| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Imperial College of Science, Technology and Medicine Endocrine Unit, Hammersmith Hospital, London W12 ONN, United Kingdom
Address all correspondence and requests for reprints to: Professor S. R. Bloom, ICSM Endocrine Unit, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom. E-mail: sbloom{at}rpms.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
A pituitary-specific galanin receptor, originally designated GAL-R23, has been characterized in rat anterior pituitary membranes, although the cell types expressing this receptor have yet to be established (5). At this receptor, the C-terminal part of the peptide is crucial for receptor binding and biological activity. Hence, galanin 1–29 and the fragment 3–29 have similar activity, but the fragment 1–15 is ineffective. This is in contrast to the gut/brain receptor, or GAL-R1, at which the N-terminus is essential for receptor binding with galanin 1–29 and for the fragment 1–15 being active and galanin 3–29 inactive (6). Furthermore, the effect of galanin on PRL secretion has been shown to be mediated via the pituitary-specific GAL-R2 (5, 7). The recent cloning of a further galanin receptor in the rat hypothalamus and brain, which has also been called the GAL-R2, has lead to some confusion regarding the nomenclature of the galanin receptors. Although this latter receptor has only 38% homology to the rat GAL-R1, it has a similar pharmacological profile to the GAL-R1, except for a 10-fold lower affinity for both human galanin and galanin 1–16 (8, 9). This GAL-R2 is expressed in small amounts in the anterior pituitary gland; however, it does not bind galanin 3–29 (9). For the purposes of this paper, we will refer to the first described GAL-R2 (the pituitary-specific galanin receptor at which the fragment 3–29 is active and the fragment 1–15 is inactive) as GAL-R2 (orig.).
Estrogen, an essential modulator of reproductive function, regulates both gonadotrophs and lactotrophs; and elevated levels of estrogen facilitate the proestrous gonadotrophin surge, at least in part, by increasing the number of gonadotrophs responding to LHRH (10). Pituitary galanin expression and release are stimulated by estrogen (2). It is colocalized to the lactotrophs, which are in close association with gonadotrophs in the dorso-cephalic region of the anterior pituitary gland (11, 12). We have now investigated the hypothesis that pituitary galanin may act as a paracrine regulator of gonadotroph function.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Animals and tissues
Adult female Wistar rats (Interfauna, Huntingdon, UK), weighing
200–250 g, were housed in wire-bottomed cages with ad
libitum access to food and water. Anterior pituitaries were
harvested from rats at different stages of the estrous cycle, as
determined by microscopic examination of serial vaginal smears. The
experiments performed at proestrus were harvested during the afternoon,
which we consider as the time immediately after the LH surge. Animals
were killed by CO2 asphyxiation, and the anterior
pituitaries were rapidly removed and used immediately for pituitary
dispersion or perifusion.
Pituitary dispersion
Pituitary glands were rapidly removed, dissected free of the
neurointermediate lobes, and placed in cold DMEM with 0.11 g/liter
sodium pyruvate, 4.5 g/liter glucose, 100 IU/ml penicillin, 100 µg/ml
streptomycin, 0.3% BSA, and 5 g/liter HEPES (pH 7.4). The anterior
pituitaries were then dispersed using a method adapted from Childs
et al. (14). Briefly, they were washed in DMEM and then
placed in DMEM containing 3 mg/ml trypsin with 250 µg/ml
deoxyribonuclease I (type IV). Incubation for 15 min in a
shaking water bath (140 strokes/min, 37 C) was followed by
centrifugation (500 x g, 5 min) and resuspension in
DMEM containing 250 µg/ml deoxyribonuclease I and trypsin inhibitor
(1 mg/ml), as previously described (15). Fragments were triturated, and
the remaining pieces were allowed to settle. The freshly dispersed
material in the supernatant was removed, and the procedure was repeated
until all the fragments had been dissociated. The cells were then
centrifuged at 500 x g for 5 min, and the pellet was
resuspended in serum-free primary cell culture medium (BME medium, Life
Sciences Technology, Paisley, UK) containing 100 IU/ml
penicillin, 100 µg/ml streptomycin, 2.5 µg/ml fungizone, 40 µg/ml
gentamycin, 20 mM L-glutamine, 26
mM NaHCO3 and was buffered with 25
mM HEPES (pH 7.4). The cells were filtered through a
70-µm nylon mesh (Falcon, Franklin Lakes, NJ); and cell
viability, determined by trypan blue exclusion, was routinely more than
90%. The average yield per pituitary was 2.0 ± 0.5 x
106 cells. Monodispersed cells (2.5 x
105, determined by hemocytometer counts) were plated out in
sterile 48-well plates coated with sterile poly-L-lysine
(0.1 mg/ml). The cells were allowed to attach to the wells of the
culture plate for 3 h, after which time, the medium was aspirated
and replaced with 1 ml of primary cell culture medium containing 10%
FBS (heat inactivated). The cells were maintained at 37 C with 5%
CO2-95% air for a 48-h recovery period.
Secretion experiments
Cells were washed twice in 1 ml DMEM containing 0.1% BSA. After
a 2-h preincubation, the medium was removed and replaced with 500 µl
of medium plus the appropriate test substance, 0.1 nM-1
µM pGal 1–29 or rGal 1–29, with or without 100
nM LHRH, for 4 h. At the end of the incubation period,
medium was removed and frozen at -20 C.
Anterior pituitary fragment perifusion
Rat anterior pituitaries were perifused as previously described
(16). Briefly, anterior pituitaries from female Wistar rats were
harvested during the afternoon of proestrus, and each pituitary was cut
into eight pieces. Sixteen pieces, randomly taken from the total pool
of 64 pieces, were perifused in each isolated chamber, containing
0.3 g Bio-Gel P2 (Bio-Rad Laboratories,
Richmond, CA) as extracellular support. The perifusion medium was DMEM
with 0.11 g/liter sodium pyruvate, 4.5 g/liter glucose, 0.5% BSA, 50
mg/liter ascorbic acid, and 50,000 KIU/liter aprotinin (Trasylol R,
Bayer, Haywards Heath, UK), and it was constantly gassed with 5%
CO2-95% O2 at pH 7.4. The chambers were
immersed in a water bath at 37 C, and each was perifused with medium at
a flow rate of 0.15 ml/min-1. Fractions of 0.5 ml were
collected every 3 min and immediately frozen until hormone assay. The
effects of the test substances were compared in all the experiments
with a paired control chamber perifused with control medium alone. Each
perifusion study was replicated 4 times.
Experimental protocols
Effect of exogenous galanin and galanin fragments. The
perifusion system was used to assess the effects of exogenous pGal and
its fragments on LH and FSH secretion. After an initial 90-min
equilibration period with culture medium, perifusate collection was
begun. This was denoted: time zero. pGal 1–29 or its fragments (pGal
3–29 and 1–15) were dissolved in the medium (at a concentration range
of 0.1 nM to 1 µM) immediately before use and
were added to the system from 30–170 min. At 90 min (60 min after
initiation of the test substances), a 20-min pulse of 100
nM LHRH was applied to each perifusion chamber. The dose
was determined from previous experiments in which 100 nM
LHRH was effective and reproducible. The test substance was
administered for a further hour after cessation of the LHRH pulse,
until 170 min. The experiment ended with a further 60-min baseline with
control medium, and the viability of the cells was verified by a 5-min
pulse of 56 mM KCl at 230 min.
Effect of endogenous galanin. The perifusion system was used to assess the effects of endogenous galanin on LH and FSH release. The time course of medium changes was the same as that employed in the protocol (under Effect of exogenous galanin and galanin fragments) above. Gas was raised in rabbit and was C-terminally directed. The Gas showed excellent affinity for galanin, such that diluted antisera (1:100) incubated with 125I-labeled pGal at 37 C for 4 h, bound 86% of the labeled peptide. Either perifusion medium alone or that containing 1:100 dilution of Gas or containing nonimmune rabbit serum (Nias) was administered to the chambers from 30–170 min with a 20-min pulse of 100 nM LHRH given at 90 min.
Gonadotrophin determination
LH and FSH levels in the culture medium were measured using the
reagents and methods provided by the NIDDK and the National Hormone and
Pituitary Program (Dr. A. Parlow, Harbor University of CA, Los Angeles
Medical Centre). A double-antibody separation system was employed,
which used a goat antirabbit solid-phase antibody (Pharmacia and
Upjohn, Milton Keynes, UK) and 0.1% Triton-X100. Results were
calculated in terms of NIDDK standard preparation (NIDDK rat LH and FSH
ß-subunit).
Statistics
Results are shown as mean values ± SEM. Data
from the LH and FSH assays were compared by ANOVA, with subsequent
post hoc Tukey’s tests (Systat, Evanston, IL) between
control and experimental groups. For comparison of rates of LH and FSH
release in the perifusion studies, the area under the curve (AUC) for
each variable was calculated using the trapezoidal rule. The data were
analyzed by ANOVA with post hoc Tukey’s test. In all cases,
P < 0.05 was considered to be statistically
significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, A and B). pGal 1–29, at
concentrations of 1 nM, 100 nM, and 1
µM had no effect on basal LH release (control 2.9 ±
0.2 vs. pGal 1 µM 3.1 ± 0.3
ng/ml-1·4 h, n = 6) or FSH release (control
5.5 ± 0.5 vs. pGal 1 µM 5.8 ± 0.8
ng/ml-1·4 h, n = 6).
|
). pGal 1–29 also significantly
inhibited 100 nM LHRH-stimulated FSH release from dispersed
pituitaries harvested at proestrus. The basal production of FSH was
5.5 ± 0.5 ng/ml-1·4 h. LHRH (100 nM)
stimulated FSH release to 19.6 ± 3.1 ng/ml-1·4 h,
pGal (1 µM) attenuated LHRH (100
nM)-stimulated FSH release to 9.1 ± 1.6
ng/ml-1·4 h, i.e. 53% reduction,
P < 0.02; n = 6) (Fig. 2B). In addition, rGal
1–29 [which, compared with porcine, has three amino acid
substitutions at positions 23, 26, and 29 (17)] had a similar effect
to pGal in attenuating LHRH-stimulated LH release. LHRH (100
nM)-stimulated LH release from a basal level of 2.9 ±
0.3 ng/ml-1·4 h to 9.7 ± 0.9
ng/ml-1·4 h. rGal (0.1 nM) failed to
significantly alter LHRH (100 nM)-stimulated LH release
(9.3 ± 0.5 ng/ml-1·4 h, P = 0.95).
However, rGal (10 nM, 100 nM, and 1
µM) significantly attenuated LHRH (100
nM)-stimulated LH release (7.9 ± 0.4,
P < 0.05; 7.4 ± 0.2, P < 0.05;
6.4 ± 0.7 ng/ml-1·4 h, P < 0.05,
respectively; n = 4). Similarly, FSH release was attenuated. LHRH
(100 nM)-stimulated FSH release from a basal level of
5.5 ± 0.7 ng/ml-1· 4 h to 17.0 ± 2.3
ng/ml-1· 4 h. rGal (0.1 nM and 10
nM) failed to significantly alter LHRH (100
nM)-stimulated LH release (17.3 ± 0.7,
P = 0.98, 13.4 ± 0.8 ng/ml-1·4 h,
P = 0.97, respectively). However, rGal, 100
nM and 1 µM significantly attenuated LHRH
(100 nM)-stimulated FSH release (10.1 ± 1.0,
P < 0.05, 6.27 ± 0.6, P < 0.02,
ng/ml-1·4 h, respectively; n = 4). Neither pGal
(Table 1) nor rGal had an inhibitory
effect on stimulated LH or FSH release at other stages of the estrous
cycle.
|
|
).
However, pGal 1–29 significantly attenuated the LHRH-stimulated LH
release. pGal at 10 nM and 1 µM reduced the
stimulated LH release by 75% (AUC, 90–230 min, 179 ± 90
ng/min·ml-1 vs. control 713 ± 149
ng/min·ml-1, P < 0.02) and 80% (AUC,
90–230 min, 131 ± 7 ng/min·ml-1 vs.
control, P < 0.02, F = 14.6), respectively. pGal
1–29 at a dose of 0.1 nM did not significantly inhibit the
stimulated LH release (AUC, 90–230 min, 455 ± 25
ng/min·ml-1 vs. control, P =
0.28) (n = 4).
|
Effect of pGal fragments 3–29 and 1–15 on LH release. Basal
LH release again matched that from the untreated chambers before and
after addition of all the galanin fragments tested (AUC, 30–90 min,
control, -0.7 ± 1.1 ng/min·ml-1 vs.
pGal 1–29, -0.8 ± 1.5 ng/min·ml-1; pGal 3–29,
-0.5 ± 2.5 ng/min·ml-1; pGal 1–15, -0.9 ±
2.8 ng/min·ml-1) (Figure 4). Both full-length pGal 1–29 (1
µM) and the fragment, pGal 3–29 (1 µM),
significantly reduced the LHRH-stimulated release of LH, by 70% (AUC,
90–230 min, 206 ± 44 ng/min·ml-1 vs.
control 642 ± 77 ng/min·ml-1, P <
0.02) and 53% (AUC, 90–230 min, 310 ± 19 ng/min·ml-1vs. control, P < 0.02, F =
12.8), respectively. pGal 1–15 did not significantly inhibit the
LHRH-stimulated LH release (AUC, 90–230 min, 700 ± 101
ng/min·ml-1 vs. control, P =
0.88) (Fig. 4) (n = 4).
|
Effects of immunoblockade of endogenous galanin LH release.
Basal LH release matched that from the untreated chambers before and
after addition of Nias. Although the basal LH release in
the Gas-treated chamber was slightly higher than the other
chambers, addition of Gas did not alter basal LH secretion
(AUC, 30–90 min, untreated chamber, 0.8 ± 0.05
ng/min·ml-1 vs. Gas, 1.0 ±
0.7 ng/min·ml-1; Nias, -0.2 ± 0.2
ng/min·ml-1) (Fig. 5). The
rise in LH in response to LHRH in the NIas-treated chamber
was not significantly different from that of control (AUC, 90–230 min,
545 ± 46 ng/min·ml-1 vs. control,
489 ± 33 ng/min·ml-1, P = 0.23).
Gas potentiated the LHRH-stimulated release of LH by 48%
(AUC, 90–230 min, 721 ± 65 vs. control and
NIas, 489 ± 33 ng/min·ml-1 and
545 ± 46 ng/min·ml-1, respectively,
P < 0.05, F = 14.5) (n = 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
We have demonstrated in these experiments that galanin caused a dose-dependent inhibition of the LHRH-stimulated LH and FSH secretion in dispersed anterior pituitary cells and perifused pituitary fragments harvested during the afternoon of proestrus but had no effect on basal LH or FSH release. Galanin had no effect at other stages of the estrous cycle. We have also demonstrated that immunoblockade with specific galanin antiserum can augment LHRH-stimulated LH and FSH release at proestrus. Both pGal 1–29 and the specific GAL-R2(orig.) agonist, pGal 3–29, were capable of producing the inhibitory effect on gonadotrophin release, whereas the fragment pGal 1–15, a specific agonist of both the cloned GAL-R1 and GALR2, was without effect. This suggests that the effects are mediated by the pituitary-specific GAL-R2(orig.) receptor (5).
The inhibitory effects of galanin were maintained in dispersed anterior pituitary cells harvested at proestrus, even after 48 h of culture. It is known that the in vitro LH responses to LHRH-stimulation changes markedly during the estrous cycle, similar to those observed in vivo (23). The pituitary is most responsive to LHRH at proestrus, with an attenuated response at both estrus and diestrus. Our results confirm these observations. In dispersed anterior pituitary cells harvested at proestrus the LHRH-stimulated LH and FSH release was 10.7 and 19.6 (ng/ml), respectively, compared with 6.1 and 4.6 (ng/ml), respectively, at diestrus. Thus, it would seem that tissue cultures do remain permanently altered and retain their characteristics, even after 48 h of culture. Furthermore, in the perifusion experiments, which were performed immediately after sacrifice of the animal, we have observed effects similar to those seen in dispersed anterior pituitary cells, although the inhibitory effect of galanin was somewhat more pronounced in the pituitary fragments. This may reflect the fact that the pituitary architecture and paracrine communications remain intact.
Neuropeptides, synthesized within the anterior pituitary gland, may have a role in local regulation of function and have been claimed to provide fine tuning within the gland (24, 25). Pituitary galanin is produced by the lactotroph, and it stimulates PRL secretion (5, 7). Previously, it has been demonstrated that locally secreted pituitary galanin mediates the effects of estrogen on PRL release and lactotroph proliferation (7). Galanin-immunoneutralization inhibits basal and estrogen-stimulated PRL release from dispersed rat anterior pituitary cells and completely abolishes the reported mitogenic effects of estrogen on the lactotroph. Hyperestrogenization increases the number of galanin-secreting lactotrophs, and the resulting increase in basal PRL is completely abolished by treatment with galanin antiserum (7). These findings provide some evidence that locally synthesized pituitary galanin could act as a paracrine regulator of lactotroph function.
Pituitary architecture is well preserved in higher vertebrates, supporting the idea that local interaction between cells is of functional importance (24). Lactotrophs and gonadotrophs are found in close association with each other, and many of the lactotrophs are cup shaped and surround a gonadotroph (12). Adherent junctions between the lactotrophs and gonadotrophs have been reported, further suggesting a functional relationship between these cell types (11). A paracrine interaction between lactotrophs and gonadotrophs has been implied by studies on coaggregates of semipurified populations of gonadotrophs and lactotrophs, but the factors involved have not been identified (26). When medium that previously has been used to culture a gonadotroph-rich population is removed and then used to incubate a lactotroph-enriched/gonadotroph-poor population of rat anterior pituitary cells, PRL secretion is increased 2-fold, implying that the gonadotrophs secrete a PRL-releasing factor into the medium (26).
This present study provides some evidence for a physiological role for galanin, synthesized within the anterior pituitary, in regulating gonadotrophin release, because blockade of endogenous galanin in vitro, in perifused pituitary fragments harvested at proestrus, potentiates LHRH-stimulated LH and FSH release. However, this is in contrast with the in vivo findings of Lopez et al. (22), who found that iv administration of galanin antiserum at proestrus attenuated the LH surge but did not significantly alter plasma FSH concentration. These effects could suggest a divergent role for hypothalamic and pituitary galanin in the control of the gonadotroph. It is possible that these two systems interact, in an important temporal relationship, to fine tune pituitary gonadotroph function.
The fact that galanin was without effect at the other stages of the estrous cycle is not altogether surprising, because both in vivo and in vitro studies have demonstrated that the modulatory effects of some neuropeptides are estrous cycle- dependent (16, 27). Bauer-Dantion et al. (16, 27) have suggested that the facilitatory actions of neuropeptide Y are dependent on the endocrine milieu at the time of the LH surge. Furthermore, Kalra et al. (28) have demonstrated that a single intracerebroventricular injection of neuropeptide Y has either a stimulatory or inhibitory effect, depending on the sex hormone environment.
The changes in circulating gonadotrophin concentrations throughout the estrous cycle, especially at the preovulatory surge, can be accounted for by attendant patterns of ovarian estrogen secretion and its negative and positive feedback actions on gonadotrophin release (29, 10). The relative importance of the hypothalamus and pituitary as sites for this dual feedback regulation remains unclear. Using a reverse hemolytic plaque assay and cultured pituitary cells, it has been shown that estrogen recruits gonadotrophs to secrete LH, in response to LHRH, confirming a direct effect of estrogen on the anterior pituitary (30, 10). However, the mechanisms involved in the biphasic pattern of estrogen feedback during the estrous cycle remain to be elucidated.
Our findings suggest that pituitary galanin, acting as a paracrine agent via the GAL-R2(orig.), modulates gonadotrophin release and may play a role in the regulation and limitation of the preovulatory gonadotrophin surge. Estrogen levels peak at proestrus, inducing a 30-fold rise in pituitary galanin synthesis (2). However, there is evidence to suggest time delay between these two events (2, 31) such that the estrogen levels rise, first facilitating the preovulatory LH surge, and the subsequent rise in pituitary galanin may serve to limit this. Alternatively, it is possible that pituitary galanin plays a dampening role at proestrus and regulates the pituitary response to the increased LHRH pulse amplitude and frequency. Therefore, the paracrine inhibition of the gonadotroph, by pituitary galanin, may form an important part of the feedback loop regulating the reproductive axis.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
3 GAL-R2 refers to the recently cloned galanin
receptor in (8 9 ) and GAL-R2(orig.) refers to the originally
characterized galanin receptor in rat anterior pituitary membranes
(5 ).
Received March 12, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
TSH
cells. Endocrinology 137:1–9[CrossRef][Medline]
This article has been cited by other articles:
 |
|
 |
|
  A. G. Stoyanovitch, M. A. Johnson, D. K. Clifton, R. A. Steiner, and G. S. Fraley Galanin-Like Peptide Rescues Reproductive Function in the Diabetic Rat Diabetes, August 1, 2005; 54(8): 2471 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J Winters and J. P Moore Intra-pituitary regulation of gonadotrophs in male rodents and primates Reproduction, July 1, 2004; 128(1): 13 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kuriyama, S. Takekoshi, K. Tojo, Y. Nakai, M. J. Kuhar, and R. Y. Osamura Cocaine- and Amphetamine-Regulated Transcript Peptide in the Rat Anterior Pituitary Gland Is Localized in Gonadotrophs and Suppresses Prolactin Secretion Endocrinology, May 1, 2004; 145(5): 2542 - 2550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Seth, S. Stanley, P. Jethwa, J. Gardiner, M. Ghatei, and S. Bloom Galanin-Like Peptide Stimulates the Release of Gonadotropin-Releasing Hormone in Vitro and May Mediate the Effects of Leptin on the Hypothalamo-Pituitary-Gonadal Axis Endocrinology, February 1, 2004; 145(2): 743 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Q. Wang, R. Yuan, Y.-P. Sun, T.-J. Lee, and G. V. Shah Antiproliferative Action of Calcitonin on Lactotrophs of the Rat Anterior Pituitary Gland: Evidence for the Involvement of Transforming Growth Factor {beta}1 in Calcitonin Action Endocrinology, May 1, 2003; 144(5): 2164 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Splett, J. R. Scheffen, J. A. Desotelle, V. Plamann, and A. C. Bauer-Dantoin Galanin Enhancement of Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone Secretion in Female Rats Is Estrogen Dependent Endocrinology, February 1, 2003; 144(2): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Scheffen, C. L. Splett, J. A. Desotelle, and A. C. Bauer-Dantoin Testosterone-Dependent Effects of Galanin on Pituitary Luteinizing Hormone Secretion in Male Rats Biol Reprod, February 1, 2003; 68(2): 363 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Russell, C. J. Small, A. R. Kennedy, S. A. Stanley, A. Seth, K. G. Murphy, S. Taheri, M. A. Ghatei, and S. R. Bloom Orexin A Interactions in the Hypothalamo-Pituitary Gonadal Axis Endocrinology, December 1, 2001; 142(12): 5294 - 5302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Ward, C. J. Small, K. G. Murphy, A. R. Kennedy, M. A. Ghatei, and S. R. Bloom The Actions of Tuberoinfundibular Peptide on the Hypothalamo-Pituitary Axes Endocrinology, August 1, 2001; 142(8): 3451 - 3456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Small, M. S. Kim, S. A. Stanley, J. R.D. Mitchell, K. Murphy, D. G.A. Morgan, M. A. Ghatei, and S. R. Bloom Effects of Chronic Central Nervous System Administration of Agouti-Related Protein in Pair-Fed Animals Diabetes, February 1, 2001; 50(2): 248 - 254. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. R. Williams Cloning and Characterization of Two Novel Thyroid Hormone Receptor beta Isoforms Mol. Cell. Biol., November 15, 2000; 20(22): 8329 - 8342. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Schwartz Intercellular Communication in the Anterior Pituitary Endocr. Rev., October 1, 2000; 21(5): 488 - 513. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. F. Todd, C. M. B. Edwards, M. A. Ghatei, and S. R. Bloom The differential effects of galanin-(1---30) and -(3---30) on anterior pituitary hormone secretion in vivo in humans Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E1060 - E1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Invitti, F. P. Giraldi, A. Dubini, P. Moroni, M. Losa, R. Piccoletti, and F. Cavagnini Galanin Is Released by Adrenocorticotropin-Secreting Pituitary Adenomas in Vivo and in Vitro J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1351 - 1356. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
, 0.1
nM pGal; 
, 10 nM pGal; •, 1
µM pGal). Results are presented as means ±
SEM of four experiments.
, Gas 1:100;