Biol Reprod
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hileman, S. M.
Right arrow Articles by Jackson, G. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hileman, S. M.
Right arrow Articles by Jackson, G. L.
Agricola
Right arrow Articles by Hileman, S. M.
Right arrow Articles by Jackson, G. L.
Biology of Reproduction 60, 1279-1284 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Articles

Distribution of Estrogen Receptor-ß Messenger Ribonucleic Acid in the Male Sheep Hypothalamus1

Stanley M. Hileman2,a, Robert J. Handa3,b, and Gary L. Jacksona

a Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois 61802 b Department of Cell Biology, Neurobiology, and Anatomy, Loyola University-Chicago, Maywood, Illinois 60153


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
As a first step in determining possible influences of the newly discovered estrogen receptor (ER)-ß on reproduction, we have localized mRNA for ER-ß within the male sheep hypothalamus using in situ hybridization and a rat ER-ß cRNA probe. Highest amounts of hybridization signal were observed in the preoptic area (POA), bed nucleus of the stria terminalis, paraventricular nucleus, and supraoptic nucleus. Relatively moderate amounts of hybridization signal were observed in the retrochiasmatic area (RCH), anterior hypothalamic area, dorsomedial hypothalamus, and lateral hypothalamus. Only a low level of hybridization signal was observed in the ventromedial hypothalamus, suprachiasmatic nucleus, and arcuate nucleus. The presence of ER-ß mRNA in several areas of the male sheep hypothalamus suggests multiple functions for this receptor. The distribution of ER-ß in the ovine hypothalamus was similar to that described for the rat, suggesting a high degree of functional conservation across species. A role for ER-ß in influencing reproduction is suggested by its presence in the POA and RCH, regions of the hypothalamus that control reproduction.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Until recently, the multiple actions of estrogen were believed to be mediated by only one form of estrogen receptor, the alpha isoform (ER-{alpha}). Accordingly, much effort has been expended mapping and characterizing the role that ER-{alpha} plays in physiological processes, including reproduction. However, the concept of a single receptor seemed inconsistent with the fact that other members of the nuclear receptor superfamily display multiple receptor subtypes [1] and that the effects of synthetic estrogens, antiestrogens, and their analogues differ markedly in different target cells and tissues [2]. A signal advance in the field occurred with the production of a transgenic mouse model lacking a functional ER-{alpha} [3]. Interestingly, some tissues in these animals still displayed a residual amount of estrogen binding. This finding, along with the observation that hypothalamic progesterone receptor mRNA is up-regulated by estrogen in these mice [4], implied the existence of another form of estrogen receptor.

A second form of the estrogen receptor, termed ER-ß, was cloned recently from prostate and ovary tissue [5]. This isoform specifically binds estrogen, although it does so with about 4-fold less affinity than ER-{alpha} [6]. However, the role of ER-ß in regulating hypothalamic function is as yet unknown. We previously showed that estrogen acts in the male sheep hypothalamus to inhibit pulsatile LH release, presumably through reduction of LHRH secretion [7]. While some if not all of these actions may be due to interaction with ER-{alpha}, the presence of ER-ß in the rat hypothalamus [8] raises the possibility that this most recently discovered form of the ER also may be involved in regulating LHRH release. In an initial step to determine the possible role of ER-ß and to extend the current information to another species, we have used in situ hybridization to localize ER-ß mRNA within the male sheep hypothalamus.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
General

Four male sheep that were of predominantly Suffolk breeding and had been castrated for at least 6 mo were used. These animals were part of another study [9] wherein they were moved indoors during December and exposed to 90 days of long days (16L:8D) followed by 90 days of short days (10L:14D). At the end of this second artificial photoperiod, they were killed with an overdose of barbiturate and the hypothalami were excised within 10 min. Tissue was frozen on dry ice and stored at -70°C until sectioned at a thickness of 16 µm on a cryostat and used for in situ hybridization. This study was carried out at the University of Illinois Urbana-Champaign with approval of the Institutional Animal Care and Use Committee and in accordance with the guidelines for animal research of the National Institutes of Health.

In Situ Hybridization

In situ hybridization was performed using sense or antisense cRNA probes. Probes were transcribed from a polymerase chain reaction-generated transcription template corresponding to nucleotides 1183 to 1614 of the rat ER-ß sequence. Antisense cRNA probes were transcribed using SP6 RNA polymerase in the presence of 50 µM [35S]UTP. Sense cRNA probes were transcribed using T7 RNA polymerase. Completeness of transcription was determined using polyacrylamide gel electrophoresis (5% acrylamide, 7.5% urea). These probes have been described previously [10]. Frozen tissue sections were thawed and then fixed in 4% buffered formalin for 5 min, acetylated with acetic anhydride (0.25% in tetraethylammonium), delipidated in chloroform, and hybridized at 57°C overnight in buffer (50% formamide, 20% dextran sulfate, 600 mM NaCl, 20 mM Tris, 0.04% Denhardt's, 2 mM EDTA, 0.02% salmon sperm DNA, 0.01% yeast tRNA, 0.1% sodium thiosulfate, 100 mM dithiothreitol, 0.1% SDS) containing 1.5 x 107 cpm/ml probe. This working concentration of probe was shown to be saturating using rat brain sections. After hybridization, sections were treated with RNase A (20 µg/ml at 37°C for 30 min) and washed to a final stringency of 57°C, 0.1-strength SSC (single-strength SSC is 0.15 M sodium chloride and 0.015 M sodium citrate). Sections were dried and apposed to x-ray film (Hyperfilm betamax; Amersham, Lake Forest, IL) for 10 days to obtain initial images and then coated with photographic emulsion (NTB-3; Eastman Kodak, Rochester, NY) and allowed to expose for 4 wk. Slides were developed in Kodak D-19 developer, counterstained with cresyl violet, dehydrated, and coverslipped using Permount (Fisher Scientific, Pittsburgh, PA).

Analysis

Slides were scanned under low-power magnification using a Zeiss (Carl Zeiss, Thornwood, NY) microscope to identify areas of signal localization. Areas then were examined under brightfield illumination to ascertain that signal was localized over cell nuclei. Degree of labeling assigned to specific areas was based on visual inspection and comparison under darkfield illumination, and thus differences in intensity (Table 1) are meant to be relative and qualitative and not quantitative. Photomicrographs were taken at x5 or x10 magnification using the same type of microscope, and these images were scanned into Adobe Photoshop (Mountain View, CA). Brightness and contrast were adjusted in order to make the digital image comparable to that seen through the microscope. This in no way compromised the data. Areas of localization were identified with the aid of diagrams of the ovine hypothalamus from Lehman et al. [11] and comparison with figures of rat neuroanatomy from Paxinos and Watson [12].


View this table:
[in this window]
[in a new window]
  		TABLE 1. Relative intensity of hybridization signal for ER-ß mRNA in specific regions of the male sheep hypothalamus.a


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Relative levels of hybridization signal with regard to specific hypothalamic areas are summarized in Table 1. Heaviest expression of signal was evident in the preoptic area (POA), bed nucleus of stria terminalis (BNST), paraventricular nucleus (PVN), and the supraoptic nucleus (SON). Intermediate levels of hybridization signal were detected in the retrochiasmatic area (RCH). Lower but still obvious levels of signal were seen in the lateral hypothalamic area (LHA), anterior hypothalamic area (AHA), and dorsomedial hypothalamus (DMH). There was only sparse labeling of the suprachiasmatic nucleus (SCN), ventromedial nucleus (VMN), and arcuate nucleus (ARC). Photomicrographs from a representative animal for specific areas are shown in Figures 1–3.



View larger version (64K):
[in this window]
[in a new window]
  		FIG. 1. Darkfield photomicrographs of specific regions of male ovine hypothalamus. Sections were exposed to either an antisense cRNA ER-ß probe (AHA, DMH, RCH) or a sense probe (POA-sense) corresponding to nucleotides 1183 to 1614 of the rat ER-ß sequence. 3V, Third ventricle; OT, optic tract. AHA, DMH, and POA are at a x5 magnification. RCH is at a x10 magnification in order to more easily visualize the area known to contain A15 dopaminergic neurons. Borders of the tissue and relevant structures are outlined by dashed lines.



View larger version (65K):
[in this window]
[in a new window]
  		FIG. 2. Darkfield photomicrographs of specific regions of the male sheep hypothalamus exposed to an antisense cRNA ER-ß probe corresponding to nucleotides 1183 to 1614 of the rat ER-ß sequence. 3V, Third ventricle. Borders of the tissue and relevant structures are outlined by dashed lines. x5 (reproduced at 90%).



View larger version (79K):
[in this window]
[in a new window]
  		FIG. 3. Darkfield photomicrographs of specific regions of the male sheep hypothalamus, exposed to an antisense cRNA ER-ß probe corresponding to nucleotides 1183 to 1614 of the rat ER-ß sequence, are shown in the upper panels. x5. A brightfield photomicrograph of a single hybridized neuron in the POA is shown in the lower panel at x100. Abbreviations: 3V, third ventricle; OC, optic chiasm; OVLT, organum vasculosum lamina terminalis. Borders of tissue and relevant structures are shown by dashed lines. Reproduced at 90%.

Only background level of signal was evident on tissue to which the sense form of the ER-ß probe was applied (Fig. 1).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This study shows that ER-ß mRNA is present in the male sheep hypothalamus. Furthermore, distribution of ER-ß mRNA is limited to specific nuclear regions, some of which undoubtedly influence reproduction. While some overlap exists, this distribution is different from known locations of ER-{alpha} in female sheep. Distribution of ER-ß mRNA in the male sheep hypothalamus was for the most part similar to that described for the rat, suggesting similar, conserved functions for this receptor between species.

Our previous work [7] showed that estrogen acted in the ARC/ventromedial region of the hypothalamus to reduce pulsatile LH release but was without obvious effect in the POA. In the present study we observed heavy localization of signal in the POA, but little signal in the ARC or ventromedial hypothalamus (VMH). On the basis of these results, it seems unlikely that estrogen alters LHRH, and thus LH, release by acting through ER-ß in either the ARC or VMH. However, the possibility cannot be excluded that ER-ß-containing cells in the POA project to the ARC/median eminence region and may thereby influence LHRH release. A similar type of projection has been observed for ER-{alpha}-containing cells in the female sheep [13]. We view this as unlikely, however, since estrogen implants in the POA in our earlier study [7] failed to alter LHRH release. Nonetheless, as is the case for ER-{alpha} [14], if ER-ß does influence LHRH release it likely does so in an indirect manner, as LHRH neurons in the rat possess little, if any, ER-ß [15].

The RCH of the hypothalamus contained moderate levels of signal. This region of the sheep hypothalamus includes a cluster of dopamine-containing neurons, termed the A15 group. In female sheep, lesions of this area reduce the ability of estrogen to inhibit LH secretion [16, 17], and administration of estrogen activates A15 neurons, as indicated by the induction of c-Fos, in a season-specific manner [18]. This region is much less characterized in male sheep, but we showed previously that testosterone induces c-Fos in A15 neurons in association with reduced LH release during long-day photoperiods [19]. It was heretofore thought that effects of estrogen or testosterone on these cells were indirect, as they contain little ER-{alpha} [14] or androgen receptor [20]. However, our findings are consistent with the possibility that the actions of estrogen in the female, or testosterone in the male (via aromatization to estrogen), on these cells in sheep may be mediated via ER-ß. Further work will be necessary to determine whether dopamine-containing cells in this region also contain ER-ß.

In addition to observations in the areas discussed above, heavy amounts of signal were identified in the PVN and SON. This finding may have several implications. First, ER-ß may be involved in regulating water balance. Estrogen influences osmotic balance by influencing PVN/SON vasopressin activity [21–23]. Consistent with this idea, Hrabovsky et al. [24] reported that in rats, both oxytocin- and vasopressin-containing neurons in these areas express mRNA for ER-ß, a finding in accord with our observation that PVN vasopressin neurons express ER-ß (unpublished results). Second, ER-ß may be involved in mediating responses to stressors. Estrogen enhances adrenocorticotropin hormone and corticosterone responses to stressors [25]. Since vasopressin is a stimulator of adrenocorticotropin hormone, which enhances the actions of corticotropin-releasing hormone [26, 27], it seems plausible that estrogen, acting through ER-ß-containing vasopressin cells, might influence the response to stress. Third, estrogen, acting through ER-ß, may influence timing of parturition by influencing PVN oxytocin activity [28, 29]. Fourth, estrogen, acting through ER-ß, may influence other functions of the PVN by altering levels of peptides such as galanin, dynorphin, and angiotensin II in vasopressin cells [30]. These possible interpretations are advanced with caution, as they are based on the assumption that the PVN and SON function similarly in rodents and sheep. However, given the fact that these areas contain little ER-{alpha} in the sheep, our observations support the idea that any effects of estrogen on PVN/SON neuronal function in sheep are likely mediated by ER-ß.

One question that arises owing to its obvious implications for ER-ß function is to what degree this form of the receptor interacts with ER-{alpha}. Distribution of ER-{alpha} in the male sheep has not been characterized previously. In contrast, distribution of ER-{alpha} in female sheep has been reported [11]. Since distribution of ER-{alpha} in males and females appears similar, at least in rodents [31, 32], it seems reasonable to compare our ER-ß data to ER-{alpha} distribution in female sheep. Upon doing so it becomes obvious that there are areas of distribution unique to each receptor subtype. The VMH and ARC contain heavy concentrations of ER-{alpha} but contain little ER-ß. Conversely, the PVN, SON, and RCH contain high to moderate amounts of ER-ß but little ER-{alpha}. This suggests that these receptors influence different hypothalamic functions. This also implies that although limited homology exists between ER-{alpha} and ER-ß in the genetic region to which the probe is directed, binding of the rat ER-ß probe to ovine tissue was specific for ER-ß. While it is clear that distinct areas of distribution exist, it is equally obvious that a great deal of overlap exists in their respective distributions (i.e., POA, AHA, BNST), raising the possibility of an interaction of ER-{alpha} and ER-ß in these areas. This seems plausible given the fact that ER-{alpha} and ER-ß form heterodimers in vitro [33–35]. Indeed, it has been suggested that ER-ß actually may act in a manner opposite that of ER-{alpha} [36]. This supposition is based, at least in part, on the finding that when complexed with estradiol and an activator protein-1 response element, ER-{alpha} initiates whereas ER-ß inhibits transcription. Differences in regulation of intracellular activity or pathways by ER-{alpha} and ER-ß homo- and heterodimers greatly expand the scope of conceptual mechanisms whereby estrogen regulates cell function. However, it remains to be seen whether these two subtypes exist within the same cell in vivo. Resolving the critical issue of ER-{alpha} and ER-ß interaction and their collective influence on intracellular function will require further work.

In general, the pattern of ER-ß mRNA distribution observed in our study appeared to be similar to that described for rodents [8]. In both species, heaviest amounts of signal occurred in the PVN, SON, POA, and BNST. Similarly, moderate labeling was observed in the DMH, LHA, and RCH, and only sparse labeling was observed in the VMN or ARC. In apparent contrast with work in the rat, we observed virtually no signal in the SCN, and level of signal appeared noticeably heavier in the DMH and RCH than reported for the rat. While differences in technique mandate caution in interpreting the comparison between species, the widespread distribution of ER-ß mRNA implies that this receptor may influence several important physiological functions. In addition, the marked similarity in distribution between the rat and sheep hypothalamus seems to indicate that ER-ß-mediated processes are similar and conserved among differing mammalian species.

In summary, ER-ß mRNA was identified in several hypothalamic regions, some of which are important for reproduction. The widespread distribution of ER-ß in the male sheep hypothalamus would suggest that ER-ß has numerous and diverse functions. Some of these areas, such as the POA and RCH, are known to be involved in regulating reproductive function. Comparison with the known distribution of ER-{alpha} would indicate both unique functions for, and an interplay of, ER-{alpha} and ER-ß isoforms. While these findings represent an important first step in defining possible functions for ER-ß in the hypothalamus, clearly more work will be necessary to determine the importance of this recently discovered receptor in controlling hypothalamic function, and in particular, reproduction.


   ACKNOWLEDGMENTS
 
The authors would like to thank Dr. Clifford Saper for use of his microscope equipment and Drs. Joel Elmquist, Carol Elias, and Rexford Ahima for their help with the photomicrographs and digital imaging. We also appreciate the help of Dr. Laura Lubbers for her constructive critique of this manuscript and the technical assistance of Melanie Bollnow.


   FOOTNOTES
 
1 This work was supported by USDA Grant AG95–37203–2033 to G.L.J. Back

2 Correspondence and current address: Stan Hileman, 325 Research North, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Ave., Boston, MA 02215. FAX: 617 667 2927; shileman{at}caregroup.harvard.edu Back

3 Current address: Robert J. Handa, Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO 80523. Back

Accepted: January 5, 1999.

Received: October 5, 1998.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Tsai M-J, O'Malley BW. Molecular mechanism of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 1994; 63:451–486.[CrossRef][Medline]
  2. Katzenellenbogen JA, O'Malley BW, Katzenellenbogen BS. Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell- and promoter-specific action of these hormones. Mol Endocrinol 1996; 10:119–131.[CrossRef][Medline]
  3. Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies OS. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 1993; 90:11162–11166.[Abstract/Free Full Text]
  4. Shughrue PJ, Lubahn DB, Negro-Vilar A, Korach KS, Merchenthaler I. Responses in the brain of estrogen receptor {alpha}-disrupted mice. Proc Natl Acad Sci USA 1997; 94:11008–11012.[Abstract/Free Full Text]
  5. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J-A. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996; 93:5925–5930.[Abstract/Free Full Text]
  6. Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggblad H, Nilsson S, Gustafsson J-A. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors {alpha} and ß. Endocrinology 1997; 138:863–870.[Abstract/Free Full Text]
  7. Scott CJ, Kuehl DE, Ferriera SA, Jackson GL. Hypothalamic sites of action for testosterone, dihydrotestosterone, and estrogen in regulation of luteinizing hormone secretion in male sheep. Endocrinology 1997; 138:3686–3694.[Abstract/Free Full Text]
  8. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-{alpha} and -ß mRNA in the rat central nervous system. J Comp Biol 1997; 388:507–525.
  9. Hileman SM, Kuehl DE, Jackson GL. Photoperiod affects the ability of testosterone to alter proopiomelanocortin mRNA, but not luteinizing hormone-releasing hormone mRNA levels in male sheep. J Neuroendocrinol 1998; 10:587–592.[CrossRef][Medline]
  10. Wilson ME, Price RH Jr, Handa RJ. Estrogen-receptor beta mRNA expression in the pituitary gland. Endocrinology 1998; 139:5151–5156.[Abstract/Free Full Text]
  11. Lehman MN, Ebling FJP, Moenter SM, Karsch FJ. Distribution of estrogen receptor-immunoreactive cells in the sheep brain. Endocrinology 1993; 133:876–886.[Abstract]
  12. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. New York: Academic Press; 1986.
  13. Jansen HT, Hileman SM, Lubbers LS, Jackson GL, Lehman MN. A subset of estrogen receptor-containing neurons project to the median eminence in the ewe. J Neuroendocrinol 1996; 8:921–927.[CrossRef][Medline]
  14. Lehman MN, Karsch FJ. Do gonadotropin-releasing hormone-, tyrosine hydroxylase-, and beta-endorphin-immunoreactive neurons contain estrogen receptors? A double-label immunocytochemical study in Suffolk ewes. Endocrinology 1993; 133:887–895.[Abstract]
  15. Laflamme N, Nappi RE, Drolet G, Labrie C, Rivest F. Expression and neuropeptidergic characterization of estrogen receptors (ER-{alpha} and ERß) throughout the rat brain: anatomical evidence of distinct roles of each subtype. J Neurobiol 1998; 36:357–378.[CrossRef][Medline]
  16. Havern RL, Whisnant CS, Goodman RL. Dopaminergic structures in the ovine hypothalamus mediating estradiol negative feedback in anestrous ewes. Endocrinology 1994; 134:1905–1914.[Abstract]
  17. Thiery J-C, Gayrard V, LeCorre S, Viguie C, Martin GB, Chemineau P, Malpaux B. Dopaminergic control of LH secretion by the A15 nucleus in anestrous ewes. J Reprod Fertil Suppl 1995; 49:285–296.[Medline]
  18. Lehman MN, Durham DM, Jansen HT, Adrian B, Goodman RL. Dopaminergic A14/A15 neurons are activated during estradiol negative feedback in anestrous, but not breeding season, ewes. Endocrinology 1996; 137:4443–4450.[Abstract]
  19. Lubbers LS, Hileman SM, Jansen HT, Lehman MN, Jackson GL. Testosterone-induced activation of tyrosine hydroxylase-containing neurons of the A14 and A15 hypothalamic nuclei in the male sheep. In: 25th Annual Meeting of the Society for Neuroscience; 1995; San Diego, CA. Abstract 745.2.
  20. Herbison AE. Neurochemical identity of neurones expressing oestrogen and androgen receptors in sheep hypothalamus. J Reprod Fertil Suppl 1995; 49:271–283.[Medline]
  21. Akaishi T, Sakuma Y. Estrogen-induced modulation of hypothalamic osmoregulation in female rats. Am J Physiol 1990; 258:R924-R929.
  22. Peysner K, Forsling ML. Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat. J Endocrinol 1990; 124:277–284.[Abstract]
  23. Barron WM, Schreiber J, Lindheimer MD. Effect of ovarian sex steroids on osmoregulation and vasopressin secretion in the rat. Am J Physiol 1986; 250:E352-E361.
  24. Hrabovsky E, Kallo I, Hajszan T, Shughrue PJ, Merchenthaler I, Liposits Z. Expression of estrogen receptor-ß messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Endocrinology 1998; 139:2600–2604.[Abstract/Free Full Text]
  25. Burgess LH, Handa RJ. Estrogen alters adrenocorticotropic hormone and corticosterone secretion and glucocorticoid receptor-mediated function. Endocrinology 1992; 131:1261–1269.[Abstract]
  26. Rivier C, Vale W. Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo. Endocrinology 1983; 113:939–942.[Abstract]
  27. Gillies GE, Linton EA, Lowry PJ. Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature 1982; 299:355–357.[CrossRef][Medline]
  28. McDonald TJ, Nathanielsz PW. Bilateral destruction of the fetal paraventricular nuclei prolongs gestation in sheep. Am J Obstet Gynecol 1991; 165:764–770.[Medline]
  29. Broad KD, Kendrick KM, Sirinathsinghji DJ, Deverne EB. Changes in oxytocin immunoreactivity and mRNA expression in the sheep brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone. J Neuroendocrinol 1993; 5:435–444.[CrossRef][Medline]
  30. Levin MC, Sawchenko PE. Neuropeptide co-expression in the magnocellular neurosecretory system of the female rat: evidence for differential modulation by estrogen. Neuroscience 1993; 54:1001–1018.[CrossRef][Medline]
  31. Koch M, Ehret G. Immunocytochemical localization and quantitation of estrogen-binding cells in the male and female (virgin, pregnant, lactating) mouse brain. Brain Res 1989; 489:101–112.[CrossRef][Medline]
  32. Simerly RB, Chang C, Muramatsu M, Swanson LW. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J Comp Neurol 1990; 294:76–95.[CrossRef][Medline]
  33. Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S. Human estrogen receptor ß binds DNA in a manner similar to and dimerizes with estrogen receptor-{alpha}. J Biol Chem 1997; 272:25832–25838.[Abstract/Free Full Text]
  34. Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M. The complete primary structure of human ER-ß (hERbeta) and its heterodimerization with ER-{alpha} in vivo and in vitro. Biochem Biophys Res Commun 1998; 243:122–126.[CrossRef][Medline]
  35. Petterson K, Grandien K, Kuiper GGJM, Gustafsson J-A. Mouse estrogen receptor ß forms estrogen response element-binding heterodimers with estrogen receptor {alpha}. Mol Endocrinol 1997; 11:1486–1496.[Abstract/Free Full Text]
  36. Paech K, Webb P, Kuiper GGJM, Nilsson S, Gustafsson J-A, Kushner PJ, Scanlan TS. Differential ligand activation of estrogen receptors ER{alpha} and ERß at AP1 sites. Science 1997; 277:1508–1510.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 EndocrinologyHome page
T. R. Chakraborty, L. Ng, and A. C. Gore
Age-Related Changes in Estrogen Receptor {beta} in Rat Hypothalamus: A Quantitative Analysis
Endocrinology, September 1, 2003; 144(9): 4164 - 4171.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
S. L. Hardy, G. M. Anderson, M. Valent, J. M. Connors, and R. L. Goodman
Evidence That Estrogen Receptor Alpha, but Not Beta, Mediates Seasonal Changes in the Response of the Ovine Retrochiasmatic Area to Estradiol
Biol Reprod, March 1, 2003; 68(3): 846 - 852.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. F. Palter, A. B. Tavares, A. Hourvitz, J. D. Veldhuis, and E. Y. Adashi
Are Estrogens of Import to Primate/Human Ovarian Folliculogenesis?
Endocr. Rev., June 1, 2001; 22(3): 389 - 424.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. K. Österlund, J.-A. Gustafsson, E. Keller, and Y. L. Hurd
Estrogen Receptor {beta} (ER{beta}) Messenger Ribonucleic Acid (mRNA) Expression within the Human Forebrain: Distinct Distribution Pattern to ER{alpha} mRNA
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3840 - 3846.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
C. J. Scott, A. J. Tilbrook, D. M. Simmons, J. A. Rawson, S. Chu, P. J. Fuller, N. H. Ing, and I. J. Clarke
The Distribution of Cells Containing Estrogen Receptor-{alpha} (ER{alpha}) and ER{beta} Messenger Ribonucleic Acid in the Preoptic Area and Hypothalamus of the Sheep: Comparison of Males and Females
Endocrinology, August 1, 2000; 141(8): 2951 - 2962.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Stefanovic, B. Adrian, H. T. Jansen, M. N. Lehman, and R. L. Goodman
The Ability of Estradiol to Induce Fos Expression in a Subset of Estrogen Receptor-{alpha}-Containing Neurons in the Preoptic Area of the Ewe Depends on Reproductive Status
Endocrinology, January 1, 2000; 141(1): 190 - 196.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hileman, S. M.
Right arrow Articles by Jackson, G. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hileman, S. M.
Right arrow Articles by Jackson, G. L.
Agricola
Right arrow Articles by Hileman, S. M.
Right arrow Articles by Jackson, G. L.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS