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Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom CB2 4AT; and the Human and Animal Physiology Group, Department of Animal Science, Wageningen Agricultural University (E.M.V.), Wageningen 6709, The Netherlands
Address all correspondence and requests for reprints to: Dr. Allan E. Herbison, Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom CB2 4AT. E-mail: allan.herbison{at}bbsrc.ac.uk
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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and PR immunoreactivity in NE neurons through
the estrous cycle revealed a fluctuating pattern of expression for both
receptors within the NTS. The percentage of A2 neurons expressing PR
immunoreactivity was low on metestrus and diestrus (3–7%), but
increased significantly to approximately 24% on proestrous morning and
remained at intermediate levels until estrus. The pattern of ER
immunoreactivity in A2 neurons was more variable, but a similar
increment from 11% to 40% of NE neurons expressing ER was found
from diestrus to proestrus. Experiments in ovariectomized,
estrogen-treated and estrogen-plus progesterone-treated rats revealed
that PR immunoreactivity in A2 neurons was induced strongly by estrogen
treatment, whereas progesterone had no significant effect. The numbers
of ER-positive NE neurons were not influenced by steroid treatment.
These observations provide direct evidence for PRs in NE neurons of the
brainstem and show that cyclical patterns of gonadal steroid receptor
expression exist in A2, but not A1, neurons through the rat estrous
cycle. The expression of PR in A2 neurons appears to be driven
principally by circulating estrogen concentrations. The fluctuating
levels of ER and PR expression in these brainstem NE neurons may
help generate cyclical patterns of biosynthetic and electrical activity
within reproductive neural networks. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Early studies showing that NE turnover and content within the hypothalamus fluctuated in response to gonadal steroid manipulations (13, 14, 15) indicated that estrogen and progesterone may regulate the activity of NE neurons. Indeed, more recent studies have shown that gonadal steroids can regulate tyrosine hydroxylase as well as immediate early gene expression within the A1 and A2 neurons (16, 17). Together with evidence for immediate early gene induction in A1 and A2 neurons on proestrus (17, 18) and increments in NE release within the preoptic area at a similar time (14, 19), these observations support the hypothesis that the changing gonadal steroid environment alters NE signaling within the GnRH network to modulate the electrical and transcriptional activities of GnRH neurons (5).
The nature of gonadal steroid action on the A1 and A2 neurons of the
rat is currently under investigation. In terms of estrogen, there is
evidence for the presence of ER within a distinct, topographically
organized subpopulation of A1 and A2 neurons (20, 21, 22). The recent
demonstration of ERß within the caudal medulla of the rat brainstem
suggests that ERß may also be expressed in A1 and A2 neurons (23).
Thus, it would appear that estrogen has a direct route through which
may it influence gene expression and possibly the electrical activity
of A1 and A2 neurons. The situation for progesterone is much less
clear. No studies have examined whether progesterone receptors (PRs)
are expressed in the caudal brainstem, and it is not known whether A1
and A2 neurons synthesize PRs.
The first objective of the present series of studies was to examine
whether PRs were expressed in NE neurons of the caudal brainstem. As
gonadal steroid receptor expression within the brain is known to
fluctuate across the estrous cycle (24, 25) and may thus represent a
molecular event involved in the cyclical activity within neural
networks, the second objective of our studies was to examine the
profile of ER and PR expression in A1 and A2 neurons throughout the
cycle. Finally, to assess the influence that estrogen and progesterone
may exert on ER and PR expression in NE neurons, we have also
determined ER and PR immunoreactivity in the NE neurons of
ovariectomized female rats treated with gonadal steroids.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Another group of animals was used to evaluate the effects of estrogen
and progesterone treatment on ER and PR immunoreactivity in
brainstem NE neurons. Virgin female Wistar rats were ovariectomized
under Avertin anesthesia (2% tribromoethanol and 1% amyl alcohol, 1
ml/100 g BW, ip) 7–10 days before steroid treatment. Animals were
given one of three treatments: 1) oil, single injections of vehicle
(100 µl ethyl oleate, sc; Fluka, Buchs, Germany) administered
at 1030 h on each of the 2 days before perfusion (n = 4); 2)
estradiol benzoate (EB; 5 µg in 100 µl ethyl oleate, sc;
Sigma Chemical Co., Poole, UK) administered at 1030 h
on each of the 2 days before perfusion (n = 6); and 3) single
injections of EB administered as in group 2 and an injection of
progesterone (0.5 mg in 100 µl ethyl oleate; Sigma Chemical Co.) administered at 1030 h on the day before perfusion
(n = 7). Previous work with ovariectomized rats in this laboratory
(26, 27) has shown that EB administered in this manner suppresses LH
secretion, and progesterone treatment for 27 h has been shown by
others to decrease PR messenger RNA (mRNA) expression within the
hypothalamus (24). Animals were anesthetized between 1000–1400 h with
Avertin (1.5 ml/100 g BW, ip) and perfused transcardially with
heparinized saline followed by 4% paraformaldehyde in phosphate
buffer, then postfixed for 1–2 h in the same fixative at room
temperature. Brains were cryoprotected by immersion in a 30% sucrose
solution overnight.
Single labeling PR and ER immunocytochemistry
Three sets of coronal brainstem sections (30 µm thick)
containing the NTS and VLM were cut using a freezing microtome. All
sections were subjected to immunocytochemistry following a previously
detailed procedure (21). In brief, after washing in a 40%
methanol-0.05 M Tris-buffered saline (TBS) solution
containing 1% H2O2, one set of free floating
sections underwent immunocytochemistry for the PR. Sections were
incubated in a polyclonal rabbit antibody, directed against the
DNA-binding domain (amino acids 533–547) of the human progesterone
receptor (1:1000; DAKO Corp., Glostrup, Denmark) for
72 h at 4 C. This was followed by biotinylated goat antirabbit Igs
(1:200; Vector Laboratories, Inc., Peterborough,
UK) and the Vectastain Elite conjugate (1:100;
Vector Laboratories, Inc.) for 90 min each at room
temperature.
For ER immunocytochemistry, an additional set of sections was
incubated in a monoclonal mouse antibody directed against the
N-terminal domain of the human ER (ID5; 1:10; gift from G. Delsol,
Toulouse, France; available from DAKO Corp.) for 72 h
at 4 C. This was followed by biotinylated horse antimouse Igs (1:200;
Vector Laboratories, Inc.) and the Vectastain
Elite avidin-peroxidase conjugate (1:00; Vector Laboratories, Inc.) for 90 min each at room temperature. Immunoreactivities
for both PR and ER were visualized using the glucose oxidase
nickel-enhanced 3,3'-diaminobenzidine tetrahydrochloride (DAB)
technique to yield a black reaction product.
Double labeling immunocytochemistry
Sections that had undergone immunocytochemistry for PR or ER
were then processed for double labeling immunocytochemistry by washing
sections in a 40% methanol-TBS solution containing 1%
H2O2 and incubating them in a monoclonal mouse
antityrosine hydroxylase (anti-TH) antibody (1:4000; MAB 318, Chemicon,
Harrow, UK) for 72 h at 4 C. Pilot experiments comparing
dual labeling of sections with the PR antibody and either this TH
antibody or a polyclonal rabbit antiserum raised against
dopamine-ß-hydroxylase demonstrated that the former combination was
superior. The TH antibody incubation was followed by biotinylated horse
antimouse Igs (1:200; Vector) and the streptavidin horseradish
peroxidase complex (SABC 1:200; Amersham, Aylesbury, UK),
each for 90 min at room temperature. TH immunoreactivity was visualized
using DAB alone to yield a brown reaction product. All antibodies were
diluted in TBS containing 0.25% BSA and 0.3% Triton X-100. Vector
Elite and SABC were diluted in TBS alone. Sections were coverslipped
with DPX (BDH, Poole, UK) before analysis on a Leica Corp.
DM-RB microscope at x10–40 objective magnification.
Antibody specificity and control experiments
The production and specificity of the polyclonal rabbit PR
antibody raised against the human PR has been described previously (25, 28, 29). Liquid phase adsorption control experiments were performed by
overnight incubation of the PR antibody at 4 C with a 100 µg/ml
concentration of the PR peptide used as antigen (amino acids 533–547;
Genosys Biotechnologies, Inc., The Woodlands, TX). Sections incubated
with preadsorbed antibody revealed no nuclear immunoreactivity. The
production and specificity of the ID5 and TH antibodies for use in the
rat brainstem have been reported previously (21). Omission of the
primary ER or PR antibody resulted in the absence of nuclear
immunostaining, and in control experiments undertaken using the double
labeling procedure, no cytoplasmic immunoreactivity was detected after
omission of the TH antibody.
Analysis
The analysis of single and double labeled cells was
undertaken in brainstem sections extending from the caudal to the
rostral medulla by an investigator unaware of the experimental groups.
Coronal brainstem sections were subdivided as previously described (21)
on a cytoarchitectural basis into three different rostrocaudal levels:
1) rostral: immediately rostral to the area postrema (AP -13.6 to
-14.2); 2) middle: area containing and immediately caudal to the area
postrema (AP -14.2 to -14.8); and 3) caudal: midway between the area
postrema and the caudal medulla where the dorsal column fasciculae
overlie the beginning of the NTS (AP -14.8 to -15.5), corresponding
to plates 68–69, 70–71, and 72–73, respectively, of Swanson (30) and
represented in Fig. 1
. In each rat and
for all analyses, cell profile counts were obtained from a minimum of
six sections at each of the three levels. In the case of the NTS, all
immunoreactive cells within its boundaries were counted bilaterally,
whereas analysis of the VLM was undertaken on a hemisection basis to
ensure the correct rostrocaudal grouping of cells. In double labeled
sections all nickel- and DAB-stained nuclear profiles, brown
DAB-stained cytoplasmic profiles with nuclear exclusions, and double
labeled cells exhibiting black nuclei and a brown cytoplasm were
counted. Individual values from animals were combined to provide the
mean at each level, and these were used to determine the group
mean ± SEM in all cases. In cycling animals, we were
interested in defining differences between temporally contiguous groups
and accordingly performed sequential Mann-Whitney tests. In the gonadal
steroid treatment experiments, multiple cross-comparisons were made,
and statistical analysis was performed using ANOVA followed by
post-hoc Student-Newman-Keuls tests.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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) as
described previously (21, 31). No significant changes in the number of
TH neurons were detected in either the NTS or the VLM through the
estrous cycle (Tables 1 and 2). As reported previously (21), the
maximum number of TH-immunoreactive cells found were in the middle
division of the NTS, although substantial numbers were also seen in the
rostral and caudal sections (Tables 1 and 2). Numerous
TH-immunoreactive cells were also detected within the VLM, although no
rostro-caudal differences in their distribution were evident (Tables 1 and 2).
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and Fig. 1).
Cells exhibiting PR immunoreactivity were also found at much lower
density within the area postrema, the caudal aspect of the spinal
nucleus of the trigeminal nerve, and along the ventral aspect of the
brainstem (Fig. 1). Compared with the NTS, very few PR-immunoreactive
cells were detected in the VLM (Table 1). The number of
PR-immunoreactive cells encountered in the middle and caudal sections
of the NTS changed significantly during the estrous cycle, when an
increase was found from the lowest level of expression on the afternoon
of diestrus to maximal expression on the morning of proestrus
(P < 0.05) in both middle and caudal divisions of the
NTS (Table 1). The very low numbers of PR-immunoreactive cells detected
in the VLM precluded any similar statistical analysis.
PR immunoreactivity in A1 and A2 norepinephrine neurons
through the estrous cycle
The great majority of double labeled cells displaying brown
cytoplasmic staining for TH and black nuclear staining for PR (Fig. 2) were found within the middle and
caudal levels of the NTS (Table 1 and Figs. 1 and 3). Very few (less than one cell per
section) double labeled A2 neurons were found in the more rostral
sections (Table 1), whereas A1 neurons displaying PR immunoreactivity
were rare and were only detected in the most caudal sections (Table 1).
Neurons staining for TH accounted for 30–50% of all PR-immunoreactive
cells identified in the NTS (Table 1).
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and Table 1). The number (Table 1) and percentage (Fig. 3) of middle
division A2 neurons with PR immunoreactivity was lowest (0.6
cells/section or 3% of all A2 cells) on diestrous morning, but rose
significantly (P < 0.05) on proestrous morning (6.3
cells/section, or 24%) to reach a peak before declining on proestrous
afternoon (4 cells/section, or 14%; Fig. 3). A similar temporal
pattern was seen in the caudal region (Fig. 3), with a significant
(P < 0.05) increase in the percentage of A2 cells
exhibiting PR staining occurring from the afternoon of diestrus (1%)
to proestrous morning (21%). At this rostrocaudal level, PR
immunoreactivity in A2 cells remained at an intermediate level of
around 10% even during metestrous and diestrous morning (Fig. 3). The
same trend was apparent in the rostral division of the A2 (Fig. 3), but
very few double labeled cells were encountered at this level.
ER immunoreactivity in A1 and A2 norepinephrine
neurons through the estrous cycle
The distribution of ER immunoreactivity within the caudal
medulla was the same as that reported previously (21). Compared to PR
staining, the numbers of ER-immunoreactive cells encountered per
section in the NTS were greater at essentially all levels examined
(Table 2), and additional populations of ER-immunoreactive cells
were identified throughout the VLM, in the reticular nuclei, and within
the lateral boundaries of the caudal spinal nucleus of the trigeminal
nerve. Again, as reported previously (21), a clear rostro-caudal
topography existed in terms of ER immunoreactivity within the A1 and
A2 neurons, with the highest density of ER-expressing NE neurons
being detected in the caudal level of the NTS and VLM (Table 2).
Temporal changes in ER immunoreactivity also occurred during the
estrous cycle (Table 2). Despite a substantial degree of variability
between animals, a significant increase in the number of
ER-expressing neurons was encountered between diestrous afternoon
and proestrous morning within the caudal NTS (P <
0.05; Table 2). This change was also reflected in a significant
increase (P < 0.05) in the numbers (Table 2) and
percentage (Fig. 3) of A1 and A2 neurons found to express ER
immunoreactivity between these 2 days in the caudal and middle
divisions of the NTS. However, as with the total number of
ER-immunoreactive cells encountered, the number of double labeled
cells also varied markedly between animals and resulted in relatively
high levels of ER expression in A2 neurons that did not change
significantly across the cycle at other times (Fig. 3). We found no
evidence for changing patterns of ER immunoreactivity within A1
neurons during the estrous cycle (Table 2).
PR and ER immunoreactivity in the brainstem in response to
gonadal steroid manipulation
The distribution of PR, ER, and TH immunoreactivity within the
caudal medulla of ovariectomized control and gonadal steroid-treated
rats was exactly the same as that described above for intact animals.
The numbers of TH-immunoreactive cells detected at the three different
levels in the NTS and VLM were not different in the three treatment
groups. The total number of PR-immunoreactive cells detected in the
caudal level of the NTS was increased after the administration of
estrogen to ovariectomized rats (P < 0.05), whereas
the number of ER-immunoreactive cells did not change (Table 3). No differences in the number of PR-
or ER-immunoreactive cells were detected after progesterone
administration to estrogen-treated ovariectomized rats. The numbers of
ER- and PR-expressing neurons in the VLM did not change in response
to either of the gonadal steroid manipulations (Table 3).
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) and percentage (Fig. 4) of dual labeled A2 neurons in
estrogen-treated ovariectomized rats revealed a strong induction of PR
immunoreactivity in NE neurons of the middle and caudal NTS after
estrogen treatment. For example, in the caudal NTS, the number of A2
neurons with PR staining increased from approximately 2 to nearly 10
cells/section (Table 3), and this represented an increase from 10% of
all A2 neurons in ovariectomized rats to proestrus-like levels of
around 30% of all A2 cells after estrogen treatment (Fig. 4). No
changes were detected in the low numbers of PR-expressing A1 neurons
(Table 3). Progesterone treatment had no effect on the number of
PR-immunoreactive A1 or A2 neurons (Fig. 4 and Table 3).
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) and percentage (Fig. 4) of NTS and VLM neurons
found to express ER immunoreactivity were not influenced by gonadal
steroid treatment. |
Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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One surprising aspect of the distribution of PR-immunoreactive cells
within the caudal brainstem has been the relative scarcity of labeled
cells within the VLM and, specifically, the A1 neurons. This
observation was made in all animals regardless of their endocrine state
and suggests that little PR is synthesized by A1 neurons at any time of
the estrous cycle. This is noteworthy, as ER-expressing A1 neurons
are plentiful, especially in the most caudal brainstem (21). Together,
this would suggest that the A1 neurons may be a further example of a
small group of neurons that expresses ERs but not PRs (35, 36). In
contrast, the PR expression by A2 neurons paralleled that of ER
immunoreactivity, with a clear rostrocaudal topography in gonadal
steroid receptor expression within the brainstem. Thus, very few A2
neurons located in the rostral part of the NTS express ERs or PRs,
whereas approximately 40% and 20% of A2 neurons in the caudal medulla
contain ER and PR immunoreactivity, respectively.
In terms of the ER- and PR-expressing cell populations of the NTS,
our studies indicate that at least 50% are not synthesizing dopamine
or NE. Relatively little is known about the neurochemical identity of
these other steroid-receptive cells, but preliminary work (Simonian,
S. X., and A. E. Herbison, unpublished observations) shows
that up to 20% of ER-expressing neurons in the NTS contain the
neuropeptide somatostatin. Furthermore, there appears to be a high
degree of neurochemical organization in the projections of
ER-expressing NTS neurons; whereas 90% of ER-containing neurons
projecting to the rostral preoptic area synthesize NE (4), none of the
ER-containing neurons projecting to the supraoptic nucleus contain NE
(37).
Although we have not proven that A2 neurons express both ER and PR
receptors, we note that the number of NE neurons with PRs was
approximately half the number found to express ER at each level of
the NTS in cycling rats. This along with evidence for the induction of
PRs exclusively in cells with ERs (35, 36) suggest that up to half of
estrogen-receptive A2 neurons synthesize PRs. Interestingly, the one
exception to this situation was after estrogen treatment of
ovariectomized rats, when approximately 20% of "middle" A2 neurons
expressed PR, whereas only 10% were found to be immunoreactive for
ER. Whether the remaining 10% of PR-expressing A2 neurons contain
ERß is not known. If these A2 neurons were found to possess neither
ER, they would represent an interesting case of ER-independent
activation of PR expression by estrogen.
The ability of estrogen to directly up-regulate PR gene expression
within the hypothalamus is well established (33, 35, 36), although it
remains undecided whether this involves ER, ERß, or both of these
transcription factors (38, 39). Our present results demonstrate that
estrogen also induces PR expression within the A2 neurons of the
brainstem and indicate that estrogen is likely to underlie the
induction of PR immunoreactivity in these cells on proestrous morning.
It is noteworthy that we have identified a rather abrupt increase in PR
expression within A2 neurons on proestrous morning despite the fact
that estrogen concentrations rise gradually throughout diestrus and
proestrus. One explanation for the abrupt increase in PR may be that a
threshold level of estrogen is required to activate PR gene
transcription and/or that a delay may exist in the translation of PR
transcripts in A2 neurons. Alternatively, it may be that an inhibitory
influence of postovulatory progesterone secretion counterbalances the
stimulatory effect of rising estrogen levels in diestrus. Against this
latter hypothesis, however, is our evidence that 24–27 h of
progesterone treatment upon an estrogen background did not alter PR
immunoreactivity in A2 neurons. Further work will be required to
examine this issue.
Somewhat surprisingly, we found little direct evidence for the gonadal
steroid regulation of ER immunoreactivity in brainstem NE neurons.
Previous studies within the hypothalamus have shown that ER mRNA
expression is down-regulated by estrogen (24, 40), whereas we detected
no changes in ER immunoreactivity within either A1 or A2 neurons after
estrogen administration to ovariectomized rats. Furthermore, we found a
significant increase, rather than a decrease, in the number
ER-expressing A1 and A2 neurons on proestrous morning when
circulating estrogen concentrations are rising. There is good evidence
for the region-specific regulation of ER gene expression in the brain
(41), and it would appear that the regulation of ER within brainstem
NE neurons may be distinct from that occurring within hypothalamic
cells.
A number of studies have shown that the biosynthetic and electrical
activities of brainstem NE neurons are influenced by gonadal steroids.
Thus, estrogen has been demonstrated to increase immediate early gene
expression in A2 neurons (17) as well as the spontaneous firing rate of
A1 neurons (42), and this may underlie the elevated NE turnover in the
hypothalamus after estrogen treatment (13, 14, 15). It has been suggested
that estrogen acts principally through the A2 neurons to enhance the
diurnal variation in NE release within the hypothalamus (4). Although
we encountered substantial interanimal variability in the pattern of
ER expression within A1 and A2 neurons, it is of note that the
lowest levels of ER expression by A2 neurons were in the two groups
of animals killed in the afternoon. This observation raises the
intriguing possibility that a pattern of steroid-independent, diurnal
ER expression occurs in brainstem NE neurons.
Much less data are available in terms of progesterone’s influence on brainstem NE neurons. The release of NE in the ventromedial nucleus (43) and median eminence (15) is elevated by acute progesterone treatment, whereas progesterone exposure for 24 h is thought to antagonize estrogen’s stimulatory actions on NE release throughout the hypothalamus (44). Our observation here of PRs expressed predominantly within A2 rather than A1 neurons indicates that any direct genomic influences of progesterone on NE signaling within the hypothalamus arise from these NTS neurons. The induction of PRs in A2 neurons on proestrous morning would enable the rising progesterone levels later that day to alter gene expression and, thus, the behavior of the subpopulation of A2 neurons with PRs. However, the complete absence of data on the molecular effects of progesterone on NE neurons makes it impossible to determine whether direct genomic actions of progesterone in A2 neurons may be responsible for acutely enhancing and/or chronically repressing their activity.
The gonadal steroid-dependent changes in brainstem NE neurons are
likely to have a permissive role in the regulation of GnRH secretion
and biosynthesis (5). Retrograde labeling experiments from the rostral
preoptic area have highlighted the importance of the A1 and A2 neurons
with respect to the cell bodies of the GnRH neurons (8), and triple
labeling studies have gone on to show that it is exclusively the A2
neuronal afferents that express ER (45). The finding here that PRs
are only found to any substantial degree in A2 neurons highlights
further the potential importance of these cells in gonadal steroid
signaling to the GnRH neurons. We also have preliminary evidence that
PR-expressing A2 neurons project to the vicinity of the GnRH cell
bodies in the rostral preoptic area (Haywood, S. A., et
al., unpublished observations). Thus, evidence exists for both ER-
and PR-expressing A2 neurons that project to the vicinity of the GnRH
neurons as well as for the induction of both ovarian steroid receptors
in A2 neurons on the morning of proestrus. These observations further
support the hypothesis that the rising titers of estrogen during the
cycle may modulate NE transmission directed at the GnRH neurons to
facilitate the increase in GnRH biosynthesis and secretion that occurs
at this time (5). Equally, the induction of PR expression within these
neurons in early proestrus may occur in readiness for the rise in
progesterone concentrations later that day and/or be involved in the
ligand-independent activation of gene expression (46) in A2 neurons. In
this sense, subpopulations of A2 cells may provide a neural substrate
within the GnRH network where coordinated PR- and ER-regulated gene
expression occurs.
In summary, we show here that many NE neurons in the NTS express PRs
and that the pattern of PR immunoreactivity in these neurons fluctuates
through the estrous cycle; a marked, and probably estrogen-dependent,
induction of PR expression was found to occur on proestrous morning.
The expression of ER immunoreactivity in A2 neurons was also found
to increase significantly on proestrous morning, although little
evidence was found for gonadal steroid regulation of ER expression
within brainstem NE neurons. These changes in gonadal steroid receptor
expression within the A2 neurons, in particular, may represent
molecular events that underlie the ability of estrogen and progesterone
to alter NE transmission within the hypothalamus and elsewhere in the
brain.
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Acknowledgments |
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Footnotes |
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Received December 16, 1998.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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and -ß mRNA in the
rat central nervous system. J Comp Neurol 388:507–525[CrossRef][Medline]
gene disrupted mice. Proc Natl Acad Sci USA 94:11008–11012 gene disrupted mice. J Neurosci 18:9556–9563-containing neurons projecting to the
vicinity of the GnRH perikarya in the rostral preoptic area of the rat.
J Comp Neurol, in press
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A. M. Cason, M. DenBleyker, K. Ferrence, J. C. Smith, and T. A. Houpt Sex and estrous cycle differences in the behavioral effects of high-strength static magnetic fields: role of ovarian steroids Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R659 - R667. [Abstract] [Full Text] [PDF]
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C. V. V. Helena, M. de Oliveira Poletini, G. L. Sanvitto, S. Hayashi, C. R. Franci, and J. A. Anselmo-Franci Changes in {alpha}-estradiol receptor and progesterone receptor expression in the locus coeruleus and preoptic area throughout the rat estrous cycle J. Endocrinol., February 1, 2006; 188(2): 155 - 165. [Abstract] [Full Text] [PDF]
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H. L. Rincavage, D. P. McDonnell, and C. M. Kuhn Expression of Functional Estrogen Receptor {beta} in Locus Coeruleus-Derived Cath.a Cells Endocrinology, July 1, 2003; 144(7): 2829 - 2835. [Abstract] [Full Text] [PDF]
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S. Temel, W. Lin, S. Lakhlani, and L. Jennes Expression of Estrogen Receptor-{alpha} and cFos in Norepinephrine and Epinephrine Neurons of Young and Middle-Aged Rats during the Steroid-Induced Luteinizing Hormone Surge Endocrinology, October 1, 2002; 143(10): 3974 - 3983. [Abstract] [Full Text] [PDF]
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T. A. Richter, D. S. Spackman, J. E. Robinson, S. Dye, T. G. Harris, D. C. Skinner, and N. P. Evans Role of Endogenous Opioid Peptides in Mediating Progesterone-Induced Disruption of the Activation and Transmission Stages of the GnRH Surge Induction Process Endocrinology, December 1, 2001; 142(12): 5212 - 5219. [Abstract] [Full Text] [PDF]
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N. Geary, L. Asarian, K. S. Korach, D. W. Pfaff, and S. Ogawa Deficits in E2-Dependent Control of Feeding, Weight Gain, and Cholecystokinin Satiation in ER-{alpha} Null Mice Endocrinology, November 1, 2001; 142(11): 4751 - 4757. [Abstract] [Full Text] [PDF]
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N. Geary and L. Asarian Estradiol increases glucagon's satiating potency in ovariectomized rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2001; 281(4): R1290 - R1294. [Abstract] [Full Text] [PDF]
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L. A. Eckel and N. Geary Estradiol treatment increases feeding-induced c-Fos expression in the brains of ovariectomized rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2001; 281(3): R738 - R746. [Abstract] [Full Text] [PDF]
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H. Sakamoto, K. Ukena, and K. Tsutsui Effects of Progesterone Synthesized De Novo in the Developing Purkinje Cell on Its Dendritic Growth and Synaptogenesis J. Neurosci., August 15, 2001; 21(16): 6221 - 6232. [Abstract] [Full Text] [PDF]
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