| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Division of Endocrinology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908
Address all correspondence and requests for reprints to: Dr. A. C. Dalkin, Division of Endocrinology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908. E-mail: acd6v{at}virginia.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, and ßB mRNAs, whereas the ßA mRNA was
not detected. In males, levels of FSHß and follistatin were higher
than those in females. After gonadectomy, levels of FSHß and
follistatin increased in both sexes, whereas ßB rose only in females.
In males, blockade of GnRH action from the time of castration prevented
the increase in FSHß and follistatin, suggesting that GnRH is the
primary stimulus for these gene products. In females, treatment with a
GnRH antagonist only partially prevented the rise in FSHß,
follistatin, and ßB expression, suggesting that other factors were
also important. Passive immunoneutralization of circulating inhibin
increased FSHß and follistatin (but not ßB), providing evidence
that inhibin is a physiological regulator of follistatin. Replacement
of estradiol at the time of ovariectomy prevented the increase in ßB
mRNA, suggesting that gonadal steroids may also act via local factors
to regulate FSHß. In summary, these studies provide evidence that
GnRH, gonadal steroids, and gonadal peptides probably regulate FSHß
expression at least in part via the intrapituitary activin/follistatin
system. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-subunit and hormone-specific LH
ß- and FSH ß-subunits) gene expression (for review, see Ref.2).
Gonadal steroids regulate GnRH secretion and also exert actions
directly on the pituitary to modulate gonadotropin subunit messenger
RNA (mRNA) concentrations (1, 2).
In addition to GnRH and gonadal steroids, FSHß mRNA expression and
FSH secretion are under the control of the peptide hormones inhibin,
activin, and follistatin (for reviews, see Refs. 3 and 4). Inhibins,
heteromeric dimers of an and either of two related ß (A or B)
chains, are produced primarily by the gonads, and in adult female rats
act to reduce FSH secretion. Activins, homo- or heteromeric dimers of
the ßA- and ßB-chains, are produced in a wide array of tissues and
stimulate FSH by actions on the gonadotrope cells. The structurally
unrelated follistatins suppress FSH via binding to and inactivation of
activin.
Inhibin, activin, and follistatin are present in the systemic circulation, but it is known that activin and follistatin are also produced in the pituitary gland by folliculo-stellate and gonadotrope cells (5, 6, 7, 8) and exert autocrine/paracrine regulation of FSH synthesis and secretion. Like the gonadotropin subunits, pituitary follistatin mRNA levels exhibit dynamic variation during the estrous cycle (9, 10), and both follistatin and ßB mRNAs increase after gonadectomy (5, 11, 12, 13). The physiological role of pituitary-derived activin B is supported by data showing that immunoneutralization of activin B in vitro (pituitary cells in culture) (14) or perifusion of dispersed pituitary cells to remove activin (15) results in reduced FSHß mRNA levels and FSH secretion. Thus, the local production of activin and follistatin appears to be an important mechanism regulating FSH and represents a potential site where hypothalamic or systemic endocrine signals may be integrated to effect changes in FSH synthesis and secretion. The purpose of the studies reported here was to develop sensitive assays for measurement of inhibin/activin subunit mRNAs (similar to our current methods for quantifying follistatin mRNA) within a single pituitary gland, to compare the expressions of these mRNAs in adult male and female animals, and to identify the relative contributions of hypothalamic GnRH and circulating inhibin in regulating the production of pituitary follistatin and activin mRNAs.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-directed antiserum (provided by Dr. Wylie Vale, La
Jolla, CA) was given in a regimen of 0.5 ml, iv (via indwelling
external jugular catheters), every 6 h (16). As quantities of the
anitsera are limited, we measured follistatin and ßB mRNA levels in
RNA samples from that previously reported experiment (16) with RNA
having been stored at -70 C. To define the contribution of GnRH, the
GnRH antagonist LRF-147 (provided by Dr. J. Stewart, Denver, CO) was
administered 30 µg, iv, every 8 h (the vehicle was 0.1%
BSA-0.9% normal saline) (17). To replace estradiol in gonadectomized
rats, sc SILASTIC brand implants (Dow Corning, Midland, MI) were used
to produce serum levels within the adult physiological range (18, 19). At the completion of experiments, animals were killed by decapitation, and pituitary glands were rapidly removed and snap-frozen in liquid nitrogen until RNA extraction (20). All animal protocols were approved by the University of Virginia animal research committee.
mRNA measurements
The methods for measuring FSHß mRNA (dot blot hybridization
assay) and follistatin mRNA (quantitative RT-PCR assay) were previously
reported (12, 20). To quantify the inhibin , ßA, and ßB mRNAs in
RNA from a single pituitary, we developed quantitative RT-PCR assays
for inhibin/activin subunits. Each assay was optimized for
Mg+2 concentration and annealing temperatures, and the
resultant assays were identical to that used for measurement of
follistatin in terms of reagents, RT and PCR parameters, (-)RT
controls for DNA contamination, and the method for calculation of mRNA
abundance. The complementary DNAs (cDNAs) used to create the
competitive templates (CT) were provided by Dr. K. Mayo (Northwestern
University, Evanston, IL). The CT cDNA constructs were produced as
follows.
For inhibin , the native cDNA was transferred into the expression
vector pSP64 polyadenylase [poly(A); Promega Corp., Madison, WI], and
a 310-bp DNA fragment (StuI/KpnI digest) was
replaced with a 502-bp DNA fragment (ApaI digest of pBR 322
plasmid). The oligonucleotide primers used for the assay were:
upstream, 5'-TTGGTCTCCT-GCAGCCTTGCGTTT-3' (bp 987-1011); and
downstream, 5'-GGAGGAGACGAGGT-GCTTTTAGAT-3' (bp 1384–1360). Thus, the
native mRNA-generated product is 397 bp, and the CT mRNA-generated
product is 589 bp with a GC content correction factor of 0.71 (12).
For ßA, the native cDNA was transferred into the expression vector pSP64 poly(A), and a 612-bp DNA fragment (HindIII/PstI digest) was replaced with a 783-bp DNA (HindIII/PstI digest of pBR 322 plasmid). The oligonucleotide primers used for the assay were: upstream, 5'-CACTTGAAGAAGAGACCCGATGTC-3' (bp 370–394); and downstream, 5'-TGAGGATGGTCTTCAGACTGCCTA-3' (bp 1079–1055). Thus, the native mRNA-generated product is 729 bp, and the CT mRNA-generated product is 890 bp with a GC content correction factor of 0.84.
For ßB, the native cDNA was transferred into the expression vector pSP64 poly(A) and a 170-bp DNA fragment (HincII/PstI digest) replaced with a 296-bp DNA (HincII/PstI digest of pBR 322 plasmid). The oligonucleotide primers used for the assay were: upstream, 5'-TCGCAGGACACCTGTACGTCGTGC-3' (bp 754–777); and downstream, 5'-GCCTTCGTTAGAGACGAAGAAGTA-3' (bp 1116–1092). Thus, the native mRNA-generated product is 362 bp, and the CT mRNA-generated product is 588 bp with a GC content correction factor of 0.65.
All mRNA concentrations are expressed as femtomoles of mRNA per 100
µg pituitary DNA to allow for comparison between mRNAs and to correct
for pituitary size. The intra- and interassay variabilities for these
assays were: inhibin , 6.1% (n = 3) and 14.0% (n = 5);
and ßB, 7.0% (n = 4) and 12.9% (n = 12),
respectively.
Statistical analysis
Treatment-induced effects were examined by one-way ANOVA.
Differences between groups were examined by Duncan’s multiple range
test.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, and ßB
mRNAs following gonadectomy in male and female rats (Fig. 1
) > follistatin. We were we not able to detect ßA mRNA
signal in either male or female animals, consistent with prior reports
using less sensitive methods (13). In intact male animals, levels of
FSHß and follistatin mRNAs were higher than those in females, whereas
inhibin and ßB mRNA concentrations were generally similar between
the sexes (i.e. FSHß:inhibin :ßB:follistatin: males,
3:1:1:0.3; females, 1:1:1:0.2). After gonadectomy, FSHß mRNA
expression increased in both sexes. However, in males, the increase in
FSHß (60%) was smaller than that in females (3-fold). Follistatin
increased by a similar degree (2-fold) in males and females. Of
interest, ßB mRNA expression was only increased after gonadectomy in
females, rising approximately 2-fold.
|
) and ßB
mRNAs were not measured in this study, as neither increased after
castration in males (Fig. 1
).\.
|
peptide before
death 12 h later (16). Control animals received nonimmune sheep
serum. No change in either FSHß or follistatin mRNA expression was
observed (data not shown), suggesting that circulating inhibin does not
regulate follistatin mRNA expression in adult male animals.\.
Exp IV: expression of FSHß, follistatin, and ßB mRNAs after
ovariectomy; regulation by GnRH (Fig. 3)
In light of prior data documenting more rapid changes in
FSHß expression after gonadectomy in females compared with males
(16), we studied the response to GnRH blockade at shorter intervals in
female animals. Female rats were ovariectomized, and some animals
received the GnRH antagonist LRF-147 from the time of surgery. Animals
were then killed 12 or 24 h later. Of note, levels of ßB mRNA in
intact animals were lower than those in our initial experiment (compare
with Fig. 1). Potentially, some degree of variation between groups of
animals may be expected, in that follistatin and FSHß mRNA
expressions vary at least 2- to 3-fold during the estrous cycle (2, 9, 10). However, ßB mRNA levels are more stable, and hence,
physiological variations may not adequately explain these differences.
Alternatively, for some experiments we used historic samples (16), and
some differences in absolute value may reflect longer term storage.
Although we do not have a proven explanation, each experiment reported
here included its own proper control group(s). FSHß, follistatin, and
ßB mRNAs rose within 12 h after ovariectomy and continued to
increase through 24 h. At the 12 h point, GnRH blockade was
only partially effective in preventing the increase in follistatin mRNA
expression, whereas FSHß and ßB mRNAs concentrations were
maintained at intact levels. In contrast, by 24 h, the levels of
all three mRNAs rose (FSHß, 1.5-fold; ßB and follistatin, 6-fold)
in antagonist-treated animals, suggesting that the loss of gonadal
factors after ovariectomy was an important determinant of FSHß and
particularly follistatin and ßB mRNA expression.
|
)
|
) and LHß mRNAs and serum LH and later partially prevented the
increase in FSHß mRNA and FSH secretion (19). This partial effect on
FSH synthesis and secretion compared with that on LH is probably
related to the loss of inhibin. To determine whether estradiol could
regulate ßB gene expression, we measured the ßB mRNA concentrations
in animals 24 h after ovariectomy in the presence or absence of
gonadal steroid replacement and GnRH blockade with LRF-147. Intact
animals served as controls. ßB mRNA expression was increased
(1.6-fold) after ovariectomy. Replacement with estradiol prevented the
increase in ßB mRNA expression, with values remaining at intact
levels. Addition of the GnRH antagonist did not further reduce ßB
mRNA levels. Taken together with the data displayed in Fig. 3, in which
GnRH blockade alone was only partially effective at preventing the rise
in ßB mRNA, our data strongly suggest that estradiol directly
inhibits ßB mRNA expression.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
mRNAs after
gonadectomy, although not all studies are in agreement (5, 9, 13).
Alternatively, activin action may be modulated via changes in
follistatin expression, as pituitary expression of follistatin mRNA
increases on proestrus (9) as well as after gonadectomy (11, 12). The
factors regulating pituitary follistatin production are only recently
becoming evident from both in vivo and in vitro
studies. Exogenous GnRH (12), activin (21, 22, 23, 24), and estradiol (11) may
increase follistatin mRNA expression, whereas, conversely, testosterone
(24) and follistatin itself [presumably via its inactivation of
activin (23)] reduce the follistatin mRNA concentration. The roles of
these factors, if any, in the dynamic pattern of follistatin expression
during proestrus are presently unknown.
The data reported here expand on these concepts and provide further
evidence that regulation of pituitary-derived activin is biologically
important. In pituitary RNA samples from intact male rats, the
abundance of FSHß and follistatin mRNAs is greater, and the ßB mRNA
concentration is similar to that found in pituitaries from females.
Although follistatin mRNA expression increases after gonadectomy to a
similar degree in both sexes, gender-related differences are also
apparent in this paradigm, as the increase in FSHß mRNA is of greater
magnitude in females, and ßB is only increased in female animals. Of
note, inhibin mRNA levels remained unchanged in both male and
female animals after gonadectomy, suggesting that changes in ßB gene
expression probably result in changes in activin (rather than inhibin)
production. These differences between male and female animals as well
as between mRNA species could result from different regulatory
responses to GnRH, gonadal steroids, and/or gonadal peptides. Hence, we
pursued additional experiments to examine these possibilities.
Androgens have been shown to increase FSHß mRNA expression via enhancement of mRNA stability (17), whereas GnRH primarily increases FSHß gene transcription (25). Although the mechanism(s) is uncertain, GnRH is also an important stimulus for follistatin mRNA expression in males (12). To investigate the role of follistatin mRNA expression after castration, we aimed to determine the relative contributions of GnRH and testosterone in regulating follistatin and FSHß mRNAs. Treatment with a GnRH antagonist completely prevented the increase in follistatin and FSHß mRNAs, suggesting that GnRH regulates both mRNAs in parallel. In the absence of GnRH, testosterone increased FSHß 2-fold [as has been reported (17)], and there was a tendency (although not statistically significant) for follistatin mRNA expression to decline. This trend would be consistent with a recent report that testosterone reduced follistatin expression in vitro (24), and the differing results may reflect the higher dose of testosterone (50 nM) used in the in vitro cell culture experiments. In light of our data revealing no change in either FSHß or follistatin mRNAs after passive immunoneutralization of inhibin in male animals, we conclude that the primary stimulus for these two genes is GnRH.
The intrapituitary regulation of FSHß gene expression in female animals, although similar in certain aspects to that in males, appears to be more complex. In females, the increase in FSHß mRNA is accompanied by an early increase in follistatin mRNA (within 12 h), and ßB mRNA is also increased at 12 h, a pattern that continues through 48 h after ovariectomy. This rapid increase in ßB differs from prior data in terms of the time course (7 days) over which mRNA changes are observed (13). When measuring low abundance mRNAs, the improved sensitivity achieved with quantitative RT-PCR assays compared with dot-blot hybridizations may account for this difference. The rise in ßB in females combined with a greater postgonadectomy rise in FSHß mRNA expression in female rats suggests that the change in local activin production is a more important factor in female rats.
Similar to males, GnRH antagonist-treated ovariectomized females had significantly lower levels of FSHß, follistatin, and ßB mRNAs than ovariectomized animals, which supports a central role of GnRH in the regulation of activin action in the gonadotrope. However, in contrast to males, GnRH blockade was only partially effective in limiting FSHß and follistatin mRNA expression in antagonist-treated animals, and mRNA concentrations were higher than those in intact animals. Of interest, despite parallel changes in FSHß, follistatin, and ßB mRNAs, the physiological regulation of these mRNAs appears distinct. In agreement with our previous report, immunoneutralization of circulating inhibin increased FSHß (16), and follistatin mRNA was also increased after inhibin immunoneutralization. In contrast, ßB mRNA levels do not appear to be regulated by circulating inhibin.
Prior data potentially linking inhibin to suppression of pituitary follistatin mRNA have been reported. Bilezikjian et al. observed that in primary culture, inhibin reduced follistatin mRNA levels within 2 h and by 80% at 24 h (24). In that report, a small (10–20%) reduction in ßB mRNA was noted after inhibin treatment, although this was only seen at the highest inhibin concentration (100 pM) examined. Our data support a physiological role for inhibin regulation of follistatin expression in female rats, and in light of the absence of changes in ßB mRNA, suggest that this relationship is independent of changes in pituitary-derived activin. During the estrous cycle, pituitary follistatin mRNA expression and follistatin content increase late on the day of proestrus (9, 10). Although this may in part reflect increased GnRH secretion, a decline in circulating inhibin levels has been shown to either precede (26) or coincide with (27) the time at which follistatin increases. Therefore, we hypothesize that in cycling animals the preovulatory reduction in circulating inhibin, ultimately responsible for the secondary FSH surge (28), additionally results in increased follistatin, which may, in turn, limit further FSH synthesis and secretion.
ßB mRNA levels increase after ovariectomy despite blockade of GnRH
action and appear to be independent of changes in circulating inhibin.
These data suggest that other ovarian factors are probably inhibiting
expression of the ßB gene in the intact animal. The likely candidate
is estradiol, as prior studies have shown that treatment of female
animals from the time of ovariectomy prevents the rise in ßB
expression (5). Our data showing that replacement of estradiol from the
time of ovariectomy is more effective than GnRH blockade in preventing
the rise in ßB (compare Fig. 5 to Fig. 3) suggest that estradiol
could act directly at the pituitary independently of GnRH. Indeed, the
combination of GnRH blockade with estradiol replacement was no more
effective at inhibiting ßB expression than was replacement with
estradiol alone. If this relationship is indeed true, prior reports
suggesting that ßB mRNA levels do not change during proestrus (9)
could reflect a relative balance between increasing GnRH stimulation
and rising plasma estradiol, thereby resulting in stable ßB
expression. Further studies are currently underway in our laboratory to
determine the relative contributions of estradiol and GnRH on ßB mRNA
expression during the estrous cycle.
In summary, regulation of the local pituitary activin/follistatin response system appears to be an important part of control of FSH synthesis and, hence, reproductive function. In both male and female rats, GnRH appears to be the primary factor controlling the expression of follistatin and FSHß expression. Although pituitary-derived activin may be found in both sexes, GnRH only appears to increase ßB expression in female animals. Gonadal peptides may serve to modify GnRH action. Although circulating levels of inhibin are low in adult male rats and appear to be of little importance (29), in females circulating inhibin exerts an inhibitory tone on both FSHß and follistatin expression. For ßB, estradiol may serve as the primary inhibitory factor. In summary, FSH synthesis appears to be regulated by both stimulatory and inhibitory mechanisms in males and females. The final pathway involved in the regulation of FSHß mRNA expression appears to involve the intrapituitary expression of follistatin, with activin and peripheral inhibin playing major roles in females.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received January 14, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and LH ß mRNA quantitation in the anterior
pituitary of castrate male and female rats using an optimized dot-blot
hybridization assay. Endocrinology 119:691–698[Abstract]
This article has been cited by other articles:
 |
|
 |
|
  L. L. Burger, D. J. Haisenleder, G. M. Wotton, K. W. Aylor, A. C. Dalkin, and J. C. Marshall The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E277 - E285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M Bilezikjian, A. L Blount, C. J Donaldson, and W. W Vale Pituitary actions of ligands of the TGF-{beta} family: activins and inhibins. Reproduction, August 1, 2006; 132(2): 207 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T M Lovell, P G Knight, and R T Gladwell Variation in pituitary expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and type-I and type-II activin receptors during the chicken ovulatory cycle J. Endocrinol., September 1, 2005; 186(3): 447 - 455. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 T. J. Spady, R. Shayya, V. G. Thackray, L. Ehrensberger, J. S. Bailey, and P. L. Mellon Androgen Regulates Follicle-Stimulating Hormone {beta} Gene Expression in an Activin-Dependent Manner in Immortalized Gonadotropes Mol. Endocrinol., April 1, 2004; 18(4): 925 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Prendergast, L. L. Burger, K. W. Aylor, D. J. Haisenleder, A. C. Dalkin, and J. C. Marshall Pituitary Follistatin Gene Expression in Female Rats: Evidence That Inhibin Regulates Transcription Biol Reprod, February 1, 2004; 70(2): 364 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Burger, D. J. Haisenleder, K. W. Aylor, A. C. Dalkin, K. A Prendergast, and J. C. Marshall Regulation of Luteinizing Hormone-{beta} and Follicle-Stimulating Hormone (FSH)-{beta} Gene Transcription by Androgens: Testosterone Directly Stimulates FSH-{beta} Transcription Independent from Its Role on Follistatin Gene Expression Endocrinology, January 1, 2004; 145(1): 71 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Burger, A. C. Dalkin, K. W. Aylor, D. J. Haisenleder, and J. C. Marshall GnRH Pulse Frequency Modulation of Gonadotropin Subunit Gene Transcription in Normal Gonadotropes--Assessment by Primary Transcript Assay Provides Evidence for Roles of GnRH and Follistatin Endocrinology, September 1, 2002; 143(9): 3243 - 3249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kawakami, Y. Fujii, Y. Okada, and S. J. Winters Paracrine Regulation of FSH by Follistatin in Folliculostellate Cell-Enriched Primate Pituitary Cell Cultures Endocrinology, June 1, 2002; 143(6): 2250 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. Chen, H. M. Lui, S.-L. Lin, J. M. Lee, and S.-Y. Ying Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis by Activin Experimental Biology and Medicine, February 1, 2002; 227(2): 75 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Burger, A. C. Dalkin, K. W. Aylor, L. J. Workman, D. J. Haisenleder, and J. C. Marshall Regulation of Gonadotropin Subunit Transcription after Ovariectomy in the Rat: Measurement of Subunit Primary Transcripts Reveals Differential Roles of GnRH and Inhibin Endocrinology, August 1, 2001; 142(8): 3435 - 3442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Winters, S. Kawakami, A. Sahu, and T. M. Plant Pituitary Follistatin and Activin Gene Expression, and the Testicular Regulation of FSH in the Adult Rhesus Monkey (Macaca mulatta) Endocrinology, July 1, 2001; 142(7): 2874 - 2878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Baratta, L.A. West, A.M. Turzillo, and T.M. Nett Activin Modulates Differential Effects of Estradiol on Synthesis and Secretion of Follicle-Stimulating Hormone in Ovine Pituitary Cells Biol Reprod, February 1, 2001; 64(2): 714 - 719. [Abstract] [Full Text]
|
|
|
|
|
|
A. C. Dalkin, D. J. Haisenleder, J. T. Gilrain, K. Aylor, M. Yasin, and J. C. Marshall Gonadotropin-Releasing Hormone Regulation of Gonadotropin Subunit Gene Expression in Female Rats: Actions on Follicle-Stimulating Hormone {beta} Messenger Ribonucleic Acid (mRNA) Involve Differential Expression of Pituitary Activin ({beta}-B) and Follistatin mRNAs Endocrinology, February 1, 1999; 140(2): 903 - 908. [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 |
