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“…Brain ERα levels may also be affected by other steroids released by the ovary. Thus, estrogen binding in the hypothalami of ovariectomized (OVX) rats is reduced following administration of progesterone (P) [5], the nonaromatizable androgen dihydrotestosterone [6], or E 2 [7], while testosterone (T) [8] has been shown to downregulate hypothalamic ERα mRNA expression.…”

Section: Introductionmentioning

confidence: 99%

In vitro<b> </b>Autoradiographic Analysis of Regional Changes in Estrogen Receptor Alpha in the Brains of Cycling Female Rats

Bowlby

Brown²,

Hochberg³

et al. 2015

Neuroendocrinology

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Background/Aims: The contributions of the three principal ovarian steroid hormones (estradiol, progesterone and testosterone) to the regulation of estrogen receptor alpha (ERα) levels in the rat brain were examined during the estrous cycle. Methods: Receptor concentrations were measured using an in vitro autoradiographic technique designed to separately quantify free, unoccupied receptors and receptors ‘occupied' by (bound to) endogenous hormone. Results: ERα occupation increased at proestrus and declined at estrus, reflecting changes in circulating estradiol and testosterone levels. Total ERα content followed a pattern that was the inverse of the occupation data, falling over the night of proestrus. Between 2.00 and 10.00 a.m. on the day of estrus, total ERα concentrations recovered in all brain regions except the ventromedial nucleus (VMN), in which ERα binding remained depressed at estrus. Administration of the progesterone antagonist mifepristone on the afternoon of proestrus resulted in recovery of ERα levels in the VMN by the morning of estrus, consistent with the hypothesis that the preovulatory progesterone surge selectively inhibits VMN ERα expression. Residual ERα occupation observed at estrus, when estradiol is not detectable in the serum, likely reflects intracranial aromatization of circulating androgens, since the pattern of receptor occupation observed at this stage of the cycle could be reproduced in ovariectomized rats by replacement with testosterone. Conclusion: These findings indicate that ERα binding in the brain fluctuates during the rat estrous cycle in a region-specific manner and suggest that local aromatization of testosterone may contribute significantly to ERα occupation when circulating estradiol levels are low.

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Circulating gonadal steroid hormones regulate estrogen receptor mRNA in the male rat forebrain

Cited by 54 publications

References 60 publications

Immunocytochemical Detection of Estrogen Receptor-α in the Female Rabbit Forebrain: Topography and Regulation by Estradiol

Immunocytochemical Detection of Estrogen Receptor-α in the Female Rabbit Forebrain: Topography and Regulation by Estradiol

Regulation of Estrogen Receptor Concentrations in the Rat Brain: Effects of Sustained Androgen and Estrogen Exposure

In vitro<b> </b>Autoradiographic Analysis of Regional Changes in Estrogen Receptor Alpha in the Brains of Cycling Female Rats

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