| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Articles |
Division of Genetics (U.B.K., W.W.C.), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Department of Obstetrics, Gynecology, and Reproductive Sciences (A.J., A.S.), University of Texas Medical School, Houston, Texas 77030
Address all correspondence and requests for reprints to: Ursula B. Kaiser, G. W. Thorn Research Building, Room 909, Brigham and Women’s Hospital, 20 Shattuck Street, Boston, Massachusetts 02115. E-mail: kaiser{at}rascal.med.harvard.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, LHß, and FSHß subunit genes
in vivo. We demonstrate differential effects of varying
GnRH pulse frequency in vitro in superfused primary
monolayer cultures of rat pituitary cells. Cells were treated with 10
nM GnRH pulses for 24 h at a frequency of every 0.5,
1, 2, or 4 h. , LHß, and FSHß messenger RNA (mRNA) levels
were increased by GnRH at all pulse frequencies. and LHß mRNA
levels and LH secretion were stimulated to the greatest extent at a
GnRH pulse frequency of every 30 min, whereas FSHß mRNA levels and
FSH secretion were stimulated maximally at a lower GnRH pulse
frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were
increased by GnRH at all pulse frequencies and were stimulated
maximally at a GnRH pulse frequency of every 30 min. Similar results
were obtained when the dose of each pulse of GnRH was adjusted to
maintain a constant total cumulative dose of GnRH over 24 h. These
data show that gonadotropin subunit gene expression is regulated
differentially by varying GnRH pulse frequencies in
vitro, suggesting that the differential effects of varying GnRH
pulse frequencies on gonadotropin subunit gene expression occur
directly at the level of the pituitary. The pattern of regulation of
GnRHR mRNA levels correlated with that of and LHß but was
different from that of FSHß. This suggests that and LHß mRNA
levels are maximally stimulated when GnRHR levels are relatively high,
whereas FSHß mRNA levels are maximally stimulated at lower levels of
GnRHR expression, and that the mechanism for differential regulation of
the gonadotropins by varying pulse frequencies of GnRH may involve
levels of GnRHR. Furthermore, these data suggest that the mechanisms
whereby varying GnRH pulse frequencies stimulate , LHß, and GnRHR
gene expression are similar, whereas the stimulation of FSHß mRNA
levels may be different. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
GnRH stimulates the secretion of LH and FSH, as well as the
biosynthesis of the gonadotropin subunits, , LHß, and FSHß. The
stimulation of gonadotropin biosynthesis and secretion by GnRH is
dependent on the pulsatile nature of GnRH delivery to the anterior
pituitary. Administration of exogenous GnRH in a continuous fashion
results in the down-regulation of gonadotropin subunit messenger RNA
(mRNA) levels and of LH and FSH secretion, whereas pulsatile GnRH
stimulates mRNA levels and secretion (3, 4, 5, 6). This variability in GnRH
responsiveness seems to correlate, at least partially, with the
concentration of GnRH receptor (GnRHR) on the cell surface (7, 8).
The frequency and amplitude of GnRH pulses secreted by the
hypothalamus vary under different physiological conditions (9). It has
been postulated that the frequency and amplitude of GnRH stimulation
provide signals for the differential regulation of LH and FSH secretion
(10). At higher GnRH pulse frequencies, LH secretion increases
disproportionately more than FSH secretion, whereas, at lower GnRH
pulse frequencies, FSH secretion is favored (11, 12). In recent years,
several investigators have provided further support for this hypothesis
using in vivo models by showing that the frequency and
amplitude of GnRH pulses also determine , LHß, and FSHß mRNA
levels (13, 14, 15, 16). This regulation seems to occur at the level of gene
transcription (17, 18).
Although the data from most in vivo studies provide evidence in support of frequency-dependent gonadotropin regulation by GnRH, the concept is not supported by other studies (19), and the mechanism of such regulation is not clear. Many of the in vivo models have relied on orchidectomized male rats treated with testosterone to suppress endogenous GnRH release. Testosterone, as well as other steroids and other endogenous factors, may modulate GnRH actions. Indeed, studies in ovariectomized female rats treated with phenoxybenzamine to suppress endogenous GnRH secretion have not produced the same results (20). It also has been suggested that the presence of testosterone is necessary for stimulation of LHß mRNA levels by pulsatile GnRH (21).
To provide direct evidence of differential regulation of gonadotropin subunit gene expression and gonadotropin secretion by varying GnRH pulse frequencies at the level of pituitary cells, we have used an in vitro model of superfused primary rat pituitary cultures. This model allows for controlled conditions, thereby eliminating the possible effects of neuroendocrine, gonadal, or other extrapituitary factors. We have previously demonstrated the suitability of this system for such studies by showing that superfused pituitary cells maintain prolonged secretory responsiveness to GnRH pulses and that all gonadotropin subunit mRNAs could be upregulated under these conditions (22).
In addition, to investigate whether frequency-dependent regulation of LH and FSH secretion could involve regulation of GnRHR synthesis, we have included determinations of GnRHR gene expression in our study. It has been shown previously that GnRH binding and GnRHR mRNA levels depend on the pattern of GnRH delivery (23, 24). Furthermore, GnRHR mRNA levels are regulated by gonadectomy and sex steroid hormone replacement, through the estrous cycle, and by pulsatile GnRH in vivo (24, 25, 26). In this report, we demonstrate the correlation between GnRHR and gonadotropin subunit gene expression in response to varying GnRH pulse frequencies, suggesting a possible mechanism for these differential effects of GnRH.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Preparation of RNA
Total RNA was prepared from cultured cells by the acid
guanidinium thiocyanate-phenol-chloroform procedure (28) using RNAzol B
(Biotecx Laboratories, Inc., Houston, TX). The RNA concentrations were
estimated by measuring the A260.
mRNA determinations
Five micrograms of total RNA (A260) from each sample
were denatured and subjected to electrophoresis and diffusion blotting
onto a Duralon membrane (Stratagene, La Jolla, CA) (29). Each blot was
sequentially hybridized with rat -subunit, LHß, FSHß, GnRHR, and
cyclophilin cDNA probes (30). Blots were washed and subjected to
phosphorimager analysis (Molecular Dynamics, Sunnyvale, CA), and band
densities were quantitated. The amount of total RNA in each sample was
internally standardized within each blot by correcting the gonadotropin
subunit and GnRHR mRNA levels according to the levels of cyclophilin
mRNA.
RIA of LH and FSH
Media samples were collected at 6-min intervals during the final
4 h of superfusion for LH and FSH RIAs. The LH and FSH contents
were determined as previously described (27). Specific RIAs were
performed according to the procedure recommended by the NIH. The
results are expressed in terms of LH and FSH RP-2 standards. The intra-
and interassay variations were 8% and 9% for LH and 7% and 9% for
FSH, respectively. Total LH and FSH secretion over the 4-h time period
of collection was then determined and compared with secretion in
control cells not treated with GnRH.
Statistical analysis
Each experiment was repeated at least 4 times. Cumulative data
from individual experiments were combined, with the mRNA levels at a
GnRH pulse frequency of every 1 h used as a standard for
comparison between experiments. Results are expressed as the mean
± SEM. Data were analyzed by one-way ANOVA followed by
post hoc comparisons with Fisher’s protected least
significant-difference test. In all cases, differences were considered
significant if P < 0.05. The errors in the ratios were
calculated by standard methods of propagation of errors in computation
(31).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, LHß,
and FSHß subunit mRNA levels, corrected for cyclophilin mRNA levels,
are shown for each frequency of pulsatile GnRH tested (Fig. 1
). Values are the combined results of four independent
experiments expressed as a percentage relative to levels at an hourly
GnRH pulse frequency. Pulsatile GnRH significantly stimulated ,
LHß, and FSHß subunit mRNA levels at all pulse frequencies tested.
LHß subunit mRNA levels were stimulated to the greatest extent at a
GnRH pulse frequency of every 30 min. At lower frequencies, levels also
were increased but to a lesser extent. In contrast, FSHß subunit mRNA
levels were stimulated to the greatest extent at lower GnRH pulse
frequencies, such as every 2 h. subunit mRNA levels were less
dependent on GnRH pulse frequency, but seem to follow a pattern similar
to that of LHß; that is, they were stimulated to the greatest extent
at GnRH pulse frequencies of every 30 min. The responses of all three
(, LHß, and FSHß) mRNA levels to GnRH pulses every 2 h are
significantly different from those in response to pulses every 30 min
(LHß - GnRH every 30 min: 116.2 ± 8.6% vs. GnRH
every 2 h: 68.8 ± 8.7%, P < 0.0005; FSHß
- GnRH every 30 min: 80.5 ± 4.5% vs. GnRH every
2 h: 101.8 ± 3.1%, P < 0.005; - GnRH
every 30 min: 114.8 ± 4.9% vs. GnRH every 2 h:
98.2 ± 5.4%, P < 0.01).
|
).
Like and LHß, GnRHR mRNA levels were increased to the greatest
extent at a GnRH pulse frequency of every 30 min; at a GnRH pulse
frequency of every 2 h, GnRHR mRNA levels were increased to a
significantly lesser degree (GnRH every 30 min: 101.8 ± 9.7%
vs. GnRH every 2 h: 74.2 ± 5.2%,
P < 0.05).
|
). LH secretion was stimulated to the greatest extent
at a GnRH pulse frequency of every 30–60 min, whereas FSH secretion
was stimulated to the greatest extent at a GnRH pulse frequency of
every 1–2 h. LH and FSH secretion were significantly different at a
GnRH pulse frequency of every 2 h, compared with every 30 min (LH
- GnRH every 30 min: 621 ± 107% vs. GnRH every 2
h: 394 ± 65%, P < 0.005; FSH - GnRH every 30
min: 217 ± 52% vs. GnRH every 2 h: 412 ±
51%, P < 0.0005). As a result, the ratio of LH:FSH
secreted was 3.0 ± 0.6 at a GnRH pulse frequency of every 30 min
but only 0.9 ± 0.2 at a pulse frequency of every 2 h.
|
). That is, pulsatile GnRH again
significantly stimulated , LHß, and FSHß subunit mRNA levels at
all pulse frequencies and concentrations tested. and LHß subunit
mRNA levels were stimulated to the greatest extent at a GnRH pulse
concentration of 5 nM and frequency of every 30 min,
whereas FSHß subunit mRNA levels were stimulated to the greatest
extent at a GnRH pulse concentration of 20 nM and frequency
of every 2 h (LHß - GnRH every 30 min: 109.8 ± 8.5%
vs. GnRH every 2 h: 65.3 ± 18.2%,
P < 0.005; FSHß - GnRH every 30 min: 79.0 ±
6.1% vs. GnRH every 2 h: 108.3 ± 8.5%,
P < 0.005; - GnRH every 30 min: 107.2 ±
7.2% vs. GnRH every 2 h: 83.3 ± 13.3%,
P < 0.05). LH and FSH secretion was again stimulated
by pulsatile GnRH at all pulse frequencies and amplitudes tested, with
similar results to those observed when a fixed GnRH concentration was
used (data not shown).
|
). GnRHR mRNA levels were increased to the greatest
extent at a GnRH pulse concentration of 5 nM and a
frequency of every 30 min; at a GnRH pulse concentration of 20
nM and frequency of every 2 h, GnRHR mRNA levels were
increased to a significantly lesser degree (GnRH every 30 min:
105.7 ± 8.4% vs. GnRH every 2 h: 78.3 ±
17.5%, P < 0.005).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and FSHß mRNA levels were increased (5, 33). In our experimental
paradigm, , LHß, and FSHß subunit mRNA levels were increased
significantly by GnRH at all pulse frequencies tested. This is
consistent with our previous report of the stimulation of , FSHß,
and LHß mRNA by pulsatile GnRH. subunit mRNA levels were
stimulated after 10 and 20 h of pulsatile GnRH, FSHß mRNA levels
were stimulated after 4, 10, and 20 h of pulsatile GnRH, whereas
LHß mRNA levels were increased only after 20 h of pulsatile GnRH
treatment (22). The differences between our studies and previous
in vitro studies may be caused by the different durations of
exposure to pulsatile GnRH. Many of the in vivo studies that
showed an increase in LHß mRNA levels by pulsatile GnRH were
performed using 48 h of pulsatile GnRH treatment (13, 34), and the
maximal stimulation of LHß gene transcription by pulsatile GnRH
in vivo was shown to be after 24 h (18). Alternatively,
the difference may be caused by the use of male rats in our studies but
female rats in other studies (5). Pulsatile GnRH has been shown to
increase LHß subunit mRNA levels in vivo in male rats, but
not in females, unless the females are exposed to testosterone (20, 21, 34, 35).
In this study, GnRH pulse frequency differentially affected the
magnitude of the stimulatory response of the gonadotropin subunit mRNA
levels to GnRH. Focusing on the GnRH pulse intervals of 30
vs. 120 min (which are the intervals at which the greatest
differences were observed in vivo), LHß subunit mRNA
levels were stimulated to a greater extent by a GnRH pulse frequency of
every 30 min. In contrast, FSHß subunit mRNA levels were stimulated
to a greater extent by the lower GnRH pulse frequency, every 120 min.
This was true both with a fixed concentration of 10 nM GnRH
per pulse and with an adjusted GnRH concentration per pulse, so that
the total cumulative GnRH administered over 24 h was constant.
subunit mRNA levels were less stringently regulated by GnRH pulse
frequency but also were greater at a GnRH pulse frequency of every 30
min. These data are consistent with observations in vivo
(13, 15, 16, 34, 35). Thus, gonadotropin subunit gene expression is
regulated differentially by varying GnRH pulse frequencies in
vitro in a parallel fashion to that observed in vivo.
This suggests that the differential effects of varying GnRH pulse
frequencies on gonadotropin subunit gene expression occur directly at
the level of the pituitary, not involving extrapituitary steroid or
neuroendocrine factors. We have not, however, excluded the possibility
of an indirect effect involving other nongonadotrope pituitary cell
types.
Our data differ somewhat from those of another study, which failed to show that slow frequency GnRH pulses preferentially increased FSHß mRNA levels or FSH secretion in vitro (33). However, it compared a GnRH pulse frequency of every h with every 4 h. In fact, our data are consistent with theirs, as we saw a maximal stimulation of FSHß mRNA levels and FSH secretion at a GnRH pulse frequency of every 2 h; the stimulation of FSHß mRNA levels and FSH secretion when GnRH was delivered at 4 h intervals was significantly lower, even when the cumulative GnRH dose was controlled.
LH and FSH secretion were stimulated differentially by varying GnRH pulse frequencies, paralleling the changes observed in LHß and FSHß mRNA levels. LH secretion was maximally stimulated at a GnRH pulse frequency of every 30 min, whereas FSH secretion was maximally stimulated when the cells were treated with pulsatile GnRH every 2 h. Thus, gonadotropin subunit gene expression and LH and FSH secretion seem to be coordinately regulated in vitro. Moreover, the pattern of regulation of secretion mirrors that observed in vivo, confirming that our in vitro model of superfused primary rat pituitary cell cultures reflects the in vivo physiological situation (11, 12).
Like LHß, GnRHR mRNA levels were stimulated to the greatest extent by a GnRH pulse frequency of every 30 min. Thus, GnRHR mRNA levels are regulated differentially by varying GnRH pulse frequencies, with the pattern of regulation correlating with that of LHß mRNA but different from that of FSHß. This suggests that LHß mRNA levels are maximally stimulated when GnRHR concentrations are relatively high, whereas FSHß mRNA levels are maximally stimulated at lower concentrations of GnRHR. These data are consistent with observations in vivo that GnRH pulse frequency determines the number of pituitary GnRHR, as determined by GnRH binding studies, with maximal receptor numbers occurring after 30-min pulses for 48 h (23), although studies of GnRHR mRNA levels in vivo did not show a significant difference between GnRHR mRNA levels after 12 h of pulsatile GnRH given at 30-min vs. 2-h intervals (26). It may be necessary to expose the animals to the pulsatile GnRH paradigms for longer times, such as 24 or 48 h, to elicit a significant difference. Thus, it seems that GnRHR mRNA levels and receptor number are regulated in a coordinate fashion both in vivo and in vitro.
These data suggest that the mechanisms whereby varying GnRH pulse
frequencies stimulate LHß and GnRHR gene expression are similar,
whereas the mechanism of stimulation of FSHß gene expression may be
different. We hypothesize that when GnRH is released from the
hypothalamus at a pulse frequency of every 30 min, expression of the
, LHß, and GnRHR genes are stimulated to a relatively greater
extent compared with lower GnRH pulse frequencies. This results in
gonadotropes expressing relatively high numbers of GnRHR, hence being
more responsive to GnRH. When GnRH is released from the hypothalamus at
a lower pulse frequency, such as every 2 h, expression of the ,
LHß, and GnRHR genes is stimulated to a lesser degree. In contrast,
expression of the FSHß subunit gene is relatively more stimulated.
These responses result in gonadotropes that express lower numbers of
GnRHR and are less responsive to GnRH, yet have higher levels of FSHß
mRNA. These data support our hypothesis that varying GnRH pulse
frequencies regulate differentially LH and FSH subunit gene expression
by regulating pituitary GnRHR concentrations. Using a heterologous
pituitary cell line, GH3 cells, we have shown previously
that different cell surface densities of GnRHR result in the
differential regulation of LH and FSH subunit gene expression by GnRH.
The expression of the and LHß subunit genes is optimally
stimulated at relatively high cell surface densities of GnRHR, whereas
FSHß gene expression is optimally stimulated at lower cell surface
concentrations of the receptor (36).
These data add to the accumulating evidence that there are disparate mechanisms for the regulation of LHß and FSHß subunit gene expression and hence, by inference, for LH and FSH biosynthesis. In addition to the mounting evidence for differential regulation of these genes by GnRH, there is now evidence that the nuclear transcription factor, steroidogenic factor 1, is important for expression of the LHß subunit gene, whereas a role for this factor in FSHß subunit gene expression has not yet been shown (37, 38, 39, 40). Furthermore, a recent report indicates that mice lacking the zinc finger transcription factor, NGFI-A, do not express the LHß subunit gene, whereas FSHß subunit gene expression is preserved (41). Thus, there is evidence that there may be different factors involved in basal, as well as hormonally regulated, expression of the gonadotropin subunit genes.
In summary, , LHß, and FSHß subunit mRNA levels were
increased significantly by GnRH at all pulse frequencies tested in
superfused primary rat anterior pituitary cell cultures. LHß subunit
mRNA levels were stimulated to the greatest extent by a GnRH pulse
frequency of every 30 min, whereas FSHß subunit mRNA levels were
stimulated to the greatest extent by a lower GnRH pulse frequency,
every 2 h. This was true both with a fixed concentration of 10
nM GnRH per pulse and with an adjusted GnRH concentration
per pulse, so that the total cumulative GnRH administered over 24
h was constant. subunit mRNA levels, although less stringently
regulated by GnRH pulse frequency, were maximally stimulated by a GnRH
pulse frequency of every 30 min. Like and LHß, GnRHR mRNA levels
were stimulated to the greatest extent by a GnRH pulse frequency of
every 30 min. These data indicate that gonadotropin subunit gene
expression is regulated differentially by varying GnRH pulse
frequencies in vitro in a similar fashion to that observed
in vivo, which suggests that the mechanism for this
differential regulation occurs directly at the level of the pituitary
gland. The pattern of regulation of GnRHR mRNA correlates with that of
LHß mRNA but is different from that of FSHß. This suggests that
LHß mRNA levels are maximally stimulated when GnRHR concentrations
are relatively high, whereas FSHß mRNA levels are maximally
stimulated at lower concentrations of GnRHR.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 A. Jakubowiak and U. B. Kaiser contributed equally to this work,
and both should be considered first authors.
3 Present affiliation: Department of Medicine, University of Texas
Medical School, Houston, Texas.
Received October 29, 1996.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and ß
subunits in male rats. Proc Natl Acad Sci USA 83:4026–4029 subunits in superfused pituitary cell
cultures. Mol Cell Neurosci 2:277–283
and luteinizing hormone ß-subunit messenger ribonucleic acids in male
rats. Mol Endocrinol 1:834–838This article has been cited by other articles:
 |
|
 |
|
  H. Kanasaki, S. Mutiara, A. Oride, I. N. Purwana, and K. Miyazaki Pulse Frequency-Dependent Gonadotropin Gene Expression by Adenylate Cyclase-Activating Polypeptide 1 in Perifused Mouse Pituitary Gonadotroph LbetaT2 Cells Biol Reprod, September 1, 2009; 81(3): 465 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Thackray, J. L. Hunnicutt, A. K. Memon, Y. Ghochani, and P. L. Mellon Progesterone Inhibits Basal and Gonadotropin-Releasing Hormone Induction of Luteinizing Hormone {beta}-Subunit Gene Expression Endocrinology, May 1, 2009; 150(5): 2395 - 2403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J L Crawford, D A Heath, L J Haydon, B P Thomson, and D C Eckery Gene expression and secretion of LH and FSH in relation to gene expression of GnRH receptors in the brushtail possum (Trichosurus vulpecula) demonstrates highly conserved mechanisms Reproduction, January 1, 2009; 137(1): 129 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Ciccone, C. T. Lacza, M. Y. Hou, S. J. Gregory, K.-Y. Kam, S. Xu, and U. B. Kaiser A Composite Element that Binds Basic Helix Loop Helix and Basic Leucine Zipper Transcription Factors Is Important for Gonadotropin-Releasing Hormone Regulation of the Follicle-Stimulating Hormone {beta} Gene Mol. Endocrinol., August 1, 2008; 22(8): 1908 - 1923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Salisbury, A. K. Binder, and J. H. Nilson Welcoming {beta}-Catenin to the Gonadotropin-Releasing Hormone Transcriptional Network in Gonadotropes Mol. Endocrinol., June 1, 2008; 22(6): 1295 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Nicol, M-O Faure, J R McNeilly, J Fontaine, C Taragnat, and A S McNeilly Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in L{beta}T2 gonadotrophs J. Endocrinol., March 1, 2008; 196(3): 497 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Thackray and P. L. Mellon Synergistic Induction of Follicle-Stimulating Hormone {beta}-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smad Proteins Endocrinology, March 1, 2008; 149(3): 1091 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kowase, H. E. Walsh, D. S. Darling, and M. A. Shupnik Estrogen Enhances Gonadotropin-Releasing Hormone-Stimulated Transcription of the Luteinizing Hormone Subunit Promoters via Altered Expression of Stimulatory and Suppressive Transcription Factors Endocrinology, December 1, 2007; 148(12): 6083 - 6091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.A.M. Kuijper, C.B. Lambalk, D.I. Boomsma, S. van der Sluis, M.A. Blankenstein, E.J.C. de Geus, and D. Posthuma Heritability of reproductive hormones in adult male twins Hum. Reprod., August 1, 2007; 22(8): 2153 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zheng, M. Jimenez-Linan, B. S. Rubin, and L. M. Halvorson Anterior Pituitary Gene Expression with Reproductive Aging in the Female Rat Biol Reprod, June 1, 2007; 76(6): 1091 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Salisbury, A. K. Binder, J. C. Grammer, and J. H. Nilson Maximal Activity of the Luteinizing Hormone{beta}-Subunit Gene Requires {beta}-Catenin Mol. Endocrinol., April 1, 2007; 21(4): 963 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Akhter, B. W. Johnson, C. Crane, M. Iruthayanathan, Y.-H. Zhou, A. Kudo, and G. V. Childs Anterior Pituitary Leptin Expression Changes in Different Reproductive States: In Vitro Stimulation by Gonadotropin-releasing Hormone J. Histochem. Cytochem., February 1, 2007; 55(2): 151 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. McGillivray, V. G. Thackray, D. Coss, and P. L. Mellon Activin and Glucocorticoids Synergistically Activate Follicle-Stimulating Hormone {beta}-Subunit Gene Expression in the Immortalized L{beta}T2 Gonadotrope Cell Line Endocrinology, February 1, 2007; 148(2): 762 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Thackray, S. M. McGillivray, and P. L. Mellon Androgens, Progestins, and Glucocorticoids Induce Follicle-Stimulating Hormone {beta}-Subunit Gene Expression at the Level of the Gonadotrope Mol. Endocrinol., September 1, 2006; 20(9): 2062 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Senthilkumaran, S. Peterson, M. Taylor, and G. Bedecarrats Use of a vascular access port for the measurement of pulsatile luteinizing hormone in old broiler breeders. Poult. Sci., September 1, 2006; 85(9): 1632 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Galmiche, N. Richard, S. Corvaisier, and M.-L. Kottler The Expression of Aromatase in Gonadotropes Is Regulated by Estradiol and Gonadotropin-Releasing Hormone in a Manner that Differs from the Regulation of Luteinizing Hormone Endocrinology, September 1, 2006; 147(9): 4234 - 4244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Ferris and M. A. Shupnik Mechanisms for Pulsatile Regulation of the Gonadotropin Subunit Genes by GNRH1 Biol Reprod, June 1, 2006; 74(6): 993 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Lujan, A. A. Krzemien, R. L. Reid, and D. A. Van Vugt Developing a Model of Nutritional Amenorrhea in Rhesus Monkeys Endocrinology, January 1, 2006; 147(1): 483 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kanasaki, G. Y. Bedecarrats, K.-Y. Kam, S. Xu, and U. B. Kaiser Gonadotropin-Releasing Hormone Pulse Frequency-Dependent Activation of Extracellular Signal-Regulated Kinase Pathways in Perifused L{beta}T2 Cells Endocrinology, December 1, 2005; 146(12): 5503 - 5513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Coss, V. G. Thackray, C.-X. Deng, and P. L. Mellon Activin Regulates Luteinizing Hormone {beta}-Subunit Gene Expression through Smad-Binding and Homeobox Elements Mol. Endocrinol., October 1, 2005; 19(10): 2610 - 2623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Pask, H. Kanasaki, U. B. Kaiser, P. M. Conn, J. A. Janovick, D. W. Stockton, D. L. Hess, M. J. Justice, and R. R. Behringer A Novel Mouse Model of Hypogonadotrophic Hypogonadism: N-Ethyl-N-Nitrosourea-Induced Gonadotropin-Releasing Hormone Receptor Gene Mutation Mol. Endocrinol., April 1, 2005; 19(4): 972 - 981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall Regulation of gonadotropin subunit gene transcription J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu, X.-Z. Xu, C. S. Nunemaker, and S. M. Moenter Dose-Dependent Switch in Response of Gonadotropin-Releasing Hormone (GnRH) Neurons to GnRH Mediated through the Type I GnRH Receptor Endocrinology, February 1, 2004; 145(2): 728 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zapatero-Caballero, F. Sanchez-Franco, C. Fernandez-Mendez, M. Garcia-San Frutos, L. M. Botella-Cubells, and G. Fernandez-Vazquez Gonadotropin-Releasing Hormone Receptor Gene Expression During Pubertal Development of Female Rats Biol Reprod, February 1, 2004; 70(2): 348 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Y. Bedecarrats and U. B. Kaiser Differential Regulation of Gonadotropin Subunit Gene Promoter Activity by Pulsatile Gonadotropin-Releasing Hormone (GnRH) in Perifused L{beta}T2 Cells: Role of GnRH Receptor Concentration Endocrinology, May 1, 2003; 144(5): 1802 - 1811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zapatero-Caballero, F. Sanchez-Franco, N. Guerra-Perez, C. Fernandez-Mendez, and G. Fernandez-Vazquez Gonadotropin-Releasing Hormone Receptor Gene Expression During Pubertal Development of Male Rats Biol Reprod, May 1, 2003; 68(5): 1764 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. V. Vasilyev, M. A. Lawson, D. Dipaolo, N. J. G. Webster, and P. L. Mellon Different Signaling Pathways Control Acute Induction versus Long-Term Repression of LH{beta} Transcription by GnRH Endocrinology, September 1, 2002; 143(9): 3414 - 3426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Anand, S. Losee-Olson, F. W. Turek, and T. H. Horton Differential Regulation of Luteinizing Hormone and Follicle-Stimulating Hormone in Male Siberian Hamsters by Exposure to Females and Photoperiod Endocrinology, June 1, 2002; 143(6): 2178 - 2188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Curtin, S. Jenkins, N. Farmer, A. C. Anderson, D. J. Haisenleder, E. Rissman, E. M. Wilson, and M. A. Shupnik Androgen Suppression of GnRH-Stimulated Rat LH{beta} Gene Transcription Occurs Through Sp1 Sites in the Distal GnRH-Responsive Promoter Region Mol. Endocrinol., November 1, 2001; 15(11): 1906 - 1917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-L. Kottler, S. Chauvin, N. Lahlou, C. E. Harris, C. J. Johnston, J.-P. Lagarde, P. Bouchard, N. R. Farid, and R. Counis A New Compound Heterozygous Mutation of the Gonadotropin-Releasing Hormone Receptor (L314X, Q106R) in a Woman with Complete Hypogonadotropic Hypogonadism: Chronic Estrogen Administration Amplifies the Gonadotropin Defect J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3002 - 3008. [Abstract] [Full Text]
|
|
|
|
|
|
P. S. Nathwani, S. K. Kang, K. W. Cheng, K.-C. Choi, and P. C. K. Leung Regulation of Gonadotropin-Releasing Hormone and Its Receptor Gene Expression by 17{beta}-Estradiol in Cultured Human Granulosa-Luteal Cells Endocrinology, May 1, 2000; 141(5): 1754 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Weck, A. C. Anderson, S. Jenkins, P. C. Fallest, and M. A. Shupnik Divergent and Composite Gonadotropin-Releasing Hormone-Responsive Elements in the Rat Luteinizing Hormone Subunit Genes Mol. Endocrinol., April 1, 2000; 14(4): 472 - 485. [Abstract] [Full Text]
|
|
|
|
|
|
D. J. Bernard, I. Y. Merzlyak, T. H. Horton, and F. W. Turek Differential Regulation of Pituitary Gonadotropin Subunit Messenger Ribonucleic Acid Levels in Photostimulated Siberian Hamsters Biol Reprod, January 1, 2000; 62(1): 155 - 161. [Abstract] [Full Text]
|
|
|
|
|
|
G. Maya-Núñez and P. M. Conn Transcriptional Regulation of the Gonadotropin-Releasing Hormone Receptor Gene Is Mediated in Part by a Putative Repressor Element and by the Cyclic Adenosine 3',5'-Monophosphate Response Element Endocrinology, August 1, 1999; 140(8): 3452 - 3458. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. R. Norwitz, K.-H. Jeong, and W. W. Chin Molecular Mechanisms of Gonadotropin-Releasing Hormone Receptor Gene Regulation Reproductive Sciences, July 1, 1999; 6(4): 169 - 178. [Abstract] [PDF]
|
|
|
|
|
|
X. Lin and P. M. Conn Transcriptional Activation of Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH and Cyclic Adenosine Monophosphate Endocrinology, September 1, 1998; 139(9): 3896 - 3902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kamegai, T. G. Unterman, L. A. Frohman, and R. D. Kineman Hypothalamic/Pituitary-Axis of the Spontaneous Dwarf Rat: Autofeedback Regulation of Growth Hormone (GH) Includes Suppression of GH Releasing-Hormone Receptor Messenger Ribonucleic Acid Endocrinology, August 1, 1998; 139(8): 3554 - 3560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. B. Kaiser, E. Sabbagh, B. D. Saunders, and W. W. Chin Identification of cis-Acting Deoxyribonucleic Acid Elements That Mediate Gonadotropin-Releasing Hormone Stimulation of the Rat Luteinizing Hormone {beta}-Subunit Gene Endocrinology, May 1, 1998; 139(5): 2443 - 2451. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
